PREFACE heavy and light lines, the heavy lines representing double bonds. This is in accordance with a plan originally proposed by one of the authors.' The two colored charts, taken in conjunction with Chapter XXXIV (a brief outline for the identification of organic sub- stances), should serve, to some extent, the purposes of a review. A number of charts throughout the text, illustrating the uses of a few important chemicals, have been incorporated if only to give the student some idea of the many and diverse uses to which organic substances may be put. In the opinion of the authors, the student should at the very outset be given some opportunity for collateral reading; hence, the references at the end of chapters and the general references at the end of the book. The glossary has been added to explain a number of medical terms used in the text. Photographs of a few of the outstanding leaders in organic chemistry have been included. The authors have freely consulted various text-books and journals and they wish to acknowledge their debt to the men responsible for the texts and articles. For their kindness in giving permission to reproduce diagrams, the authors wish to thank the following: The Marland Oil Co. (Petroleum Refining); R. F. Remler of the Mellon Institute of Industrial Research, and the National Wood Chemical Associ- ation (Uses of Methanol, Uses of Acetic Acid, Uses of Acetone, Uses of Formaldehyde); The U. S. Industrial Alcohol Co. (Ethyl Alcohol); D. Van Nostrand Co. (two colored charts); and Cain and Thorpe: "Synthetic Dyestuffs and Intermediate Products" (Substituents in Naphthalene Ring). The authors are indebted to Dr. Tesh for complete proof-read- ing and to other members of the Department of Chemistry of the University of Pittsburgh for criticism. The authors will at all times welcome suggestions and criticism. ALEXANDER LowY. BENJAMIN HARROW. IJournal of the American Chemical Society, 41, 1029 (1919). 74 ce in ti( fo in m yi m fi] ri fit fc d C ACETALDEHYDE Another polymer of formaldehyde may be obtained by treating the substance with sulfuric acid and evaporating the solution. The paraformaldehyde (also known as " paraform ") so obtained is a solid and is represented by the formula (CH20)., where x stands for a number not yet definitely fixed. The formaldehyde gas may again be obtained by simply heating the polymerized formaldehyde. Acetaldehyde, CH3 - CHO (also called ethanal), is manufactured by passing acetylene into dilute H2S04 in presence of mercury salts (catalyst). It is probable that what happens may be repre- sented thus: HH HH H H I + HOH I + HOH / C-C >C > H-C-C-O H -- CH3 CHO H OH H R Acetaldehyde may be polymerized, just like formaldehyde. If acetaldehyde is treated with sulfuric acid we get paraldehyde: 3CH3 CHO -+ (CH3.CHO)3 or CH- I C H I I\CH3 0 \C/0 CH3 H which, since it does not contain the carbonyl (>CO) group, no longer behaves like an aldehyde. If the temperature be lowered (say to 0O), instead of getting paraldehyde (a liquid), we get an isomeric compound, metaldehyde (a solid), with the same formula. Paraldehyde when heated with dilute acids is converted back to acetaldehyde. (Paraldehyde is used in medicine as a soporific.) Whereas PC15 reacts with aldehydes, replacing the 0 of the CHO group by two Cl atoms, chlorine gas displaces the hydrogen atoms in the alkyl part of the molecule; so that, if acetaldehyde be taken as a type, we may get the following: CHa-C// + 3C2 --, CC3 CHO + 3HCl \H Trichloro- acetaldehyde or chloral ALDEHYDES AND KETONES Chloral is prepared on a large scale from ethyl alcohol (see page 44). Chloral is an oily liquid with a penetrating smell. It reacts with water, forming chloral hydrate, /H CC13.-C OH or CC13 C- O H20 \OH H which is used as a soporific. In large doses, it acts as an anesthetic. Chloral also combines with alcohol to form a crystalline body /H CCl3 -C OH \OC2H5 Chloral alcoholate Bromal, CBr3. CHO, and iodal, CI3 -CHO are also known. By means of dilute alkali, or a zinc chloride solution, two molecules of acetaldehyde may be made to combine with one another to form aldol, a derivative of butyraldehyde. C -0 HC C/0 H CH3-C + HCH2-C -- CH3-C CH2 - CHO \HH OH 2-Hydroxy-4-butanal (or aldol) This is known as the aldol condensation, and, among other things, serves as a working hypothesis to explain the synthesis of fats in the plant kingdo,m and the conversion of sugars into fats in the animal body. Aldehydes are detected (a) by their reduction of an ammoniacal silver nitrate solution to silver (silver mirror); (b) by the " resin " formation obtained with NaOH; (c) by the formation of a reddish violet color with magenta, which has been decolorized with SO2 (the Schiff test); and (d) by reduction of an alkaline copper sul- fate solution (Fehling' test), giving the red cuprous oxide. CHO Glyoxal, I , is a dialdehyde. Its dimethyl derivative is CHO CH3 - C==O dimethyl glyoxal, I , and the dioxime of the latter is CHa - C-O UNSATURATED ALDEHYDES CH3-C=NOH dimethyl glyoxime, I , a substance used in the CH3-C-NOH gravimetric determination of nickel. Unsaturated Aldehydes.-Acrylaldehyde, CH2 CH-CHO, (commonly called acrolein, and sometimes called propenal), is prepared either (1) by the oxidation of allyl alcohol, or (2) by heat- ing glycerol with a dehydrating agent, as KHS04, or (3) by heating fats and oils to a somewhat high temperature. (1)CII, = CH - CH20H 0 CH,2=CH.CHO + HO20 (2)C H 2 OH CH2 I -2HOH 1 CHOH CHO (The odor of burning fat and the odor observed when candles are extinguished are mainly due to acrolein. Due to its toxic and lachrymatory properties, it was used as a " tear gas " during the late war.) The properties of acrolein depend, first, upon the fact that it has a double bond (and is, therefore, an unsaturated compound), and second, that it is an aldehyde; so that we get reactions such as these: CH2 CH2 11 0 H1 CH - CH CHO COOH Acrylic acid CH2 CH3 II H2 0 CH ----P CH2 CH20H CH20H Allyl alcohol Propyl alcohol ALDEHYDES AND KETONES Geranial or citral. CH3 /CH3 CH3 is found in oil of lemons and citrons. KETONES Acetone, CH3-CO-CH3 (also called propanone and dimethyl ketone) is prepared commercially by heating calcium acetate, and may also be isolated from the products obtained in the fermenta- tion of maize, etc. This liquid has a characteristic odor, a peppermint-like taste, and is miscible with water. b.p. 56.10. It is flammable. Acetone is used in the manufacture of chloroform, iodoform, sulfonal, smokeless powder, celluloid, etc. The chart facing p. 78 shows in detail the uses of acetone. Acetone is an excellent solvent for animal and vegetable oils and for fats, gums, resins, cellulose acetate, nitrocellulose, etc. Its chemical reactions have already been given (p. 71). (Acetone is present in the urine and in the breath of persons suffering from severe diabetes.) Full scan of this foldout is at the end of this text CHAPTER VIII ACIDS An organic acid contains the " carboxyl" group, -COOH -C ), and may be regarded as a hydrocarbon (O \OH/' in which one or more of the hydrogens is replaced by COOH groups; e.g., CH3H - CH3 - COOH. If the compound con- tains one COOH group, it is known as a monobasic acid; if two such groups, dibasic; if three, tribasic; etc. The basicity depends on the number of -COOH groups present in the molecule. We have analogous types in inorganic chemistry; e.g., HC1-H2SO4- H3P04, etc. Nomenclature.-Several acids have names that suggest their origin (formic from " formica," butyric from butter, valeric from " valeriana," palmitic from palm oil, etc.). The acids may also be named by changing the ending e of the hydrocarbons con- taining the same number of carbon atoms, to oic; so that CH4, methane becomes H COOH, methanoic acid C2H6, ethane becomes CH3 COOH, ethanoic acid C3Hs, propane becomes CH3 CH2 - COOH, propanoic acid C4H1o, butane becomes (a) CH3-CH2-CH2--COOH, butanoic acid (3) (2) /H (1) (b) CH3-C COOH, 2-methyl-1- \CH3 propanoic acid This type of nomenclature is seldom used. Or they may be named as derivatives of acetic acid, CH3 C OH; e.g., H C2H5-C H COOH, ethyl methyl acetic acid \CHa ACIDS or as the acids of the corresponding aldehydes: H -. CHO, formaldehyde CH3. CHO, acetaldehyde C2H5 CHO, propionaldehyde -H - COOH, -- CHa - COOH, - C2H5 COOH, Types of Acid Derivatives.-Acids in which some element or group has been substituted in the - COOH group are called " acid derivatives " (they will be taken up in detail in a later chapter): /0 \OM* * M= metal. R - C// 0 \OR , a salt; as an ester; as , an acyl halide, as CH3-C,/O \0O-Na Sodium acetate CHa3-C0 \0-C2H5 Ethyl acetate CH3-C1 c Cl Acetyl chloride //0 The R-C- group is known as the " acyl " group; CH3. group is the acetyl group. O \, R-C/ \O an acid anhydride, as 0 R -NC , an acid amide, as NH2 R C-N, An acid nitrile or an alkyl cyanide, as CH3-C// CH3-C/ Acetic anhydride CH3-C/ \NH2 Acetamide CH3 C-N Acetonitrile or methyl cyanide Types of Substituted Acids.-Acids in which the -COOH groups remain, but substitution has taken place in the residual formic acid acetic acid propionic acid, etc. '/0 C- MONOBASIC ACIDS groups (as CH3), are known as " substituted acids." be taken up in detail in later chapters.) Illustration with acetic acid: (They will CH3- COOH CH2-COOH, chloroacetic acid Cl CH2-COOH, hydroxyacetic acid OH CH2-COOH, cyanoacetic acid CN CH2-COOH, NH2 CH2-COOH, \COOH aminoacetic acid carboxvace(tic acid (known as malonic acid) CH2-COOH, sulfoacetic acid \SO:H (The -S03aH group is known as the sulfonic acid group or sulfo group.) The student should at this point thoroughly familiarize him- self with these type compounds, as frequent allusion will be made to them. MONOBASIC ACIDS (FATTY ACID SERIES'), R-COOH General Methods of Preparation.-. Oxidation of a primary alcohol, or of an aldehyde; e.g., 0 0 CH3-CH2OH -+ CH3. CHO -- CH3. COOH 2. Hydrolysis of esters (in presence of acids or alkalies); e.g., CH3. COOC2H5 + HOH CH3COOH + C2H5OH Ethyl acetate 'Named Fatty acids because many of them are contained in fats, or are formed from fats on hydrolysis. CONTENTS ALIPHATIC SERIES CHAPTER PAGE I. INTRODUCTION ...................................... 1 II. SATURATED HYDROCARBONS OR PARAFFINS AND PETROLEUM. 18 III. UNSATURATED HYDROCARBONS OR OLEFINS AND ACETYLENES. 30 IV. HALOGEN DERIVATIVES OF HYDROCARBONS ................ 40 V. ALCOHOLS............................................. 48 VI. ETHERS.......... .................... .......... ............. 64 VII. ALDEHYDES AND KETONES ............................... 67 VIII. ACIDS.................................... .................. .. 79 IX. SALTS AND ESTERS OF INORGANIC AND ORGANIC ACIDS.... 90 X. FATS AND OILS, WAXES AND LIPOIDS ................... 99 XI. ACID ANHYDRIDES, ACYL HALIDES AND ACID AMIDES ...... 107 XII. HALOGEN SUBSTITUTED ACIDS AND HYDROXY ACIDS....... 117 XIII. AMINES OR ORGANIC BASES ............................ 132 XIV. AMINO ACIDS AND PROTEINS ............................. 137 XV. NUCLEOPROTEINS, PURINES, URIC ACID AND PYRIMIDINES.... 149 XVI. CYANIDES, ISOCYANIDES AND OTHER NITROGEN COMPOUNDS. 154 XVII. CARBOHYDRATES AND RELATED COMPOUNDS ............... 160 XVIII. FOODSTUFFS AND THEIR CHANGES IN THE BODY........... 174 XIX. SULFUR, PHOSPHORUS, ARSENIC AND ORGANO-METALLIC COMPOUNDS............................. ............ 182 AROMATIC SERIES XX. INTRODUCTION TO CYCLIC COMPOUNDS ................... ......188 XXI. CONSTITUTION OF BENZENE AND THE AROMATIC HYDRO- CARBONS................................. ........... 191 XXII. HALOGEN DERIVATIVES, SULFONIC ACIDS AND NITRO COM- POUNDS OF THE AROMATIC HYDROCARBONS. ............. 210 XXIII. AROMATIC AMINES, DIAZO AND Azo COMPOUNDS .......... 222 XXIV. AROMATIC ALCOHOLS, PHENOLS AND ETHERS .............. 235 XXV. AROMATIC ALDEHYDES, KETONES AND QUINONES .......... 245 XXVI. AROMATIC ACIDS AND THEIR DERIVATIVES ................ 253 XXVII. ADDITIONAL AROMATIC COMPOUNDS CONTAINING MIXED G ROUPS.... ................. ....... ................ 261 XXVIII. NAPHTHALENE, ANTHRACENE AND THEIR DERIVATIVES ..... 278 ACIDS 3. Hydrolysis of acyl halides with water; e.g., CH3.COCl + HOH -+ CH3COOH + HC1 Acetyl chloride 4. Hydrolysis of alkyl cyanides or of acid amides; e.g., H20 O0 CH3 - C-N ---- CH3-C,/ NH2 Methyl cyanide Acetamide HO CH NHH CH3-C/ ONH2H2 H2S04 O > CH3-C + NH4HSO4 OH (A -CN group hydrolyzes to a -COOH group.) 5. Decomposition of salts of organic acids with mineral acids; e.g., CH3 COONa + H2S04 -- CH3 COOH + NaHS04 Sodium acetate General Properties. The lower members up to C9H19 COOH are liquids with strong odors, and the higher ones, waxy solids. They ionize to a slight extent (e.g., CH3COO-H+) but their salts ionize quite considerably. They are stable substances and difficult to oxidize. The acids form: (a) Salts with bases; e.g., CH3-CO00 H HO Na CH3 . COONa + H20 Sodium acetate (b) Esters with alcohols; e.g., H-COO H + H0 C2H5 -- HCOOC2H5 + H20 Ethyl formate (c) Acyl halides with PC15; e.g., C2H5COOH + PC15 -- C2H5COCl + POC13 + HCl Propionic acid Propionyl chloride (d) Halogen substitution products (where halogen sub- stitutes in the alkyl group); e.g., CH3COOH + Cl2 -- CH2. COOH + HCl C1 Chloroacetic acid NORMAL FATTY ACIDS NORMAL FATTY ACIDS * Name Formula Formic acid ................... H-COOH Acetic acid .................. CH3. COOH Propionic acid ............... C2Hs-COOH Butyric acid ................. C3H .COOH Valeric acid ................... C4H11-COOH Caproic acid .................. CsH11 COOH Heptoic acid ................. CGH,.COOH Caprylic acid ................ C7His -COOH Nonylic acid ................. CsH17-COOH Capric acid................... CH1119-COOH Undecylic acid ............... CoH21. COOH Laurie acid............... C1C23 COOH Palmitic acid ................ C15H31-COOH Margaric acid ................ C15H33-COOH Stearic acid................... C17H35-COOH Arachidic acid ............... C19H,39 COOH Melissic acid ................. C29H59-COOH * For source of these acids, see chapter on fats (p. 100). Formic Acid, H-COOH (also known as methanoic acid) is a colorless liquid, with an odor resembling sulfur dioxide. It is the strongest acid of this series. It occurs in bees, ants, nettles and pine needles. (The " stinging " by bees is due to penetration of formic acid under the skin.) Formic acid is manufactured by heating sodium hydroxide to 150'-170' with carbon monoxide under 6-7 atmospheres of pres- sure: CO + NaOH -- H-COONa Sodium formate In the laboratory, it is prepared by heating oxalic acid with glycerol. The reactions involved are somewhat complex, but the essential feature may be represented thus: COOH -- HCOOH + CO2 COO H ACIDS When formic acid is heated with sulfuric acid, we get carbon monoxide and water: HCOOH -- CO + H20 (CO cannot be regarded as the anhydride of HCOOH since CO mixed with water does not give formic acid.) Formic acid is a reducing agent. This may be explained on the theory that it contains an aldehyde (CHO) as well as an acid (COOH) group: H- C=O OH Formic acid is used in the manufacture of dyestuffs, in dyeing and finishing of textiles, in tanning, etc. Acetic Acid.-CH3.COOH (ethanoic acid), occurs in fruits and oils in the form of esters. The common form, known as vine- gar, is produced by the fermentation of fruit juices (such as the apple), which contain sugar. The sugar is first converted to alco- hol (due to the presence of the enzyme, zymase), giving us cider, and the latter is oxidized to acetic acid by oxidizing bacteria pres- ent in the juice. For large scale production, dilute (6-9 per cent) alcoholic liquor (product of fermentation) is allowed to trickle over beechwood shavings, which are impregnated with " Bacterium aceti," or mother of vinegar. Air is admitted on the side of the vats to oxidize the C2H50sO into CH3a. COOH. The tempera- ture is kept at about 350. After the conversion of the alcohol to acetic acid, the product is sold as vinegar. Vinegar contains from about 3-6 per cent of acetic acid, but also contains other acids (derived from fruit), esters, albuminous matter, etc. Stronger concentration of the acid is obtained from " pyroligneous acid," which contains acetic acid (4-10 per cent), this being separated from the other constituents of pyroligneous acid by conversion into calcium acetate, (CH3COO)2Ca and the subsequent liberation of the acid by the addition of sulfuric acid. Glacial acetic acid is practically 100 per cent acetic acid, and, as its name implies, resembles ice when frozen. Acetic acid is used as a solvent and to prepare acetates. It DIRECT INDUSTRIAL APPLICATIONS TEXTILE PAINTAND VARNI! INDUSTRY1 I INDUSTRY DYEING AFTER TREAT- TU AN C EN.WVOR5 Id IENT OF COTTO AN SULFUR COL& WSIE LEAD DDRE 5ALK CLOT ON COTTON EALIACIICOTTON I OFCRAIE TSET HIN TATES USED IPRINTING I PAINT IFOR CCU IAS MORDAT5 RIOE LACUI GARMENT CLEANING Full scan of this foldout is at the end of this text INDUSTRY TEUCO ADDln I SLV IIu ODIANTON Iii LAUNDRY MONUFACTUR . 'RDOCNO OLME I I FONFORNOL A D AIFENAE ING PHEOL H BLTHED AND IIOPEETI V II , R~5,I mPESJ RDAC [G UNSATURATED MONOBASIC ACIDS is also employed in the manufacture of dyes, drugs (like acetanilide, p. 225) and white lead. The chart facing p. 84 shows the exten- sive uses of acetic acid. Propionic Acid.-C2H5- COOH, is present in small amounts in pyroligneous acid. Butyric Acid.-CH3CH2CH2COOH, occurs in two forms: as the normal (the formula for which has just been given), and the CH3 iso, CH CH. COOH. The normal variety is present in rancid butter, muscle, sweat, cheese, feces, etc. It has a disagreeable odor. (Calcium butyrate is one of the few substances more soluble in cold than in hot water.) Isovaleric Acid, C CH. CH2. COOH, occurs in angelica and valerian roots. Palmitic Acid, C15H31 - COOH, and stearic acid, C17H35. COOH are widely distributed, accompanied by oleic acid, C17H33. COOH, in most animal and vegetable oils and fats, as the glyceryl esters. (See Chapter X.) From these esters the acids are obtained by hydrolysis; e.g., C3H5(OOC.C15H31)3+ 3HOH -+ 3C15H31 COOH + C3H5(OH)3 Palmitin (Superheated Palmitic acid Glycerol steam + H2SO4) The stearin candles of commerce consist of a mixture of palmitic with excess of stearic acid, and some paraffin added to prevent crystallization and brittleness. UNSATURATED MONOBASIC ACIDS Acrylic Acid, CH2=CH-COOH (also called propenoic acid) shows characteristic properties due to its double bond and to its carboxyl group. Crotonic Acid, CH3-CH=-CH. COOH, derives its name from croton oil. Oleic Acid, CH3 (CH2)7CH=CH(CH2)7COOH, (C17H33 -COOH) is present as the glyceryl ester in fats and oils (p. 99), and is usually found associated with palmitic and stearic acids. Oleic acid is a liquid and on a large scale it is separated from the solid ACIDS palmitic and stearic acids by squeezing it out under hydraulic pressure. Commercial oleic acid is known as " Red oil " and is used for the manufacture of soap, greases, etc. It is an unsat- urated acid, having its double bond between the ninth and tenth carbon atoms. With hydrogen, it is converted into the saturated stearic acid. Linoleic Acid, C17H31COOH, contains two double bonds. It is present in the form of a glyceryl ester in linseed oil and other drying oils. DIBASIC ACIDS, CnH2n(COOH)2 These compounds contain two carboxyl groups. (They are analogous to H2S04, which contains two replaceable hydrogens.) They are capable of forming two series of salts, viz., acid and nor- mal, and likewise two series of amides, esters, chlorides, etc. The general type reactions are analogous to those given for monobasic acids. Oxalic Acid, COOH, is present, in the form of salts (potassium, COOH calcium, etc.) in some plants (oxalis variety). Rhubarb is rich in it. The urine often contains small quantities of calcium oxalate. Preparation.-Sugars, cellulose and starch, when oxidized with nitric acid, yield oxalic acid. The commercial method is to heat sawdust with NaOH at 2400, which yields sodium oxalate. A still more recent method is to heat sodium formate (obtained from carbon monoxide and sodium hydroxide, p. 83) to 4000: H COONa COONa -> I + H2 H COONa COONa Another method of preparation will be referred to because it is based on a reaction already discussed. When cyanogen is hydrolyzed, we get oxalic acid: CN COOH + 4H20 ---> + 2NH3 CN COOH UNSATURATED MONOBASIC ACIDS When oxalic acid is heated with sulfuric acid, we get carbon monoxide, carbon dioxide and H20: COOH I CO2 + CO + H20 COOH (The student will remember the reaction as a laboratory method for the preparation of CO. The C02 is removed by pass- ing the mixture of gases through alkali.) Oxalic acid is a highly poisonous substance (perhaps by liber- ating CO in the system). It is used in analytical chemistry, in the manufacture of dyes, bleaching, metal polishes, tanning, etc. Oxalic acid is the strongest organic acid. /COOH Malonic Acid, CH2R , was first obtained by oxidizing malic acid (the acid present in apples, p. 125). Its synthesis is accomplished as follows: C12 KCN CH3" COOH ---- CH2 - COOH CH2 - COOH C1 CN Cyanoacetic acid Hydrolysis C COOH > CH2 COOH When heated, malonic acid is first converted into acetic acid by the loss of C02: COOH CH - CH3COOH + C02 and this proves malonic acid to be a dicarboxylic acid derivative of methane. Succinic Acid, CIH2. COOH, occurs in amber, fossil wood and CH2. COOH in the urine of animals. It is produced in processes involving ACIDS fermentation and may be obtained by distilling synthesis may be accomplished thus: CH2 Br2 CH2Br CH2 CH2Br CH2CN Hydrolysis CH2COOH I > I CH2CN CH2COOH Ethylene cyanide When the acid is heated, it loses a molecule of converted to its anhydride: CH2. COOH CH2 - COOH water and is CH2-C I \o + H20 CH2-Co Succinic anhydride UNSATURATED DIBASIC ACIDS Two compounds with the formula C2H2(COOH)2 are known, one being maleic acid and the other fumaric acid. Fumaric acid occurs in various fungi, iceland moss, etc. Maleic acid is not a natural product. The formulas ascribed to the two isomers are: H-C-COOH 11 H-C-COOH Maleic acid (cis-form) H-C-COOH HOOC--C--H Fumaric acid (trans-form) This type of isomerism is known as the "ethylene" or " geometric type." 1 When maleic acid is heated it produces an anhydride. H-C-COOH -C-COOH H--C--COOH H-C-C H 0+110 - -CII O + H,O H-C--C0 Fumaric acid does not yield an anhydride, which suggests that a compound represented by two -COOH groups in juxta- position has the maleic acid formula. 1 It is suggested that the instructor show this type of isomerism with the Kekuld models. amber. Its UNSATURATED DIBASIC ACIDS 89 (The system of nomenclature adopted to distinguish between the two isomers is to term the compound with similar groups on the same side as the cis-form, and the compound with similar groups on opposite sides on the molecule as the trans-form.) Maleic acid is prepared on a commercial scale by the catalytic (air) oxidation of benzene vapor: H-C COOH C6H6 + 90 -- 1 -+ 2C02 + H20 H-C. COOH Both fumaric and inaleic acids on reduction yield succinic acid: CH - COOH CH2 COOH 11 + H12-, I CH- COOH CH2. COOH viii CONTENTS CHAPTER PAGE XXIX. DYES AND STAINS ..................................... 288 XXX. TERPENES AND RELATED SUBSTANCES ..................... 302 XXXI. HETEROCYCLIC COMPOUNDS .......... .................... 309 XXXII. VEGETABLE ALKALOIDS ................................. 319 XXXIII. ARSENIC AND MERCURY COMPOUNDS OF THE AROMATIC SERIES. 322 XXXIV. A BRIEF OUTLINE FOR THE IDENTIFICATION OF ORGANIC COMPOUNDS............... ................. ......... 327 GENERAL IOPICS XXXV. PLANT AND ANIMAL PIGMENTS: CHLOROPHYLL, CAROTIN, XANTHOPHYLL, FLAVONES, ANTHOCYANINS, HEMOGLOBIN AND BILE PIGMENTS ................................ 335 XXXVI. ENZYMES, VITAMINS AND HORMONES. .................... 339 XXXVII. SYSTEMATIC NOMENCLATURE OF ORGANIC COMPOUNDS...... 344 APPENDIX GLOSSARY. ...................... .. ................ 359 BOILING AND MELTING POINTS OF A NUMBER OF ORGANIC COMPOUNDS. 362 GENERAL REFERENCE BOOKS. .................................. 365 INDEX.............................................. ........... 377 CHAPTER IX SALTS AND ESTERS OF INORGANIC AND ORGANIC ACIDS SALTS SALTS of organic acids are important for a number of reasons. In the first place, they are used in the preparation of various organic compounds (see below); then again a number of them are the source of certain elements which the body needs; and finally a group of them belong to the household substances which go under the common name of " soap." In inorganic chemistry, a salt may be looked upon as an acid in which the acid hydrogen is replaced by a metal; e.g., HCI NaCI H2S04 NaHSOi Na2SO.1 Acid Salt Acid Acid salt Neutral salt In a similar way, when the acid hydrogen of an organic acid is replaced by a metal, we get a salt: R- COOH R. COOM* Acid Salt For example: CH3COONa (sodium acetate), (H COO)2Cu (copper formate), C17H33 - COONa (sodium oleate), etc. The naming of these salts is analogous to the naming of inor- ganic salts: H2S04 -- Na2SO4, sodium sulfate CHaCOOH - CH3 - COOK, potassium acetate COOH COONa, S- I sodium oxalate COOH COONa CH2- COOH CH2COO I --> I >Cd, cadmium succinate CH2 - COOH CH2COO * M = metal. 90 GENERAL PROPERTIES OF SALTS General Methods of Preparation.-1. The action of an acid on a base; e.g., CH3 COOH + NaOH - H CH3- COONa + H20 2. The action of an acid on an oxide, or a carbonate; e.g., 2CH3 - COOH + CaC03 -> (CH3 - COO)2Ca + CO2 + H20 General Properties.-They are usually crystalline substances and often contain water of crystallization. Some, when heated with soda lime, yield hydrocarbons; e.g., C2H5 - COONa + NaO H -- C2HsH + Na2CO3 Sodium propionate Ethane others yield aldehydes; H CO ONa and still others, ketones; CH3 COO cCa > CH,3CO CH3 + CaCO0 CH3COO The free acid may be liberated from these salts by the addition of a stronger acid; e.g., CH3 COONa + H2S04 --> CH3COOH + NaHS04 The ammonium salts, when heated, are first converted to the acid amides and then to the cyanides (the reverse process of converting a cyanide into the acid being one of hydrolysis); e.g., - H20 - H20 CH3 COONH4 ----- C3 CONH2 ---- CH3 CN +H20 +H20 92 SALTS AND ESTERS OF INORGANIC AND ORGANIC ACIDS Very many salts are known. The names and composition of only a few of these will be given: H-COONa COO Sodium formate Cu COO Copper oxalate CH3 - COO COOLi \Mn I CH3. COO COOH Manganese acetate Lithium hydrogen (acid) oxalate COO CH2 o Pb CH3 - CH2. COONH4 \COO' Ammonium propionate Lead malonate CH3. CH2 CH2 - COOK C17H35COONa Potassium butyrate Sodium stearate CH3 -COO CH O - COO Pb 3H20 is "sugar of lead "; the " basic lead acetate," used to purify sugar and many biological substances, is OH Pb ; " verdigris," or " green pigment," is a com- \OOC CH3 bination of copper hydroxide and copper acetate, Cu(OH)2. (CH3COO)2Cu; " Paris green," the insecticide, is a combination of copper arsenite and copper acetate, (CH3COO)2Cu Cu3As206; iron, aluminum and chromium acetates are used as mordants in dyeing and calico printing. Soaps.-The sodium or potassium salts of some of the higher acids (obtained from fats and vegetable oils), such as palmitic, C15H31 -COOH; stearic, C17H35COOH; .and oleic, C17H33COOH, are known as soaps. Without going into the details of manufac- ture of these soaps, it may be pointed out that the principle involved is the conversion of the fat into soap and glycerol by boiling with alkali, and the separation of the soap from the glycerol by a process known as " salting out," which means that salt (NaCI) is added to the mixture, whereby the soap comes to the surface and is then ladled off. The reaction may be represented thus: ESTERS CH2- OOC - C15H31 Na OH CH20H CH -O00CC15H31 + NaOH -- CHOH + 3C15H31COONa Sodium palmitate (a soap) CH2- OOC C15H31 Na OH CH20H Glyceryl palmitate Glycerol or palmitin (a fat.) The solid soaps are sodium salts while the soft soaps are potassium salts. Soaps added to " hard " water (containing cal- cium or magnesium salts in solution) have their sodium atom replaced by either calcium or magnesium, thereby forming soaps insoluble in water: 2C17H35" COONa+Ca(HC03)2-1(C7H35 - COO)2Ca+2NaHC03 Sodium stearate Calcium stearate This explains the " curds" formed when soap is used in hard water. (" Lead plaster " is a lead soap made from lead oxide or lead acetate, which has been boiled with fat and water. Lead, man- ganese or cobalt soaps are used as " dryers " in paints, to hasten the process of drying. Calcium soaps are used for lubricating greases. Zinc stearate finds extensive use in toilet powders. The " medicated " soaps contain one or more of such substances as carbolic acid, salicylic acid, sulfur, cresol, resorcinol, etc. Per- fume and coloring materials are often added to soaps.) ESTERS An ester is either an inorganic or organic acid in which the acid hydrogen has been replaced by an R group (or a salt in which the metal is replaced by an R group): HC1, acid RC1, ester H2S04, acid RHSO04, acid ester or R2S04 ester HON02, acid RON02, ester HONO, acid RONO, ester CH3 - COOH, acid CH3 - COOR, ester COOH, COOR COOR C acid | ester or | acid ester COOH, COOR, COOH, 94 SALTS AND ESTERS OF INORGANIC AND ORGANIC ACIDS Esters are widely distributed in nature, and are respon- sible for the characteristic odors of many fruits, flavors and flowers. They have very agreeable odors and are used as flavoring materials and in perfumes. Since they are volatile, the esters are also called " ethereal salts." They ionize to a very slight extent and are usually insoluble in water. General Methods of Preparation.-1. By the interaction of an alcohol and an acid; e.g., C2H5 OH + HfI -+ C2HsI + H20 C2Hs5OH + H 0OC-CH3 - CH3-COOC2H5 + H20 Ethyl acetate C2HsOH + H HS04 -- C2H5HSO4 + H20 Ethyl hydrogen sulfate C25H OH + HI ONO - C2HsONO + H20 Ethyl nitrite 2. By the interaction of a salt of an acid with an organic halide; e.g., CH3COO Ag + I C3H7 -- CH3 COOC3H7 + AgI Propyl acetate 3. The action of an acyl halide on an alcoholate; e.g., C2H50 Na + Cl OC.CH3 --> CH3 - COOC2H5 + NaCl Acetyl chloride General Properties.-The esters are neutral substances, insol- uble in water. Though the salts ionize quite readily, the esters do not. Upon boiling with dilute acid or alkali, hydrolysis takes place, the process being known as saponification (a process em- ployed in making soap); e.g., CH3 - COOC2H5 + HOH - CH3COOH + C2H5OH Ammonia converts them to the corresponding amide; e.g., CH3 .CO OC3H7 + HINH2 -4 CH3 - CONH2 + C3H0H Acetamide Esters of Inorganic Acids.-(The alkyl halides discussed in Chap. IV (p. 43) are esters of hydriodic, hydrobromic and hydro- chloric acids. They will not be discussed again in this section.) Ethyl nitrite, C2H5. ONO, has an apple-like odor. Its alco- holic solution is the "sweet spirit of nitre." Isoamyl nitrite, ESTERS CsH11 ONO, is used in medicine as an antispasmodic and ano- dyne. Ethyl nitrate, C2H50N02, has a fruity odor. It is explosive. Dimethyl sulfate, (CH3)2S04, may be prepared thus: CH30H + HHS04 -+ CH3HSO4 + H20 2CH3HS04 heated -- (CH3)2S04 + H2SO4 It finds use as a methylating agent (to introduce methyl groups into compounds). Ethyl sulfuric acid, C2H5HSO4 (also called ethyl hydrogen sulfate), may be prepared by the action of cone. sulfuric acid on ethyl alcohol at 1000: C2H5OH + H2S04 -- C2H5HS04 + 1120 It may be recalled at this point that when ethyl hydrogen sulfate is heated to about 1700 we get ethylene (p. 42) and when treated with alcohol it yields ether (p. 65). Diethyl sulfate, (C2H5)2SO4, is used as an ethylating agent. It has a peppermint-like odor. Glyceryl trinitrate, commonly, but erroneously, called nitro- glycerine, is prepared by the action of nitric acid on glycerine (H2S04 is used as dehydrating agent): CH20H HON02 CH2- N02 I I CHOH + HON02 --> CH-ON02 + 3H1120 CH20H HON02 CH2-ONO2 It is used in medicine as a circulatory depressant and is the active constituent of dynamite (see p. 62). Glyceryl phosphate (ortho) is prepared in a similar manner: CH,2 OH HO0 CHOH -+ HO- P = 0 -- C3H'P4 + 3H20 Glyceryl orthophosphate CH, OH H 0 SThe C3H, group, if trivalent, is known as the glyceryl group; if C3H5 is monovalent, it is known as the allyl group. 96 SALTS AND ESTERS OF INORGANIC AND ORGANIC ACIDS (RCN may be regarded as an ester of HCN. This type of compound will be treated later-(p. 155.) Esters of Organic Acids.-When an inorganic acid and an alkali react, a salt is immediately formed; when, however, an organic acid and an alcohol (in some respects the analogue of the alkali) react, the ester is formed, but slowly: CH3COO H + HO C2H5 CH3COOC2H5 + H20 When equimolecular quantities are used, only 66 per cent of the ester is produced. An increase of temperature increases the velocity of the reaction, but not the yield of ester. The latter may be increased by the addition of a catalyst, or a dehydrating agent, such as H2S04 or HCI gas. Saponification to which we have alluded (p. 94) is hydrolysis, and esterificatiori is the reverse of this: Esterification. (strong acids) R-COOH + HOR' I R.COOR' + H20 Saponification (weak acids or bases) Many of these esters are known. They are used extensively in artificial fruit essences, flavors, perfumes, extracts, etc. Very many soft drinks on the market are artificially colored and fla- vored. Synthetic esters are used to flavor them and a number of coal-tar dyes to color them. Only a few can be mentioned here. Ethyl acetate, CH3. COOC2H5, is used as a solvent for nitro- cellulose, in the preparation of photographic films, and in resins and essences. Isoamyl acetate, CH. COOC5H, is found in pcar oil and is used as a solvent for gun-cotton and in the preparation of banana oil or " bronzing " liquid. Ethyl butyrate, C3H7'COOC2H5, is a constituent of pine- apples. Isoamyl isovalerate, C4H9. COOC5H11, is found in apples. Octyl acetate, CH3 - COOCsH17, occurs in oranges. Ethyl formate, H - COOC2H5, is a constituent of artificial rum. Amyl butyrate, C3H7. COOC5H,l has an apricot flavor. ESTERS MIyricyl palmitate, C15H31. COOC30H61, is present in beeswax. The esters of dibasic acids are also well known; e.g., COOCH3 COOH Methyl acid oxalate CH2COOC2H5 COOC2H5 Ethyl malonate (malonic ester) Uses of Malonic Ester.-Malonic ester can be used to synthe- size homologues of malonic and acetic acids. When malonic ester is treated with sodium or sodium alcoholate, the following reaction takes place: /COOC2H5 COOC2H5 + NaOC2H5 -- CH COOC2H5 |\COOC2H5 + C2H50H Sodium malonic ester If an alkyl halide is now added; e.g., COOC2H5 /COOC2H5 CH + C2H --+ C-H COOC2H5 , COOC2H5 (1) C2H5 Ethyl malonic ester a derivative of malonic ester is obtained. A second alkyl group (the same or a different one) may be introduced by repeating the above operation; e.g., C.OO C21H1 \COOC2H5 C2H C2H5 CH3 COOCH5 COOC2H5 C I Na + I CH3 --C C\ ICOOCC, H IC COOC2H5 (2) C2H11r, C2H5 Sodium ethyl malonie ester Ethyl nmethyl malonic ester On hydrolysis with sodium hydroxide and subsequent acidifi- cation the following acids are formed: CH3 /COOH (1) C/ -H I \COOH C2H5 Ethyl malonic acid S/COOH (2) -* C H I \COOH C2H acid Ethyl methyl malonic acid COOC2H5 COOC2H5 Ethyl oxalate 98 SALTS AND ESTERS OF INORGANIC AND ORGANIC ACIDS On heating, malonic acid and its derivatives lose carbon dioxide. COOH H CH3 COOH CH3 (1) C H - C-H (2) C-COOH --+ C C COOH \COOH \COOH C2H5 C2H5 C2H5 C2H5 Butyric acid Ethyl methyl acetic acid (Fats and vegetable oils are glyceryl esters. They will be taken up in detail in the next chapter.) READING REFERENCE ROGERs-Manual of Industrial Chemistry. (1921), pp. 723-738 (Soaps and Soap Powders). CHAPTER X FATS AND OILS, WAXES AND LIPOIDS FATS AND OILS THESE are glyceryl esters of fatty acids (usually of high molecu- lar weight). An example of one of these substances is glyceryl palmitate (tripalmitin). CH2-OOC - C15H31 CH -OO- CC15H31 CH2-OOC - C15H31 The glyceryl esters of stearic (C17H35COOH), palmitic and oleic (C17H33COOH) acids constitute the main bulk of the fats and oils in food and of body fat. If the three acid radicals in a fat or oil are the same, it is known as a simple glyceride, e.g., tripalmitin. A fat containing radicals of two or three different fatty acids is known as a mixed glyceride, e.g., CH2-OOC C17H35 CH -OOC.C15Hz1 CH2--OOC C3H7 Butyropalmitostearin There is no essential chemical difference between fats and vegetable oils. Stearin, C3H5(OOC.C17H35)3, and palmitin, C3H5(OOC-C15H31)3 are solids, while olein, C3H5(00C-C17H33)3 is a liquid. The consistency of a fat or oil depends on the amount of solid or liquid esters present. The fats are solid at the ordinary temperatures, whereas the oils are liquid. 99 NOTE FOR STUDENT REMEMBER that the laws in chemistry hold for organic as well as for inorganic chemistry. Correlate as many of the new facts with facts with which you are already familiar from your previous studies. Classification in organic chemistry has been carried to an exceptional degree. One type reaction often gives the key to hundreds of individual reactions. Emphasize, therefore, type formulas and type reactions and make constant use of paper and pencil to practice the writing of formulas and equations. To broaden your outlook, consult as frequently as possible the reading references given at the end of chapters. 100 FATS AND OILS, WAXES AND LIPOIDS IMPORTANT FATS AND OILS Fat or Oil Contains the Glyceryl Ester of Source of Fat or Oil Almond oil Oleic, palmitic, linoleic acids, etc. Bitter or sweet almonds Butterfat Butyric, caproic, capric, palmitic, Cow's milk stearic, oleic acids, etc. Cacao butter Palmitic, oleic, stearic, myristic Seeds of cocoa nibs acids, etc. Castor oil Ricinolcic, stearic, oleic acids, etc. Seeds of castor beans Cocoanut oil Caproic, caprylic, capric, lauric Seeds of "cocos nucifers," acids, etc. kernel of nuts Codliver oil Oleic, myristic, palmitic, stearic Livers of cod fish acids and cholesterin, etc. Cottonseed oil Oleic, stearic, palmitic, linoleic acids, Seeds of the cotton-plant etc. Hemp oil Isolinolenic, oleic acids, etc. Seeds of hemp Human fat Stearic, palmitic, oleic, butyric, Human beings caproic acids, etc. Lard Stearic, palmitic, oleic, linoleic acids, Body fat of swine etc. Linseed oil Linoleic, linolenic, oleic, palmitic, s,Ceeds of flax myristic acids, etc. Maize oil Arachidic, stearic, palmitic, oleic Seed germs of corn oil acids, etc. Menhaden oil Palmitic, myristic, oleic, stearic, and Bodies of menhaden fish other unsaturated acids, etc. Mustard oil Erucic, arachidic, stearic, oleic acids, Seeds of mustard etc. Neatsfoot oil Palmitic, stearic, oleic acids, etc. Hoofs of cattle Olive oil Linoleic, oleic, arachidic acids, etc. Fruit of olive tree FATS AND OILS IMPORTANT FATS AND OILS-Continued Fat or Oil Contains the Glyceryl Ester of Source of Fat or Oil Palm oil Palmitic, lauric, oleic acids, etc. Palm seed Peanut oil Arachidic, linoleic, hypogoeic, pal- Peanuts mitic acids, etc. Poppy oil Linoleic, isolinolenic, palmitic, stear- Poppy seeds ic acids, etc. Rape oil Erucic, arachidic, stearic acids, etc. Rape seeds Sperm oil Oleic, palmitic acids, waxes, etc. Head and blubber of sperm whale Tallow Stearic, palmitic, oleic acids, etc. Fat of ox or sheep Whale oil Linoleic, isolinolenic acids, etc. Blubber of whales Oleomargarine consists mainly of refined lard, " oleo oil " (the soft part of beef fat) and cottonseed oil, often mixed with a small amount of butter and churned with milk or cream. Hydrogenation of Oils.-Liquid fatty oils can be converted to fatty bodies of almost any desired degree of consistency by means of hydrogenation. The unsaturated liquid oils unite directly with hydrogen in presence of catalysts (nickel being used on com- mercial scale) to form saturated bodies. C3H5(OOC-C17H33)3 + 3H2 -- C3H5(OOC-C17H35)3 Olein (liquid) Stearin (solid) Stearin has greater commercial value than olein. The " hardened fats " now find extensive use in the preparation of lard substitutes, in the manufacture of soap, etc. " Hardened " cottonseed oil, peanut oil and other edible oils have largely replaced lard com- pounds. " Crisco," " vegetol," are examples of " hardened " (or hydrogenated) vegetable oils. " Intarvin " (Glyceryl margarate (C16H33 - COO)3C3H5), has recently been introduced by Kahn in the treatment of diabetes. In this disease, it has been found that the naturally-occurring fats and oils, containing an even number of carbon atoms, give rise to 101 102 FATS AND OILS, WAXES AND LIPOIDS " acetone bodies " (P-hydroxybutyric acid, acetoacetic acid and acetone) which poison the system, whereas "intarvin " which is an odd-carbon fat, does not. Crude fats and oils range from yellow to red in color. The refined products are generally yellow to colorless. Sometimes vegetable oils are green, due to the presence of chlorophyll (the green coloring matter of plants). Fats and oils are insoluble in water, but readily soluble in ether, benzene, chloroform, etc. The rancidity of a fat (as in butter-fat) is mainly due to hydrolysis (bacterial decomposition, or otherwise) yielding the free fatty acids. Butter in this way produces butyric acid, which has a disagreeable odor. Properties.-Fats can be hydrolyzed or saponified. When the glyceryl esters of stearic, palmitic or oleic acids are saponified with NaOH or KOH, soaps are formed: CH2-OOC--C15H31 CH2OH CH -OOC-C15H31 + 3NaOH - CHOH + 3C15H31-COONa Sodium palmitate CH2-OOC--C15H31 CH20H (a soap) This is the principle employed in the manufacture of soap. (The reaction also explains the hydrolysis of fats in the small intestine by the enzyme (lipase) which is formed in the pancreas.) A number of methods used for identifying fats are: 1. Saponification value: the number of milligrams of KOH needed to saponify 1 gram of fat or oil. 2. The iodine number: the percentage of iodine absorbed by the sample. (The amount of " absorption," -or extent of " addition " will depend upon the amount of unsaturated glycerides present- such as in olein, for example.) 3. Specific gravity. 4. Melting point. 5. Index of refraction. 6. Viscosity and other physical constants. (As has been stated, the fats in the body are first hydrolyzed into fatty acids and glycerol. A little soap is also formed, due to the alkalinity of the medium. The fatty acids and glycerol are absorbed as such through the lining of the small intestine, where they are re-synthesized again into fat, most of which passes into WAXES the lymphatic system, and finally finds its way into the blood stream. Some of the fat is oxidized in the cells to CO2 and water, see the steps in this oxidation, p. 178, but much of it is often deposited in the adipose tissue, and acts as a reserve fuel.) The fats and oils, when strongly heated, either alone, or with a dehydrating agent like KHS04, develop a penetrating odor, due to the formation of acrolein. This acrolein is really derived from the glycerol part of the molecule: CH2OH -2H20 CH2 CH H CH CHHOH CHO Glycerol Acrolein or acrylaldehyde WAXES Waxes, like fats, are esters, but instead of containing the trihydroxy alcohol, glycerol, they contain high molecular weight monatomic alcohols, such as cetyl alcohol, C16H330H, carnaubyl alcohol, C24H490H, myricyl alcohol, C30H610H, etc. Among vegetable waxes, we have " carnauba wax," and among animal waxes, we have wool wax (or "lanolin "), beeswax, sper- maceti, Chinese insect wax, etc. Waxes (like fats) are soluble in ether, benzene, chloroform, car- bon tetrachloride, etc. Since they do not contain glyceryl radical, they do not yield acrolein when heated. The waxes do not become rancid like fats and are less easily hydrolyzed. Carnauba wax is derived from a species of palm; it is used in varnish, for candle making and for adulterating beeswax. Lanolin, obtained from wool grease, is used in pharmacy as a basis for salves, ointments and emulsions. Beeswax is derived from the honey- comb of bees and is used in candle making, in pharmacy, etc. Sper- maceti, found in the head of the sperm whale, finds uses in candle making, in pharmacy and in confectionery. Chinese wax, secreted by an insect, is also used in candle making, in medicine and as a furniture polish, etc. 103 FATS AND OILS, WAXES AND LIPOIDS LIPOIDS These are a group of substances, soluble in ether and the usual fat solvents, which are found in abundance in animal tissues, par- ticularly in the brain. We know little at present about their physiological significance. They may be classified as follows: 1. Containing nitrogen and phosphorus (phosphatids); e.g., lecithin and cephalin (N : P as I : 1), and sphingomyelin (here N : P as 2 :1). 2. Containing nitrogen: e.g., phrenosin and cerasin (the so- called " cerebrins " or " cerebrosides "). 3. Nitrogen and phosphorus are absent; e.g., cholesterol. Lecithin is a combination of glycerol, fatty acid, phosphoric acid and choline, and its structure may be represented as: CH2-OOC. R CH -OOC R' CH2-O HO-P=O /C2H4-O N=(CH3)3 \OH (R and R' represent groups present in acids. As in fats, R .and R' may be the same or different.) C2H40H -CH3 Choline, N CH3 CH3 OH or trimethyl-P-hydroxyethyl ammonium hydroxide, is closely related to muscarine-the aldehyde hydrate of choline- CH3\ OH CHa-N/ OH CH3/ \CH2-CH/ OH 104 LIPOIDS which is the poisonous constituent of the deadly toad-stool, and to betaine-the acid anhydride- 0 CH3\ CH3-N CO CH3/ \CH2 a non-toxic plant product. In a crude form, lecithin may be obtained by extracting egg yolk with ether and precipitating with acetone. Cephalin is similar to lecithin in that it contains glycerol, fatty acids and phosphoric acid, but in the place of the base choline, it contains aminoethyl alcohol, CH2 CH20H. Its con- NH2 stitution may be represented as CH2.00C-R CHI OOC- R' //o CH20-P-0O-CH2 - CH2 NH2 OH Unlike lecithin, cephalin is insoluble in alcohol. (Cephalin is sometimes written " kephalin.") Sphingomyelin is a complex combination of phosphoric acid, choline, a base, sphingosine, C17H32(OH)NH2, and an acid, ligno- eerie acid, C25H47 - CO(H. Phrenosin is a combination of cerebronic acid (the hydroxy acid of lignoceric), galactose and sphingosine. Cerasin, like phrenosin, yields when hydrolyzed, galactose and sphingosine, but in the place of cerebronic acid gives lignoceric acid. Cholesterol, C26H430H or C27H450H, is an unsaturated sec- ondary alcohol and a member of the terpene series, though its exact structure is not yet known. It is widely distributed in animal tissues, particularly in egg yolk and nervous tissue. (An isomer, phytosterol, is found in the vegetable kingdom.) " Lan- olin," the fatty matter obtained from sheep's wool, is an ester of cholesterol. This alcohol is also present in bile and in blood. The determination of the amount of cholesterol in the blood is 106 FATS AND OILS, WAXES AND LIPOIDS often of chemical significance, since in gall stones, pregnancy, nephritis, diabetes, etc., the quantity may be in excess of the normal value. READING REFERENCES MACLEAN-Lecithin and Allied Substances. LEVENE-Structure and Significance of the Phosphatides (Lecithin, etc.). Physiological Reviews, 1, 327 (1921). LEATHEs-The Fats. ROGERS-Manual of Industrial Chemistry. (1921), pp. 653-689 (Oils, Fats and Waxes); pp. 701-710 (Hydrogenation of Oils). MITCHELL-Edible Oils and Fats. PHILLIP-Romance of Modern Chemistry. (1910), chap. 21 (Fats and Oils). CHAPTER XI ACID ANHYDRIDES, ACYL HALIDES AND ACID AMIDES THE type formula for an acid anhydride is R-C0 R-C 0 The type formula for an acyl halide is R-C 0 -\X The type formula for an acid amide is O R - C N H 2 ACID ANHYDRIDES Acid anhydrides are similar in many respects to inorganic acid anhydrides. Sulfur trioxide, for example, is the acid anhydride of sulfuric acid, for SO3 + H20 -- H2S04. Simi- larly, acetic (acid) anhydride is the anhydride of acetic acid, for CH3'C OH OH CH8-C -H2 0 CH3.C O ±H20 2CH3COOH CH3-*C Acetic anhydride TO (An anhydride may be looked upon as an acyl oxide.) 107 108 ACID ANHYDRIDES, ACYL HALIDES AND ACID AMIDES General Methods of Preparation.-1. By heating an acyl halide and the salt of an acid, e.g., CH3CO Cl + Na OOCCH3 -+ CH3 C + NaCI (fused) 0 CH3 C \\o 2. By the action of a dehydrating agent (such as P205) on the acid. Acetic anhydride may in this way be prepared from glacial acetic acid. However, the yield is poor. Acetic anhydride is the most important member of the series and the general properties of these anhydrides can be illustrated by summarizing the properties of acetic anhydride. (Formic anhydride is not'known.) It has already been mentioned that acetic anhydride reacts with water to form acetic acid. With alcohol, a mixture of acid and ester is formed: CH3CO O0 + HI OC2H, -- CH3COOH + CH3 - COOC2H5 CH3CO/ Ethyl acetate With propionic acid, a mixed anhydride is obtained: CaH7. CO (CH3CO)20 + C3HCOOH --- /0 + CH3COOH CH3CO / With ammonia, the corresponding amide is formed: CH3CO CHCO O + H NH2 - CH3CONH2 + CH3COOH CH3CO/ Acetamide Chlorine and bromine yield substituted anhydrides; e.g., CH2Cl -CO o /0 CH3-CO / (Chloroacetic anhydride) Acetic anhydride is a liquid with a pungent, suffocating odor. It finds extensive use as a means of introducing the CH3CO (acetyl) group into compounds. ACYL HALIDES Succinic anhydride may be obtained by heating succinic acid: CH2COOH CH2CO I O + H20 CH2COOH CH2CO Similarly maleic anhydride may be obtained from maleic acid: CH-COOH CH.CO I -* II O + H20 CH-COOH CH-CO The properties of these compounds are analogous to acetic anhydride ACYL HALIDES Acyl Halides, R-C X, may be regarded as acids in which the OH of the COOH group is replaced by a halogen: R-COOH - R -COCI (The acyl chloride compounds are common, but few of the corresponding iodide and bromide compounds are known, and they are used only infrequently.) Nomenclature.-The group R-C is known as the " acyl" group. 0 The group CH3-CO is known as the " acetyl " group. 0 The group C2H5-C1 is known as the " propionyl " group. Therefore, in naming the acyl halide, we need merely change the ic (last two letters) of the acid to yl. (Formyl chloride is not known. When the attempt is made to prepare it, it breaks down into CO and HCl: H-COCl -- CO + HCI) Acetyl chloride finds extensive use in organic syntheses and its preparation and properties will, therefore, be considered. 109 110 ACID ANHYDRIDES, ACYL HALIDES AND ACID AMIDES Preparation.- 1. By the action of phosphorus pentachloride, phosphorus trichloride, or phosphorus oxychloride on acetic acid, or sodium acetate: CH3COOH + PC15 -- CH3COC1 + POC13 + HCl CH3COONa + PC15 -- CH3COC1 + POC13 + NaC1 3CH3COOH + PC13 > 3CH3COC1 + P(OH)3 2. The commercial method of obtaining the chloride is to heat sodium acetate and to pass sulfur dioxide and chlorine over it. The sulfur dioxide and chlorine combine to form sulfuryl chloride: SO2 + C12 - S02C12 which then reacts with the sodium acetate: 2CH3COONa + S02C12 - 2CH3COCl + Na2SO4 Properties.-Acetyl chloride is used extensively to introduce the CH3--C (acetyl) group into organic compounds. It is a very reactive substance. The moisture of the atmosphere very readily converts it to acetic acid: CH3COI Cl + H OH - CH3COOH + HCI Acetyl chloride reacts with sodium acetate to form acetic anhydride: CH3COC1 + NalOOCCH3 -- (CH3CO)20 + NaC1 and with ethyl alcohol to form an ester: CH3CO Cl + H OC2H15 - CH3.-COOC2H115 + HC Ethyl acetate and with ammonia to form an amide: CH3COI Cl + H INH2 -> CH3CONH2 + HCI Acetamide /01H If the OH grouos in carbonic acid, C=O are replaced by Cl, 1OH we get C=O (chloroformyl chloride), which is commonly known \Cl ACID AMIDES as phosgene. This substance is a colorless, suffocating gas. Owing to its poisonous character, the comparative ease with which it can be liquefied and prepared (by passing chlorine and carbon monoxide over charcoal), phosgene was used very extensively in the late war. It was loaded in shells and bombs and exploded when the shell struck ground. Phosgene is also used in the manilfacture of dyes. Water decomposes phosgene as follows: Cl HJOH OH C O -+ CO + 2HCl \IC1 HOH \OH -CO2 + H20 + 2HC1 (The poisonous effects of phosgene are said to be due to the liberation of a high concentration of HCl gas.) Ethyl alcohol forms an ester: Cl H fOC2H5 OC2H5 CO + -> CO + 2HC1 C1 H OC2H5 OC2H5 Ethyl carbonate Ammonia transforms phosgene into urea (or carbamide): C1 H INH2. NH2 CO + -, CO C1 HJNH2 NH2 Other acyl halides are: COCl COCI I CH2 COC1 COCl Oxalyl chloride Malonyl chloride, etc. AcID AMIDES Acid Amides, R-C , may be looked upon as acids in NH2 which the OH group is replaced by NH2. Or, they may be regarded as derived from ammonia, NH3, in which one of the hydrogen atoms is replaced by the RCO (acyl) group. The 112 ACID ANHYDRIDES, ACYL HALIDES AND ACID AM IDES -NH2 group when attached to an acyl group is known as the " amido " group. If the -NH2 group is attached to an alkyl group, it is known as the " amino " group. The nomenclature is based on the names of the corresponding acids (amides of acids); e.g., H - CONH2, formamide CH 3-CONH2, acetamide C2H - CONH2, propionamide C3H7 CONH2, butyramide, etc. (With the exception of formamide, which is a liquid, all the others are solids.) Preparation and Propert ss.-(Acetamide will be taken as a type.) 1. The action of ammonia on acetyl chloride: CH3CO ICl + HI NH2 -- CH3CONH2 + HCI 2. The partial hydrolysis of methyl cyanide: CH3CN + H20 --> CH3CONH2 3. The action of ammonia on acetic anhydride: CH3CO /O + HINH2 -> CH3COOH + CH3CONH2 CH3CO/ 4. The dehydration of ammonium acetate (by heating): CH3CO H2 - CH3CONH2 + H20 (The group NH4, or HNH3 is basic; so is the compound RNH2. The compound RCONH2 is practically neutral, a result due to the acid properties of RCO and to the basic properties of NH2.) Acetamide is transformed into ammonium acetate when boiled with acids or bases (compare with reaction 4 above): CH3CONH2 + H20 --- CH3COONH4 and when dehydrated forms methyl cyanide (compare with reaction 2 above); CH3CONH2 - H20 --> CH3CN Hofmann's reaction.-This is a method by which the CO group can be eliminated from an amide, so that R-CONH2 ACID AMIDES becomes RNH2 (amine). When acetamide is treated with bromine in an alkaline solution the following reactions take place: CH3CONH2 + Br2 -* CH3CONHBr + HBr Acetbromoamide CH3CONHBr + 3KOH -- CH3NH2 + KBr + K2C03 + H20 Methylamine Urea (carbamide or aminoformamide), CO NH2 may be \NH2 considered as the diamino derivative of carbonic acid, CO/ H \OH This is a substance of great biological importance, since it is the chief end product resulting from the changes that proteins undergo in the body. (The amount of urea in the urine is directly proportional to the amount of protein present in the food which is eaten.) Preparation.-1. By heating ammonium cyanate: NH4-CNO ± CO(NH2)2 This method was discovered by W6hler in 1828. The student will recall that Wihler's preparation is one of the earliest recorded instances of the laboratory preparation of an " organic " substance (p. 1). 2. By the action of ammonia on phosgene: Cl H NH2 CO< + -- CO(NH2)2 + 2HCl Cl H NH2 3. By the action of ammonia on ethyl carbonate: 0C2H5 H INH2 CO/ + - CO(NH2)2 + 2C2H50H OC2H5 H NH2 Properties.-Urea is easily hydrolyzed, yielding carbon dioxide and ammonia. These same products are also obtained when the enzyme urease (found in the soya bean, etc.) is allowed to act on 113 114 ACID ANHYDRIDES, ACYL HALIDES AND ACID AMIDES urea. (Incidentally, by far the best method for the determination of urea is based on its reaction with urease.) Nitrous acid liber- ates nitrogen, etc.: CO(NH2)2 + 2HONO --> CO2 + 2N2 + 3H20 So does sodium hypobromite: CO(NH2)2 + 3NaOBr -- CO2 + N2 + 3NaBr + 2H20 (This method was for a long time used to determine urea. The nitrogen evolved was measured, and from it the amount of urea in the shmple was calculated. The determination at best is only approximate for the errors involved are high. The method has been entirely replaced by the urease method.) Urea combines very readily with nitric and oxalic acids to form urea nitrate, CO(NH2)2 HN03, urea oxalate, [CO(NH2)212' (COOH)2, respectively. These salts crystallize very readily and are often used for identifying urea. When urea is heated, two molecules combine to form a sub- stance known as biuret: /NH2 /C co/Y y co \NH2 \NH2 Biuret When a drop of copper sulfate and a few cc.'s of fairly concentrated alkali are added to biuret, a violet color is formed. This is known as the " biuret reaction." All proteins give the biuret reaction-a reason for assuming that the protein molecule has, among other things, a " biuret " configuration. NH2 Guanidine, HN=CNH2 , is related to urea. Creatine, \NH2 HNCNH2 \N--CH2 COOH, or methylguanidine acetic acid CH3 ACID AMIDES is a constituent of muscle; and its anhydride, creatinine, NH HN=--C CO, is a normal constituent of urine. N-CH2 CH3 /NH2 (A number of derivatives of urea, such as urethane, C-0 , \OC2H5 /NH-C /C2H5 or ethyl carbamate, barbital, C=O C , or diethyl- \NH-C/ C2H5 NH- 41 C2H5 malonyl urea, and luminal, C=O C>" , or phenyl \NH-C \O C6H5 ethyl malonyl urea, are used extensively as hypnotics.) CONH2 Oxamide, I , is formed as follows: CONH2 COOH PC15 CO C1 H]NH2 CONH2 I ) + -- COOH COC1 H NH2 CONH2 /CONH2 CH11CONH 2 is malonamide \CONH2 CH2 CONH2 I is succinamide CH2 CONH2 When succinamide is heated, we get succinimid, the >NH group being known as the imido group: CH2CO NH2 CH2-CO I- -oNH + NH3 CH2CONH H CHz--CO' 116 ACID ANHYDRIDES, ACYL HALIDES AND ACID AMIDES The mercuric salt, CH2-CO OC-CH2 S >N. Hg. N I CH2-CO OC-CH2 is used in the treatment of syphilis. READING REFERENCES SLossoN-Chats on Science. (1924), No. 12 (Perfumes from Poison Gas). WERNER-The Chemistry of Urea. CHAPTER XII HALOGEN SUBSTITUTED ACIDS AND HYDROXY ACIDS THESE are acids in which one or more of the hydrogen atoms in the group, which is attached to the COOH group, is replaced by X, OH, CN, NH2, etc. For example, CH2 - COOH, acetic acid, H gives rise to CH2 COOH CH2 - COOH CH2 - COOH CH2 -CO0IT I I I C1 OH NH2 CN Chloroacetic acid Hydroxyacetic acid Aminoacetic acid Cyanoacetic acid HALOGEN SUBSTITUTED ACIDS Preparation.-The action of chlorine on acetic acid: CH3COOH + C12 -- CH2ClCOOH + HCl CH3COOH + 2C12 - CHC12COOH + 2HCl Dichloroacetic acid CH3COOH + 3C12 * CC13COOH + 3HCl Trichloroacetic acid (The number of hydrogen atoms replaced by chlorine atoms depends upon the amount of chlorine used, the temperature and the time of the reaction. These reactions are carried out in the presence of sunlight and " carriers "-catalysts-such as iodine or sulfur.) Analogous compounds may be formed by substituting bromine for chlorine, but here the reaction proceeds only under pressure and at higher temperatures. Iodine does not react. (In order to make such a substance as iodoacetic acid, we allow potassium iodide to react with chloroacetic acid: CH2C1 COOH + KI -- CH2I. COOH + KC1.) 118 HALOGEN SUBSTITUTED ACIDS AND HYDROXY ACIDS Better yields are obtained in the following way: 3CH3 COOH + PBr3 --+ 3CH3 COBr + P(OH)3 CH3 COBr + Br2 -- CH2Br -COBr + HBr Bromoacetyl bromide CH2Br -COBr + H20 -- CH2Br -COOH + HBr Direct halogenation always replaces the hydrogen attached to the a-carbon. The nomenclature may be gathered from this graphic illustration:-CH2-CH2-CH2-CH2-COOH. 3 y 3 a The p-halogenated acids may be obtained in the following way: CH2 CH2COOH CH2--CHCOOH + HBr -> I Acrylic acid Br ,-Bromopropionic acid (The halogen enters the position as far removed from the COOH group as possible.) a- and p-halogenated acids may be prepared thus: CH2-CHCOOH CH2=CHCOOH + Br2 -- I Br Br a, P-Dibromopropionic acid Halogenated acids may also be prepared from hydroxy-acids: CH2 . CH2COOH CH2-CH2COCl I + PC15 - OH Cl i-Hydroxypropionic acid i-Chloropropionyl chloride CH2-CH2COOH + H20 -- I Cl P-Chloropropionic acid Properties.-Some of the properties (such as the formation of salts, esters, etc.) are due to the presence of a carboxyl group and some to the radical attached to the carboxyl group. For example, the greater the number of halogens attached to the carboxyl group, the stronger the acidity. Trichloroacetic acid, HALOGEN SUBSTITUTED ACIDS CC13COOH, is a strong acid. The a-halogen acids in the presence of hot alkali yield the corresponding hydroxy-acids: CH2COOH CH2COOH I + HOH -- I + HC1 Cl OH The 0-halogen acids yield unsaturated acids when heated with water or alcoholic KOH; e.g., CH3- CH-CH. COOH I -- CH3 -CH=CH -COO I C HI Butenoic acid (Crotonic acid) (In certain cases-where, for example, sodium carbonate is used-CO2 is also evolved, so that butenoic acid is converted to the corresponding unsaturated hydrocarbon, CH3 - CH=CH2.) The y-halogen acids form with water inner anhydrides or lactones; e.g., H20 CH2 - CH2 - CH2 - COOH CH2 CH2 - CH2 COO H Cl OH -y-Chlorobutyric acid SC2- CH2 2- CH2-C=O 0 Butyrolactone With ammonia, the halogen-substituted acids form amino- acids: CH2Cl. COOK+HNH2 --+ CH2NH2 - COOK --> CH2NH2 - COOH With potassium cyanide, we get the cyano-acids; e.g., CH2CI-COOK + KCN -- CH2CN-COOK -> CH2CN-COOH Very many of these halogen-substituted products are known. Chloroacetic acid, CHI2CI1COOH, is used in the manufacture of synthetic indigo. The vapors attack the eyes, and they also act corrosively on the skin. Trichloroacetic acid, CC13. COOH, also acts corrosively on the skin and is used to remove warts and other growths. It has recently come into use as a protein pre- cipitant. When boiled with water we get chloroform: CC13 COOH CHCl3 + CO2 119 AN INTRODUCTION TO ORGANIC CHEMISTRY CHAPTER I INTRODUCTION LONG ago man conceived the idea that between the living and the lifeless there is a sharp dividing line. A careful study of the colors of the spectrum, or a consideration of evolutionary problems, might have made him reconsider this view. It would have been more logical to assume that we probably cannot tell just where the " lifeless " ends and the "living" begins. And that, indeed, is the modern point of view. But even as late as a century ago, chemists still had faith in the classification of chemical compounds into " organic " or " inorganic," the " organic " being distinguished from the " inor- ganic " on the supposition that the former had some kind of " vital " or " life force," which made it seem quite impossible that a chemist could ever hope to reproduce an " organic " substance in the laboratory. (Formerly substances of mineral origin were classed as " inorganic "; those of animal or vegetable origin were classed as " organic.") These notions of " organic " and " inorganic " were rudely shaken by the work of Whler, a distinguished German chemist, who in 1828, succeeded in preparing urea in his laboratory by heating ammonium cyanate (p. 113). Now if any one compound can be called " organic," such a distinction certainly belongs to urea, for it is the chief end product of the decomposition of pro- teins in the body and is the principal nitrogenous constituent of the urine. 120 HALOGEN SUBSTITUTED ACIDS AND HYDROXY ACIDS HYDROXY ACIDS /OH CO , carbonic acid or hydroxyformic acid \OH CH2 COOH I , hydroxyacetic acid or glycolic acid. OH /H CH3-CCOOH, a-hydroxypropionic acid or lactic acid. \OH CH2-COOH 1 , hydroxysuccinic acid or malic acid. CHOH- COOH CHOH- COOH , dihydroxysuccinic acid or tartaric acid. CHOH- COOH CH2 - COOH HO-C - COOH , citric acid. CH2- COOH General Methods of Preparation.-1. Hydrolysis of halogen acids; e.g., H20 H CH3-C,COOH CH3-C COOH Cl OH c-Ch!loropropionic acid a-Hydroxypropionic acid or lactic acid 2. The hydrolysis of the addition product formed when hydrogen cyanide reacts with an aldehyde; e.g., O HCN /OH Hydrolysis /OH CH3-C< -- CH3--C--COOH \H H \H Acetaldehyde hydrogen cyanide Lactic acid 3. The oxidation of a primary alcohol containing a hydroxyl group; e.g., H Oxid. CH2-C/CH20H - CH2-CH-COOH OH OH OH OH Glycerol a- P-Dihydroxypropionic acid or glyceric acid HYDROXY ACIDS 4. Action of nitrous acid on amino-acids; e.g., /H H CH3-C-COOH + HONO -- CH3-CCOOH + N2 + H20 \NH2 \OH a-Aminopropionic acid Properties.-As might be expected, these compounds show the properties both of hydroxy and carboxylic substances. The chloro-acids are formed with PC15; e.g., CH2 COOH + PC15 -- CH2COOH + POCl3 + HCI OH Cl When the hydroxy-acids are heated, two molecules unite with the elimination of two molecules of water: CH2 COO H,-' CH2- CO I I I 0H~ OH 0 0 HIOOC-CH CO - CHR Glycolic acid Glycolide In a similar manner lactic acid is converted to lactide. When 0-hydroxy acids are heated, we get unsaturated acids; e.g., CH2. CH. COOH I I --> CH2=CH- COOH OH HI Acrylic acid or propenoic acid p-Hydroxypropionic acid When y-hydroxyacids are heated an inner anhydride (lactone) is formed; e.g., CH2-CH2--CH2 COO CH2-CH2-CH 2C-=0 Butyrolactone This is also true of 8-hydroxyacids. Hydroxyacetic acid, CH20H COOH (also known as glycolic acid) occurs in unripe grapes. H a-Hydroxypropionic acid, CH3-C-C00H (better known \OH 121 122 HALOGEN SUBSTITUTED ACIDS AND HYDROXY ACIDS as lactic acid), is known in three forms, the dextro and levo optically active modifications, and the racemic, or inactive form (which can, however, be resolved into the two optically active forms). Optical Activity.-Three forms of lactic acid are known. These three varieties have the same chemical and physical proper- ties but behave quite differently towards polarized light. One turns the plane of polarized light to the right (and is, therefore, known as dextro, or d-lactic acid); the other turns it to the left (levo, or i-variety); and the third is inactive (dl). This last is made up of equal parts of the dextro and levo forms.' Le Bel and van't Hoff, quite independently of one another, discovered that all optically active substances have at least one carbon in the molecule attached to four different atoms or groups. For example, in lactic acid: H CH3-C*-COOH OH we have a carbon atom marked * which is attached to H, OH, CH3 and COOH. Such a carbon atom is known as an asymmetric car- bon atom. Structurally, the d-form of lactic acid is related to the i-form as an object is to its mirror image: CHa CH3 HO-C--H H-C-OH COOH COOH d-form -form 1 By polarized light we mean light in which all the vibrations lie in one plane. An ordinary ray of light vibrates in every direction. Polarized light may be obtained by passing ordinary light through a Nicol prism or tourmaline plate-as illustrated in the instrument known as the "polarimeter." An optically active substance has the power of rotating this plane of polarized light, the extent depending, among other things, upon the nature of the substance. For further details, consult a practical physical chemistry; for example, Firth-Practical Physical Chemistry. HYDROXY ACIDS Usually, when a compound containing an asymmetric carbon atom is synthesized, we get equal parts of the dextro and levo varieties. Such a mixture is designated as dl-, or i (inactive), and is known as " racemic." This inactive mixture can, as a rule, be resolved into the active constituents in a number of different ways. One of these depends upon the property which certain organisms possess of destroying one component more rapidly than another. For example, bacteria destroy the I-lactic acid and penicillium the d-lactic acid. The souring of milk is due to the formation of lactic acid (the inactive variety), and this is brought about by the action of cer- tain bacteria (which are also present in the air) on the milk sugar or lactose present in the milk. The acid so formed precipitates the principal protein (caseinogen) in milk, giving rise to what is known as " curdling." The synthetic lactic acid of commerce is prepared from acetaldehyde, as follows: 0 OH Hydrolysis /OH CHa3-C +HCN-CH3--3CN CH3- C-OOH H H H Lactic acid is made commercially by fermentation of sugar. It is a colorless, viscous liquid and is used in medicine, dyeing and calico printing. The antimony, zinc and iron lactates are used as mordants. Silver lactate is a powerful antiseptic. Dextro-lactic acid, or d-lactic acid (also called sarcolactic acid and paralactic acid) is found in muscle tissue, meat extract, blood and urine. Inactive muscle is alkaline and after activity it becomes acid, a change which has been ascribed to the formation of lactic acid. When the d-acid is heated it loses its optical activity and is converted to the inactive or dl- variety. Levolactic acid, or I-lactic acid, is obtained when sugar is fer- mented with bacillus acidi levolactici. The d- and 1- lactic acids and the dl- or i- variety show the same physical and chemical properties; they differ only as regards optical activity. (The intermediate changes that proteins, fats and particularly sugars undergo in the body in their ultimate breakdown to carbon dioxide, water and simple nitrogenous bodies, are associated with the formation, it is believed, of lactic acid, among other sub- stances. The evidence is accumulating to show that lactic acid 123 LOUIS PASTEUR (1822-1895) CHEMIST, FOUNDER OF THE MODERN SCIENCE OF BACTERIOLOGY AND ONE OF THE GREATEST SCIENTISTS OF ALL TIMES. ONE OF HIS EARLIEST RE- SEARCHES DEALT WITH THE CRYSTALLINE FORMS OF TARTARIC ACID AND ITS SALTS (P. 126), AND THIS LED DIRECTLY TO LE BEL AND VAN'T HOFF'S CONCEP- TION OF STEREOISOMERISM. 124 HYDROXY ACIDS is an important intermediate product in the decomposition within the body of the common foodstuffs.) (An isomer of lactic acid is P-hydroxypropionic acid, or hydracrylic acid, CH2-CH2 COOH, in which the hydroxyl OH group is in the #-position.) Hydroxysuccinic acid, CH2 COOH (commonly known as CH(OH) -COOH malic acid) is present in unripe apples, cherries, grapes, etc. It may be prepared from bromosuccinic acid by the action of silver hydroxide: CH2. COOH CH2 - COOH I + AgOH - + AgBr CH- COOH CH COOH Br OH Malic acid is optically active and has the general properties of hydroxy acids. Dihydroxysuccinic acid, CH(OH) COOH (commonly known CH(OH) - COOH as tartaric acid), contains two hydroxyl groups and is a dibasic acid. It can be prepared from dibromosuccinic acid by the action of silver hydroxide: CHBr - COOH CH(OH) COOH I + 2AgOH - I + 2AgBr CHBr COOH CH(OH) - COOH The reduction of tartaric acid (with hydrogen iodide) first yields malic acid and then succinic acid. Interesting, also, is the fact that maleic acid, or fumaric acid, representing the unsaturated dibasic acids, may be converted to tartaric acid by oxidation with potassium permanganate: CH - COOH CH(OH)- COOH II + H20 - O - CH - COOH CH(OH) . COOH Maleic acid or fumaric acid 125 126 HALOGEN SUBSTITUTED ACIDS AND HYDROXY ACIDS The following four forms of tartaric acid are known: COOH COOH COOH H-C*-OH HO-C*--H Equal mixture H-C*--OH I I of I HO-C*-H I-C*-OH (A) and (B) H-C*-OH I I is I COOH COOH dl-Tartaric acid COOH (inactive) -Tartaric acid &-Tartaric acid Meso-Tartaric acid (A) (B) (C) (D) Thus we have two forms of tartaric acid which are optically active [(A) and (B)]; and two which are optically inactive [(C) and (D)]. (A) is the mirror image of (B), while in (D) the upper part of the graphic formula is a mirror image of the lower part. (C) can be resolved into the d- and 1- forms, while (D) can- not. (C) is said to be optically inactive by external compensation, while (D) is optically inactive by internal compensation. d-Tartaric acid is the one found in grapes in the form of potassium acid tartrate. 1-Tartaric acid may be obtained from the inactive form by " splitting " or resolution into the active isomers. Racemic (inactive) or dl-acid, is found in grapes and is formed when the d- acid is boiled with NaOH solution. It may be resolved into the d- and 1- forms. A fourth variety, meso-tartaric acid (first prepared by Pasteur by heating the cinchonine salt of d-tartaric acid) is also inactive, but, unlike the racemic acid, cannot be resolved into the d- and 1- forms. (The history of tartaric acid is intimately associated with the development of our ideas of optical activity and of the asymmetric carbon atom; and with these ideas the names of Pasteur, van't Hoff and Le Bel will forever be linked. It was Pasteur who first showed that the racemic acid was really a mixture of two types of crystals, one the image of the other, and that when mechanically separated and dissolved in water, the one type turned polarized light to the right and the other turned it to the left, suggesting at once that the racemic acid was really a mixture of the d- and 1- forms. The later researches of van't Hoff and Le Bel connected optical activity with the presence of one or more asymmetric car- HYDROXY ACIDS bon atoms within the molecule. There are two asymmetric carbon atoms in the molecule of tartaric acid; these have already been referred to.) Salts of Tartaric Acid. - Potassium acid tartrate, CH(OH) COOK (also known as cream of tartar) is a constituent CH(OH) COOH of baking powders, and is used in dyeing. Sodium potassium tartrate, CH(OH)-COOK -4H2O (com- CH(OH) - COONa monly known as Rochelle salt), is a constituent of Fehling's solution and is also used as a purgative (in " Seidlitz " powders). Potassium antimonyl tartrate, CH(OH) -COOK (also known CH(OH) - COO(SbO) as tartar emetic), is used in medicine as an emetic, and also in dyeing. Citric acid, CH2 - COOH, is a monohydroxy tribasic acid, and HO-C--COOH . H20 CH2 - COOH is found in lemons (from the juice of which it is commonly pre- pared), berries, limes and other acidulous fruits. It is also pre- pared on large scale by the fermentation of glucose or sucrose, by certain mould fungi as citromycetes pfefferianus. It is used in lemonade and other beverages, and in calico printing. Magnesium citrate (C6H507)2Mg3 is used as a laxative, and ferric ammonium citrate, in blue-print paper manufacture and in calico printing. Sodium citrate is used extensively for the pre- vention of blood coagulation. Acetoacetic acid, CH3. CO- CH2 - COOH, or acetyl acetic acid, and its ethyl ester, acetoacetic ester, CH3 CO CH2 - COOC2H5 are here considered because the ester may be looked upon as a derivative of a p-hydroxy unsaturated acid: CH3 - CO - CH2 - COOC2H5 or CH3 . C=-CH - COOC2H5 OH 128 HALOGEN SUBSTITUTED ACIDS AND HYDROXY ACIDS Acetoacetic acid is one of the " acetone bodies " present in the urine of persons suffering from diabetes, and it is commonly known as " diacetic acid." It is an unstable acid and decomposes into acetone: CHa3CO CH2 COO H -- CH3.CO-CH3 + C02 which explains. the presence of acetone in the urine and breath of diabetics. Acetoacetic ester, CH3 CO CH2. COOC2H5 (or, more cor- rectly, ethyl acetoacetate) is a compound of considerable impor- tance in synthetic organic chemistry. Claisen's explanation of its synthesis, which follows, is the one generally accepted to-day: 1. 2C2H50H + 2Na -- 2C2H5ONa + H2 0 /ONa 2. CH3-C/ + NaOC2H5 -- CH-C--OCoH5 \0C2H5 \OC2H5 ONa 3. CHa3-C- OC2H5 H CH-COOC25 OC2H5 + H C-0C2H5 /ONa -+ CH3-C CHCOOC2H5 + 2C2E50H Sodium acetoacetic ester /ONa 4. CH3-C CHCOOC2H5 + CH3COOH /OH -- CH3-C/=CHCOOC2H5 + CH3COONa Acetoacetic ester Tautomeric forms: OH /O CH3-C/CHCOOC2H5 = CH3-C-CH2COOC2H5 Enolic Ketonic Acetoacetic ester is prepared by the action of sodium on ethyl acetate. A small amount of alcohol is needed for reaction (1); additional quantities of alcohol are formed as shown in (3). /O \H The enolic form -C CH-), first produced [see (4)], rear- ranges to the more stable keto form (-C OCH2-). An equi- librium mixture of the enolic and ketonic forms contains 7 per cent and 93 per cent respectively. HYDROXY ACIDS (The type of isomerism wherein, under certain conditions, a compound passes from one structural form into another, is known as tautomerism.) Acetoacetic ester is a colorless liquid with a fruity odor. Uses of Acetoacetic Ester.-Depending upon the reagents used, as well as the concentration of solutions, the following two types of decomposition take place: (a) Ketonic hydrolysis: CH3.CO.CH2. CO 0OC2H5 H OH Dil. aqueous or ale. acids or alkalies >CH3 CO CH3 + CO2 + C2H5OH (b) Acid hydrolysis: CH3'CO CH2'CO O'C2H5 HO H HO H Cone. ale. KOH or Cone. aqueous KOH > CH3COOH + CH3COOH + C2H5OH One or both hydrogens in the -CO - CH2- part of the aceto- acetic ester may be replaced by various groups, giving rise to sub- stituted acetoacetic ester derivatives. (A somewhat analogous case may be found in malonic ester, p. 97.) If one mole of sodium ethylate reacts with one mole of acetoacetic ester, the compound /ONa CH3-C CHCOOC2H5 is produced. This reacts with an alkyl halide, for example, as follows: /ONa /0 CH3-C=CHCOOC2H5+ IC2H5-CH3- C-CHCOOC2H5 I C2H5 -+ CH3-C-CHCOOC2H5 (1) C2H5 Ethylacetoacetic ester INTRODUCTION This epoch-making work of Wbhler's was not, as is generally supposed, at once accepted unconditionally. Sometimes the sci- entist does not take to scientific changes any more quickly than does the average citizen to social or political changes. But in time other examples of the production of " organic " substances in the chemist's laboratory were recorded, and the old idea became less and less important. Chemists prepared or synthe- sized acetic acid, fats, alcohol, oxalic acid, mustard oil, oil of bitter almonds, sugars, camphor, uric acid, indigo, adrenaline, protein- like substances and thousands of others, more or less complex- all, however, typically " organic " substances. And we are far from having reached the limit. It is conceivable that in the not distant future some of the food we use will be made in the chem- ist's laboratory. As an illustration of possibilities, within the past year, Kahn has prepared a synthetic fat, which he calls " intarvin," which is of value in diabetes (p. 101). Many are of the opinion that a judicious combination of the work of the physical chemist and the organic chemist will result, eventually, in solving the riddle of life itself. We still retain the words " organic " and " inorganic," though we no longer think of them in the time-honored sense. What we call " organic " chemistry may more aptly be called the chemistry of the carbon compounds, for that is just what " organic " chem- istry deals with. But in reality we do not draw the line too sharply. Such compounds as carbon dioxide, carbon monoxide, carbon disulfide, hydrogen cyanide and the carbonates are usually included in texts on inorganic chemistry, though, of course, they are carbon compounds, and according to the definition should be included under " organic " chemistry. The fundamental laws of chemistry, which the student has taken up in his inorganic chemistry course, apply to organic chem- istry with equal or perhaps greater force. If, then, the dividing line between " organic " and " inorganic " chemistry is not a sharp one, why the necessity for having these two subdivisions? We shall enumerate a number of reasons. 1. The number of compounds of carbon known to-day exceed 225,000, and the number of compounds which do not contain car- bon are only about 26,000. 2. In general, organic and inorganic compounds show marked 130 HALOGEN SUBSTITUTED ACIDS AND HYDROXY ACIDS (1) still contains a replaceable hydrogen atom CeCH- S o\C2H5 and by means of a series of analogous reactions another alkyl group may be introduced, giving, for example: 0 CH3 CH3-C-C-COOC2H5 (2) C2H, Ethylmethylacetoacetic ester On acid hydrolysis, (1) decomposes thus: CH3CO HO and (2): CH3CO HO CH-COO C2H5 H H C2H5 OH -- CH3COOH+C2Hs5 CH2 -COOH+C2H5OH H /CH3 C--COO C2H5 H C2H5 OH CH3 -+ CH3COOH + CH-COOH + C2H5OH C2H5 which means that we are able to build up (synthesize) mono- R basic acids of the types R-CH2COOH and CHCOOH. On ketonic hydrolysis, (1) decomposes thus CH3COCH- CO OC2H5 I - CH3 -CO -CH2 C2H5 + C02+C2HOH C2H5 H OH and (2): /CH3 CH3CO-C CO OC2H5 \C2H5 H OH /CH3 -- CH3CO'C H + 02 + C2 2H5OH \C2H READING REFERENCES 131 which means that we are able to synthesize higher ketones of the /R types R-CO-CH2 and R CO CH \R \R' ,Acetoacetic ester is also used in the manufacture of anti- pyrine-p. 311-and a number of dyes.) READING REFERENCES TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), Chap. 12 (Architecture of Molecules). JONES-New Era in Chemistry. (1913), Chap. 4 (Origin of Stereochem- istry). VALLERY-RADOT-The Life of Pasteur. STEWART-Chemistry and Its Borderland. (1914), Chap. 7 (Chemistry in Space). FINDLAY-Chemistry in the Service of Man. (1916), Chap. 11 (Molecular Structure). STEWART-Stereochemistry. HARROW-Eminent Chemists of Our Time. (1920), pp. 79-110 (van't Hoff). CHAPTER XIII AMINES OR ORGANIC BASES THESE compounds are derivatives of ammonia: /H /R /R / R N- NH N R N-R Ammonia Primary Secondary Tertiary amine amine amine /C2H5 /CH3 /CH. N-H N C2H5 C2H5 H H \CH3 Ethylamine Ethyl methyl- Dimethyl amine ethylamine R (In R NH2 the -NH2 is an amino group, in NH the R/ =NH is an imino group). We have similar relationships in NH40H, where one or more hydrogens in the NH4 group may be replaced by R groups. H CH3 C2115 H CH3 Hs N-H N--H N-C2H H \ zH OH OH OH Ammonium hydroxide Dimethylammonium hydroxide Tetraethylamminonium hydroxide Methods of Preparation of Primary Amines.--1. Theoreti- cally the simplest method should involve the reaction between ammonia and an alkyl halide: C2H5 I + HINH2 -> C2HsNH2 + HI but due to the basicity of C2H.5 NH2, an addition compound (C2H5NH3I, ethylammonium iodide) is first formed, which may PROPERTIES OF PRIMARY AMINES be decomposed by means of alkali just as an ammonium salt may be decomposed by means of alkali: C,H, N H =C2H5NH2 H20 + NaI I H + N LOH (This method is little used because of complicated secondary reactions which take place (p. 134)). 2. The action of bromine and a strong base on an amide, e.g., H CH3. CONH2- + Br2 + NaOH -- CH3-CO--N\Br Acetamide Acetbromoamide CH3CO. -NHBr + 3NaOH -* CH3NH2 + Na2CO3 + NaBr +H20 Methylamine In brief, CH3. CONH2 - CH3 NH2 (This is known as the Hofmann reaction.) Notice that the conversion of acetamide to methylamine involves the loss of a carbon atom. The Hofmann reaction is often used in the conversion of one member of a series to another containing one less carbon atom. (See indigo, p. 316.) 3. The reduction of alkyl cyanides; e.g., CH3CN + 2H2 -> CH3.CH2-NH2 Methyl cyanide Ethylamine Properties of Primary Amines.-These compounds are more basic than ammonia and are readily soluble in water. They have a strong, fish-like odor, and their vapors are flammable. They combine with acids, giving such compounds as methyl- ammonium bromide, CH3NH2 .HBr; methylammonium nitrate, CH3NH2-HN03, and methylammonium sulfate (CH3NH2)2. H2S04. The amines are acted upon by nitrous acid, yielding the corresponding hydroxy compounds: CH .-NH2 + HONO -- CH30H + N2 + H20 (The Van Slyke method for determining the rate of hydrolysis of a protein is based on this reaction. See under amino acids, p. 140.) 133 AMINES OR ORGANIC BASES Chloroform and alcoholic potassium hydroxide react with primary amines with the formation of isocyanides (isonitriles). ~;cl~C1~ C+ -H Cl 2KOH CHN H SC2H-N= - C2H-N= Methyl isocyanide (This is the carbylamine reaction and is used to distinguish primary from secondary and tertiary amines. The isocyanides have characteristic and highly disagreeable odors.) Methylamine is a common constituent of many putrefactive mixtures. Secondary and tertiary amines may be obtained by the fol- lowing series of reactions: CH3NH2 + ICH3 (CH3)2NH-HI + NaOH (CH3)2NH + ICH3 (CH3)3N-HI + NaOH H -CH3- CH3 I Dimethylammonium iodide (CH3)2NH + NaI + H20 Dimethylamine (a secondary amine) -- (CH3)3N HI Trimethylammonium iodide - (CH3)3N + NaI + H20 Trimethylamine (a tertiary amine) (Trimethylamine can combine with methyl iodide to form tetramethylammonium iodide (CH3)4. N.I. Since the reactions given above proceed more or less simultaneously, it becomes somewhat difficult to separate the different amines.) (For another method see p. 228.) The physical properties of the secondary and tertiary amines are similar to those of the primary amines. Trimethylamine is produced by the destructive distillation of the residue obtained in the sugar beet industry. They, and the primary compound, are found in herring brine and in the products obtained from the distillation of nitrogenous substances. The Action of Nitrous Acid on Primary, Secondary and Tertiary Amines.-It has already been stated that the action 134 SECONDARY AND TERTIARY AMINES of nitrous acid on a primary amine forms the corresponding hydroxy compound: e.g., C2H5 NH2 + HONO --> C2H5OH + N2 + H20 With secondary amines, nitrous acid forms nitroso compounds e.g., (C2H)2NIH + HO INO -- (C2H5)2N-NO + H20 Diethyl nitrosoamine (The nitroso-compounds are usually yellow-colored, volatile liquids of aromatic odor.) Tertiary compounds do not react with nitrous acid (though oxidation of an indefinite type may take place). Nitrous acid is, therefore, used to distinguish the amines. (The " carbylamine reaction" given above, p. 134, is specific for primary amines.) " Quaternary bases " are compounds derived from ammonium hydroxide; e.g., NH40H -+ N(CH3)4.OH Tetramethylammonium hydroxide (Choline, neurine and muscarine, compounds of physiological importance-See Chapter X-may be regarded as derivatives of quaternary bases.) Tetramethylammonium hydroxide may be prepared thus: N(CH3)41I + Ag OH -* N(CH3)40H + AgI It is a colorless, hygroscopic solid, the solution of which is strongly basic, resembling potassium hydroxide. When heated, it decomposes into trimethylamine: N(CH3)40H -- N(CH3)3 + CH30H which is really a very good method for the preparation of tertiary amines. Compounds containing two amino groups are known as diamines: Ethylenediamine may be made from ethylene bromide: CH2Br HNH2 CH2. NH2 I + -- + 2HBr CH2Br HNH2 CH2.NH2 135 AMINES OR ORGANIC BASES /CH2 N112 Trimethylene diamine has the formula CH2 N12 CH2 NH2 CH2 CH2- NH2 Tetramethylene diamine, I or putrescine, and CH2- CH2- NH2 pentamethylenediamine, (CH2)5(NH2)2, or cadaverine, are putre- factive products of the corresponding amino acids, ornithine and lysine (p. 142), and are found among the putrefactive products in the intestine. It is the belief that the putrefactive products in the intestine are formed by the action of bacteria on various amino acids, which are converted into the corre- sponding amines by loss of C02; e.g., CH2- NH2 CH2 NH2 (CH2)3 - (CH2)3 + C02 CH.NH2 CH2- NH2 I Cadaverine COOH a, -Diaminocaproic acid or Lysine (The chemical properties of the diamines are similar to the monoamines, except that as we have to consider two primary NH2 groups instead of one NH2 group.) (For a group of compounds related to the amines and of great physiological importance, such as choline, neurine, lecithin, betaine and muscarine, see Chapter X, p. 104.) 136 CHAPTER XIV AMINO ACIDS AND PROTEINS AMINO ACIDS AN amino acid is a compound in which a hydrogen in the group attached to the COOH is replaced by an NH2 group; e.g., CH2 COOH CH2 -COOH H NH2 Acetic acid Aminoacetic acid or glycocoll or glycine (The nomenclature is analogous to that used in the halogen and hydroxy substituted acids, so that CH2 CH2 COOH NH2 is p-Aminopropionic acid; and CH3" CH2 -CH COOH NH2 is a-Aminobutyric acid.) The a-amino acids are of great importance physiologically, since these are the main products obtained when proteins are hydrolyzed. Methods of Preparation.-1. The action of ammonia on halogen acids; e.g., CH2 COOH + HNH2 -- CH2 COOH + HC1 Cl NH2 Chloroacetic acid 2. The action of hydrogen cyanide on aldehydes and ketones, 137 AMINO ACIDS AND PROTEINS and the subsequent reaction with ammonia and ultimate hydroly- sis; e.g., //H0 /01 CH3 C< + HCN -- CH3C N Acetaldehyde cyanohydrin 0H HNH2 /NH2 CH3 - C CN + CH3 C-CN + H20 \H \H CH NH2 / NH2 C3 - C-CN + 2H20 - CH3 - C COOH + NH3 \H \H 3. The hydrolysis of proteins (either by enzymes, acids or alkalies) yields a succession of products (metaproteins, pro- teoses, peptones, polypeptides), the final products being amino acids. (In the digestive tract, the enzymes pepsin, trypsin and erepsin hydrolyze the various proteins of the food into different amino acids.) Properties.-Since the amino acids contain NH2 and COOH groups, they may act as bases or acids; e.g., CH2-COOH + HCl -- CH2-COOH NH2 NH2 -HC Glycine Glycine hydrochloride CH2COO0H + NaOH --> CH2.COONa NH2 NH2 (They are, in reality, amphoteric substances, like aluminium hydroxide or zinc hydroxide. Glycine, for example, is a feeble electrolyte and is partially dissociated thus: H2N. CH2COOH T- H2N-CH2COO + H (A) HO-H3N-CH2-COOH = HO + H3N-CH2-COOH (B) At some particular hydrogen ion concentration, the dissocia- tion represented by (A) will be equal to the dissociation repre- sented by (B). This is the " isoelectric point," and at this point the solution is electrically neutral. The significance of the " isoelectric point " and its bearing on the behavior of such substances as proteins, is only now beginning to be appreciated.) 138 EMIL FISCHER (1852-1919) ONE OF THE FOREMOST ORGANIC CHEMISTS OF THE NINETEENTH CENTURY, DID MUCH TO ELUCIDATE THE CHEMISTRY OF CARBOHYDRATES (P. 163), PURINES (P. 149) AND PROTEINS (P. 143). 139 INTRODUCTION differences in solubility, the former being usually soluble in ether, alcohol, chloroform, benzene, etc., while the latter are not; whereas many of the inorganic compounds are soluble in water and the organic ones are not. 3. The atoms of carbon have the unique property of combining with one another to form chain-like structures-a property not frequently shown by inorganic compounds: for example, HHH I I I H-C-C-C--H HHH 4. Organic compounds are, as a rule, less stable than inor- ganic; they are much more easily susceptible to chemical and physical changes. (Organic compounds are decomposed at rela- tively low temperatures.) 5. " Type " reactions are quite frequent in organic chemistry. For example, there are hundreds of organic compounds which react with nitric acid to form " nitro " compounds (p. 219), hundreds of which react with reducing agents to yield " amino " compounds, etc. 6. There is often a marked difference in the velocity of reac- tion. The change of one organic compound to another is usually a relatively slow process, whereas the transforma.tion of inorganic substances is often practically instantaneous. 7. Reactions in organic chemistry are, as a rule, mostly non- ionic, the solutions being non-conductors of electricity; whereas, reactions in inorganic chemistry are largely ionic. This explains, for example, why, when solutions of sodium chloride and silver nitrate are mixed, an immediate precipitate of silver chloride is obtained, whereas, we get no precipitate upon mixing solutions of pure carbon tetrachloride (CC14) and silver nitrate. 8. Reactions in organic chemistry often tend to become quite complex, and there are possibilities of many " side " or " second- ary " reactions (p. 215). 9. The complexity in structure exhibited by some organic compounds is quite unknown among inorganic compounds (p. 293). 10. Organic compounds often show a property called " isomer- ism " which we shall discuss later in some detail (p. 21), but AMINO ACIDS AND PROTEINS When dissolved in alcohol and saturated with hydrogen chloride (dehydrating agent), the amino acids form esters; e.g., CH2 COOH + C2H5OH -- CH2 COOC2H5 + H20 NH2 NH2 (Emil Fischer has used this " ester " method to separate the amino acids obtained by the hydrolysis of proteins.) Nitrous acid converts amino acids into the corresponding hydroxy compounds with the liberation of nitrogen; e.g., CH2 COOH + HONO -- CH2 COOH I+ N2 + H20 NH2 OH (This is the principle of the Van Slyke method for the deter- mination of amino acids in blood and tissues, and for following the rate of protein hydrolysis.) Aldehydes react with amino acids to form methylene deriva- tives; e.g., R.CH-COOH > R-CH-COOH H\ + H20 NJH2 +0 =C--H N=CH2 (This reaction converts an approximately neutral substance-- because of the presence of the NH2 and COOH groups-into an acid substance, by the substitution of the NH2 group. Sirensen has used this principle for determining amino acids in blood, urine and tissues, and for estimating the extent of protein hydrolysis. The greater the hydrolysis, the more free NH2 and COOH groups are formed and hence, when the NH2 group is removed by formaldehyde, the greater the acidity of the hydrolytic products.) Since an amino acid contains a basic and an acidic group, internal neutralization is possible, with the resulting formation of " inner "' salts: /o /COOH / 0 CH2 -* CH2 0 \NH2 NH3 140 AMINO ACIDS When an a-amino acid is heated, two of its molecules combine to form an anhydride: CH2. NHIH HO OC CH2-NH-CO C jOH HI HN CH2 CO-NH-CH2 Glycine anhydride p-Amino acids, when heated, lose ammonia and yield unsat- urated acids: CH2-CH-COOH -- CH2=CH-COOH I I Acrylic acid JNH2 HI f-Aminopropionic acid y-Amino acids give "lactams ": CH2CH2-CH2aCO O -* CH2 CH2 CH2-CO NHIH H HN y-Aminobutyric acid Butyrolactam (These reactions are analogous to those given under hydroxy acids, p. 121.) Amino acids obtained from the hydrolysis of proteins. Glycocoll, CH2 - COOH, also called glycine, is aminoacetic acid. NH2 Alanine, CH3 CH COOH, is a-aminopropionic acid. NH2 CH3 Valine, H CH - CH - COOH, is a-aminoisovaleric acid. CH3/ I NH2 CH3 Leucine, >CH CH2. -CH COOH, is a-aminoisocaproic CH3 NH2 acid. Phenyl alanine, CH2 - CH COOH, is 0-phenyl-a-aminopro- I I COHsNH2 pionic acid. AMINO ACIDS AND PROTEINS Tyrosine, CH2 CH COOH, is a-amino-P-para-hydroxyphenyl- NH2 C6H4- OH propionic acid. (The student will appreciate the naming of some of these sub- stances after he has studied the sections devoted to aromatic chemistry.) H / Tryptophan, H-C C--C-CH2 -CH. COOH II II H-C C C-H NH2 \c/ \N/ H H is a-Amino-,8-indolepropionic acid. CH2-S-S-CH2 Cystine, CH- NH2 CH.NH2 COOH COOH is di-(P-thio-a-aminopropionic acid.) CH2 -COOH Aspartic acid, CH COOH, is aminosuccinic acid. NH2 CH2 - COOH CH2 Glutamic acid, I , is a-aminoglutaric acid. CH-COOH NH2 CH2. CH2. CH2. CH2. CH-COOH, Lysine, I I NH2 NH2 is a, e-diaminocaproic acid. 142 PROTEINS HN Arginine, \C -NH- CH2 CH2 CH2 - CH - C00H, /NH2 NH2 is a-amino- -guanidino-valeric acid. CH NH N Histidine, I I CH=C- CH2. CH. COOH NH2 is a-amino-o-imidazolepropionic acid PROTEINS Proteins are essential, and in many ways, the most charac- teristic constituents of protoplasm. They may be regarded as combinations of a-amino acids. Their chemical properties are dependent upon the presence of these amino acids. Their physical properties, on the other hand, are largely due to the fact that they form colloidal solutions. Among the three classes of foodstuffs, fats, carbohydrates and proteins, the proteins alone contain the element nitrogen, and, as a rule, sulfur. The average percentage composition of proteins is (in per cent) C= 53, 0= 23, N= 16, H= 7, and S= 1. They may be classified as follows: Albumins.-Soluble in water and coagulated on boiling. (Examples: ovalbumin in egg white, lactalbumin in milk, serum albumin in blood, etc.) Globulins.-Insoluble in water, but soluble in dilute solutions of a number of salts (such as sodium chloride) and coagulable on heating. (Examples: serum globulin in blood, edestin in hempseed, ovoglobulin in egg white, etc.) Protamines.-Basic substances forming stable salts with mineral acids. In comparison with some of the other proteins, these yield relatively few amino acids on hydrolysis. They are soluble in water and not coagulated on heating. (Examples: salmine in salmon sperm, and in general, in the heads of ripe spermatozoa and in ova.) 143 AMINO ACIDS AND PROTEINS Histones.-Somewhat similar to protamines. These are soluble in water and precipitated by ammonia. (Examples: globin in hemoglobin, scombrone in mackerel sperm, thymus histone, etc.) Glutelins.-Proteins common in the vegetable kingdom. These are insoluble in neutral solvents, but soluble in acids and alkalies. (Example: glutenin in wheat.) Prolamines.-These are also common in the vegetable king- dom. They are soluble in 70-80 per cent alcohol (which dis- tinguishes them from glutelins and other proteins), but, like other proteins, insoluble in absolute alcohol. They are also insoluble in water and neutral solvents. (Examples: zein in corn, gliadin in wheat and rye, hordein in barley, etc.) Albuminoids.-These are found in the skeletal and connec- tive tissue of animals, and are characterized by their far greater insolubility in reagents than other proteins. (Examples: keratin in hair, collagen in connective tissue, etc.) The proteins which have so far been enumerated are known as " simple proteins," to distinguish them from the following " conjugated proteins ": Nucleoproteins.-These are combinations of protein and nucleic acid, and are characterized by yielding purine bases (p. 149) on hydrolysis. (Examples: nucleoprotein in thymus, pancreas, spleen, and in glandular tissue in general. They are found in nearly all cells, and particularly in the nuclei of cells.) Glycoproteins.-Combinations of protein and a compound containing the carbohydrate group. They are characterized by yielding, on hydrolysis, a sugar which reduces Fehling's- Benedict solution. (Examples: mucin in saliva, osseomucoid in bone, tendomucoid in tendon, etc.) Phosphoproteins.-These proteins, like the nucleoproteins, are rich in phosphorus, but, unlike the latter, do not yield purine bases on hydrolysis. (Examples: casein in milk, vitellin in egg yolk, etc.) Hemoglobins.-Combinations of protein with a pigment- containing substance. (Example: hemoglobin in blood, which on hydrolysis yields the histone, globin, and the iron-containing substance, hematin.) In addition to these, we have a number of " secondary " or "hydrolyzed " proteins, obtained in the course of hydrolysis 144 PROTEINS of proteins when acted upon by certain enzymes, acids or alkalies. They are: Metaproteins.-These represent the first stage in protein hydrolysis. They are soluble in acids and alkalies, but insoluble in neutral solvents (from which they are coagulated on boiling). Proteoses.-The primary proteoses are soluble in water, not coagulated on boiling, and precipitated by one-half saturated solution of ammonium sulfate. The secondary proteoses show similar properties, except that they require a completely satu- rated solution of ammonium sulfate for precipitation, a crude distinction, it must be confessed. Peptones.-These are similar to the proteoses, but are not precipitated by ammonium sulfate. As hydrolysis proceeds, we arrive at the polypeptide stage (compounds of a somewhat simpler type, chemically, than peptones), and finally obtain the individual amino acids. Composition of Proteins.-The various proteins, when com- pletely hydrolyzed (by acid, alkali or enzyme) yield amino acids. The essential difference among proteins is in the number and in the amount of amino acids which they yield. Up to the present, about eighteen of these amino acids have been isolated (see amino acids, p. 146), and the extent to which they occur in a number of proteins is given in the table on the following page. The isolation of the various amino acids is a laborious task and cannot be discussed here. Constitution of Proteins.-Emil Fischer has shown that the proteins may be regarded as combinations of amino acids, linked in the following way (to take the simplest case): CH2. CO OH CH2- COOH CH2 - CO-NH CH2 • COOH NHI2 H NH NH2 Glycine Glycylglycine Glycylglycine (dipeptide) is the simplest example of a poly- peptide. It, in turn, may combine with another molecule of glycine to form diglycylglycine (tripeptide). CH2 - CO-NH - CH2 - CO-NH - CH2 - COOH NH2 145 146 AMINO ACIDS AND PROTEINS PER CENT OF AMINO ACIDS ISOLATED FROM VARIOUS PROTEINS 0 oP Valine....... 0 21 4.3 4 5 2 50 ..... .......... 1.0 7.95 1.4 Cd CCd C Cd Glycocoll..... 0.02 0.00 0.45 0.00 0.0035.00 0.0016.5 0.4525.75 Alanine...... 2.00 0.00 1.6 2.22.....22.6 4.2 0.8 1.85 6.58 Valine........0.21 4.3 4.5 2.50.................1.0 7.95 1.4 Leucine...... 5.61 0.0015.3 10.71 8.78 0.7 29.0 2.1 9.7 21.38 Proline....... 7.0611.0 3.7 3.56 2.28 0.7 2.3 5.2 7.63 1.74 Phenylalanine. 2.35 0.0 1.9 5.07 4.90 1.3 4.2 0.4 3.88 3.89 Asparticacid.. 0.58 0.0 2.5 2.20 3.47 1.3 4.4 0..56 1.77 Glutamicacid. 42.98 0.0 17.2 9.1014.88 0.07 1.7 1.8821.77 0.76 Serine ........ 0.13 7.8 1.1 ? .......... 0.6 0.4 0.5 Cystine...... 0.45 0.0 7.5 ? .......... 0.3 0.0 0.07 ? Tyrosine ..... 1.20 0.0 3.6 1.77 1.95 9.7 1.3 0.00 4.5 Arginine...... 3.1687.4 2.7 4.91 7.38 ..... 5.4 7.62 3.81 0.3 HIistidine..... 0.61 0.0 ? 1.71 2.02 ..... 11.0 0.4 2.5 Lysine....... 0.00 0.0 0.2 3.76 5.77 ..... 4.3 2.75 7.62 Am monia..... 5.1 ..... ? 1.34 1.C8 ............... 1.61 Tryptophan... Pres. 0.0 .......... Pres ...... Pres. 0.0 1.5 and so on. Of course, the combinations need not involve glycine only, but other amino acids may take a part in such reactions- in fact, any substance containing the NH2 and COOH groups; so that the number of such possible polypeptides is very large. Fischer has prepared an octadecapeptide, consisting of three leucine and fifteen glycine units, which is not easily distinguish- able from a protein found in nature. Apart from being a colloid, this octadecapeptide is hydrolyzed by the enzyme trypsin (of the pancreas) into amino acids, just like any of the common proteins. As further evidence of the polypeptide nature of proteins, it should be recalled that when proteins are hydrolyzed, poly- peptides (such as glycyltyrosine) have actually been isolated from among the hydrolytic products. General Reactions.-Biuret.-When the protein is mixed with a cone. solution of sodium hydroxide and a drop or two of dilute copper sulfate solution is added, a violet to pink color is obtained. (Generally the simpler the protein the more pinkish PROTEINS the color, so that peptones show a distinct pink and albumins a distinct bluish-violet.) The reaction is given by nearly all sub- stances containing two O H -C-N-- groups attached to one another, to the same nitrogen atom, or to the same carbon atom. The name " biuret " is derived from the fact that biuret (which is obtained by heating urea, p. 114) gives this reaction. Xanthoproteic.-Heating a protein solution with cone. nitric acid produces a yellow color. This is changed to orange on the addition of an excess of ammonium hydroxide. (The yellow color is dependent upon the formation of a nitro compound.) Millon's.-Heating with Millon's reagent (essentially, mer- cury dissolved in nitric acid), a brick-red color or precipitate is obtained. (This reaction is given by phenol and phenolic deriva- tives.) The substance in the protein molecule responsible for this test is probably tyrosine. Glyoxylic acid (Hopkins-Cole).-When the protein is mixed with glyoxylic acid and cone. sulfuric acid added, a violet ring is obtained. (This reaction is due to the presence of tryptophan in the protein molecule.) Molisch.-With alpha-naphthol and cone. sulfuric, the pro- tein solution forms a violet ring. (The reaction is due to the presence of the carbohydrate glucosamine in the protein molecule.) (While no one of these color tests is evidence of the presence of a protein, any substance which gives two or more of these tests may be suspected of being a protein.) The following reactions are further confirmatory tests. Proteins are precipitated by the salts of heavy metals, such as lead acetate, mercuric chloride, copper sulfate, etc. The proteins are precipitated by the " alkaloidal reagents," such as phosphotungstic, phosphomolybdic, tannic, picric acids, etc. Proteins are precipitated by strong alcohol. Many of the proteins, like the albumins and the globulins, are coagulated on heating. (" Argyrol," a protein-silver combination, is used in con- junctivitis, laryngitis, etc.) 147 148 AMINO ACIDS AND PROTEINS READING REFERENCES TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), Chap. 29 (Proteins). PLIMMER-The Chemical Constitution of the Proteins. OSBORNE-The Vegetable Proteins. HARROw-Eminent Chemists of Our Time. (1920), pp. 217-239 (Fischer). CHAPTER XV NUCLEOPROTEINS, PURINES, URIC ACID AND PYRI- MIDINES Nucleoproteins are a group of combined proteins of especial interest to us, since, on the one hand, they are principally con- stituents of the nuclei of cells (animal and plant), and on the other, they yield, on decomposition, a group of important organic substances (purines and pyrimidines). They may be extracted from animal or vegetable sources by water or dilute alkali, and precipitated by acid (for example, the nucleoprotein in yeast may be extracted with dilute alkali and then precipitated by acid, or the lymphatic glands of the ox or sheep, or the thymus of a calf, may be extracted with water, and the nucleoprotein precipitated with acid.) A careful study of the hydrolytic products of nucleoproteins shows that they, like the proteins and higher carbohydrates, " split up " in stages. The following is a schematic repre- sentation: Nucleoprotein Protein Nuclein Amino acids Protein Nucleic a Amino acids cid (nucleotld) Phosphoric acid Nucleoside Carbohydrate Purine and pyrimidine bases The nucleoprotein, in other words, may be regarded as a combination of protein and nucleic acid, the latter, in turn, 149 INTRODUCTION this phenomenon is very little known in inorganic chemistry. For example, when we write HN03 we have reference to nitric acid, and to nitric acid alone, but when we write C2H60 this may stand for ethyl alcohol or for methyl ether, and the only way we can distinguish the one from the other is by writing graphic or structural formulas (p. 24), which give some idea of the arrange- ment of the atoms within the molecule. That is the reason why graphic and structural formulas are used so extensively in organic chemistry (pp. 14, 263). Importance and Applications.-We have already mentioned the fact that more than 225,000 compounds are grouped under organic chemistry. Many of these find various applications in our daily life. Some of them are so common that merely mentioning their names will suggest to the student many of their applications. Picking a few of these substances more or less at random, we may refer to starch, sugar, fats, oils, proteins, paper, artificial silk, soap, explosives, photographic developers, anesthetics, disin- fectants, antiseptics, dyes, drugs, waxes, ether, natural gas, per- fumes, glue, citric acid, alcohol, saccharin, artificial food colors, caffeine, cellulose, camphor, rubber, flavoring essences, gasoline, vaseline, coal tar, glycerine, aniline, indigo, salvarsan, etc. And it may be added that the various transformations which the foodstuffs and cellular tissue undergo in the plant and animal kingdom, involving complex syntheses and decompositions, are essentially those which can best be studied by the organic chemist. Other Sciences Based on Organic Chemistry.-Physiological (or Bio-) chemistry (which deals with the chemical processes that take place in animals and plants), food chemistry, and organic analysis, all have their basis in organic chemistry. Various aspects of medicine, dentistry and pharmacy require training in organic chemistry. We shall illustrate this inter-dependence with a few examples. A problem of general importance in bacteriology is to find some substance which has the property of destroying a certain type of bacteria without at the same time injuring the body tis- sues. Ehrlich, the German physician, who was also a trained chemist, found a cure for syphilis by the use of arsphenamine (p. 323) (also called salvarsan and " 606 "), which he synthesized in the laboratory. More recently the work of Jacobs and Heidel- berger at the Rockefeller Institute, N. Y., on the application of URIC ACID AND PYRIMIDINES being a combination of phosphoric acid, carbohydrate (usually a pentose if the carbohydrate is of plant origin, and a hexose if of animal origin), and pyrimidine bases. Among the common pyrimidines are uracil, thymine and cytosine. Pyrimidine itself has the formula: 1 N CH 6 2 CH CH 5 3 N-CH 4 and uracil, thymine and cytosine have the following structures: H-N-C=O H-N-C=O I I I i H-N-C-H H-N-C-H Uracil Thymine or or 2, 6-diketopyrimidine 2, 6-diketo-5-methylpyrimidine or 5-methyl uracil N=C-NH2 O=-C C-H H-N-C-H Cytosine or 6-amino-2-ketopyrimidine Among the purine bases are adenine, hypoxanthine and guanine. Purine itself has the formula: 1 N==6 C-H 1 1 7/H H-2 C 5 C-N 8 H 1 \C-H 3 N-4 C-N 9 and the structures for adenine, hypoxanthine, guanine and xanthine are: N==C-NH2 H-N--C--O I I H I H I-C C--N I-C C-N 1I i1 \C--H i (I C-H N-C-N// N-C--N'/ Adenine Hypoxanthine or or (-anmiliopurine 6-ketopurine 150 NUCLEOPROTEINS H-N-C=O NH2-C C--N \ II C-H N-C-N// Guanine or 2-amino-6-ketopurine H-N-C=O I c-H O=C C-NI \C-H H-N-C-N Xanthine or 2, 6-diketoptirine The purines are very largely oxi(lized to uric acid in the body: IHT-N-C===O O=C C-N I II C==O I--N-C--N Uric acid or 2, 6, 8-triketopurine (also called 2, 6, 8-trioxypurine) Uric acid is an important nitrogenous constituent of the urine. It is present in the joints, bladder, and in abnormally high amounts in the blood of persons suffering from gout and rheu- matism. We shall give one of several syntheses of uric acid. This will illustrate not only the synthetic preparation of an important purine derivative, but incidentally that of a pyrimidine deriva- tive, namely, a methyluracil: C113 -C- OH + H INH-CONH2 - II Urea CH. COOC2H5 Acetoacetic ester CH3 C -NH. -CO NH2 Hydrolysis CH3 C- NH CONH2 1 H1 -H20 CH-COOC2H 5 (acid) CH-CO OH H Ethyl--uramido- -UTramidorotonic (dehyd. crotonate acid agent) agent) NH-CO I I CO CH I I NH-C-CH3 4-Methyluracil HNO3 (Oxid. and nitration) NH-CO CO C.NO2 I I NH-C-COOH 5-Nitrouracilic acid Boiled > with water (-CO2) 151 URIC ACID AND PYRIMIDINES NH-CO I I CO C-NO2 NH-CH 5-Nitrouracil With tin and HC1, part of the 5-nitrouracil is reduced to the corresponding 5-amino-compound (5-aminouracil) and part of it to 5-hydroxyuracil: NH-CO CO C-OH I II NH-CH This compound is oxidized by bromine water to 4,5-dihy- droxyuracil, which, when heated with urea and H2S04, yields uric acid: NH-CO NH-CO I I I I CO C- OH H NH\ H2S04 CO C-NH SII + CO - I . 1 CO NH-C-I OH H NH/ NH-C-NH 4, 5-Dihydroxyuracil Urea Uric acid The oxidation of uric acid may yield any one of the following products (depending on the reaction and the reagent employed): NH2 CO CO-NH NH-CH-NH>C Allantoin NH-CO CO NH-CO Parabanic acid NH-CO .CO CO NH-CO Alloxan NH2 CO/ \NH2 Urea Alantoin occurs to a small extent in human urine, but in mammals,-other than man and anthrapoid apes it takes the place of uric acid, it being the principal end product of purine metabolism. 152 ALLANTOIN Other important purine derivatives are: CH3- N-CO I I CO C-N. CH3 and II CH CH3. N- C--N/ Caffeine or theine or 1, 3, 7-trimethyl-2, 6-diketopurine or 1, 3, 7-trimethylxanthine HN-CO I I CH3 CO C--N/ 1 \CH CHa N- C--N Theobromine or 3, 7-dimethyl-2, 6-diketopurine or 3, 7-dimethylxanthine Theobromine is present in cocoa beans (chocolate) and theophylline (isomeric with theobromine) occurs in tea leaves, while caffeine is a constituent of coffee (about 1 per cent) and tea (about 1-4 per cent). Caffeine, theobromine and theophylline are strong diuretics, but caffeine is peculiar in having a strong excitant action upon the central nervous system. READING REFERENCE JONEs-Nucleic Acids. 153 CHAPTER XVI CYANIDES, ISOCYANIDES AND OTHER NITROGEN COMPOUNDS THE student having taken inorganic chemistry is already familiar, to some extent, with cyanide compounds. He has used potassium ferrocyanide and potassium ferricyanide in testing for iron salts; and he remembers potassium cyanide and hydrogen cyanide as examples of deadly poisons. Cyanogen (CN)2, is a colorless, poisonous gas, with a pungent odor, and burns with a blue flame, giving carbon dioxide and nitrogen. It may be prepared: 1. By heating ammonium oxalate with a dehydrating agent: COONH4 P205 C-N I > I + 4H20 COONH4 Hydrolysis C=N (The cyanogen can be hydrolyzed back to the ammonium oxalate.) 2. By heating mercuric cyanide: Hg(CN)2 --2 Hg + (CN)2 Hydrogen Cyanide, HCN (also called hydrocyanic acid), is a colorless, poisonous volatile liquid, burning with a violet flame. Its water solution is called " prussic acid." (Some attempt was made during the war to use it as a " poison gas.") It occurs in bitter almonds, wild cherry bark and other plant products. It is a very weak acid. Its formula may be represented as H--C-N :- H-N=C. It may be prepared by heating sodium cyanide with sulfuric acid: NaCN + H2S04 -- HCN + NaHS04 a reaction quite analogous to the preparation of the halogen acids. Hydrogen cyanide hydrolyzes to formic acid: HCN + 2H20 -- H-COOH + NH3 ALKYL CYANIDES and reduces to methylamine: HCN + 2H2 --+ CH3 -NH2 It is used in medicine (a 2 per cent solution) in respiratory diseases and to quiet a cough. Recently, it has been recom- mended as a fungicide and insecticide (spraying trees). Ships are very often disinfected with HCN gas. Cyanogen Chloride, CN- Cl, is a poisonous liquid of low boiling point, and was used as a " poison gas " in the late war. It may be prepared by the action of chlorine on hydrogen cyanide: HCN + CICl --+ Cl-C=N + HC1 Recently it has been recommended to replace HCN for disin- fecting purposes. Cyanamide, CN NH2, is prepared by the action of ammonia on cyanogen chloride: CN-jCl + H[NH2 - CN NH2 + HCl (Calcium cyanamide, CN.NCa, made by heating calcium carbide and nitrogen, CaC2+N2 - CaCN2+C, finds extensive use as a fertilizer, for in the presence of water it decomposes in the soil, liberating ammonia: CN-NCa + 3H20 -- 2NH3 + CaC03 The calcium cyanamide of commerce (CaCN2+C), goes under the name of " nitrolime.") ALKYL CYANIDES, R-C_N Nomenclature.-CH3CN may be called either methyl cyanide, or cyanomethane, or acetonitrile. The -C-N is the " nitrile " group, and the name of the substance depends upon the acid obtained when the substance is hydrolyzed. For example, CH3CN is acetonitrile because it hydrolyzes to acetic acid. Similarly, C2H5 CN is propionitrile. Preparation.-1. The action of NaCN on an alkyl halide; e.g., CH31I + Na CN -> CH3CN + NaI 155 156 CYANIDES, ISOCYANIDES, NITROGEN COMPOUNDS 2. Heating the corresponding amide in the presence of a dehy- drating agent: e.g., (P205) CH3CONH2 - H20 ---- CH3CN Properties.-The alkyl cyanides are reactive on account of their unsaturated character (a triple linkage): CH3-CEN + H20 -- CH3CONH2 + H20 -> CH3COONH4 Acetamide Ammonium acetate CH3 CN + 2H2 ~ CH3 CH2 NH2 Ethylamine ALKYL ISOCYANIDES, R-N=CK, (or R-N.C) Nomenclature. CH3. N=CK may be called methyl iso- cyanide, methyl isonitrile or methyl carbylamine. (C2H5- N=C < is commonly spoken of as " carbylamine.") In organic cyanides the R is connected to the carbon atom: R-C--N whereas in the organic isocyanides the R is connected to nitrogen: R-N=C\ (A) . [The formula (A) is selected because the isocyanides are highly reactive substances, forming, among other things, addi- tive compounds.] Preparation.-1. Action of silver cyanide on alkyl halide; e.g., RC1 + AgNC -- RNC + AgC1 (which suggests that silver cyanide may exist in one of two forms, either as AgCN or AgNC). 2. The reaction of a primary amine with chloroform in an alkaline solution; e.g., CH3NH2 + CHC13 + 3KOH -- CH3NC + 3KC1 + 3H1120 (This is a test for primary amines. See p. 134.) Properties.-The isocyanides are colorless, poisonous liquids, with an extremely disagreeable and characteristic odor. They are very reactive; e.g., OTHER NITROGEN COMPOUNDS R-N=C/ R-N==C/ .+ HCl + C12 R.N=C + S R*N==C + 0 --+ R-N=-CH R--N=C/C1 Cl -* R-N=C=S R-N=C==O (The C in R N=C seems to be very reactive and, therefore, unsaturated.) (In this connection, it may be of interest to point out here that the reactivity of carbon monoxide is in reality due to the divalency of its carbon atom, e.g., Cl C=0 + Cl2 - C-O0 \cl Phosgene or C=O + O -+ C02 whereby the divalent carbon is transformed into the tetravalent form.) To distinguish between the cyanide and the isocyanide, it is merely necessary to hydrolyze the compounds: R CN + 2H20 -- R-COOH + NH3 R--N=-C + 2H20 -- R'NH2 + H-COOH OTHER NITROGEN COMPOUNDS R-O-C-N Alkyl cyanate R-N=C==O Alkyl isocyanate R-S-C=N Alkyl thiocyanate R-N=C==S Alkyl isothiocyanate Isocyanic acid, HNCO, is an unstable liquid, but a polymer, cyanuric acid (HNCO)3 is known. R C-:N Alkyl cyanide R -N=C< Alkyl isocyanide 157 158 CYANIDES, ISOCYANIDES, NITROGEN COMPOUNDS RNCO compounds are prepared thus: RI + AgNCO -- RNCO + AgI Silver cyanate Fulminic Acid, C=NOH, is a poisonous, very unstable liquid. Here again we have a divalent carbon represented. C-N-0O Mercuric fulminate, CHg, and silver fulminate, C=N-OAg, are prepared when the respective metals are acted upon by nitric acid and alcohol. They are used as detonators in percussion caps to explode gunpowder, dynamite, T.N.T., and other explosives. Allyl isothiocyanate, CH2=CH - CH2 N=C==S, is present in black mustard seeds and is used in medicine as a powerful rube- facient and counterirritant. It is employed as a substitute for the mustard plaster. 0 0 Nitro Compounds, R-NN/ The nitro group is -N, . 0 These may be looked upon as nitric acid, HO-N// in which the OH is replaced by R. The aliphatic nitro compounds are not important, but the aromatic ones are, as we shall see later (p. 218). The nitro compounds, R-N4 , are isomeric with the alkyl nitrites, R-O-N=O, which have already been dis- 0 cussed on p. 95. For example, nitroethane, C2H5-N/O is isomeric with ethyl nitrite, C2Hs-0-N=--O, though it differs 0 from ethyl nitrate, C2H5-O-N\O The nitro compounds may be prepared by the action of silver nitrite on halogen compounds; e.g., C2H51I + Ag NO02 - C2Hs5N02 + AgI NITRO COMPOUNDS 159 They are easily reduced to the corresponding amines; e.g., C2H5 N02 + 3H2 > C2HsNH2 + 2H20 Ethylamine The nitroso group is represented by -N=O; e.g., CH3\ CH3 CH3---C-N--O H N-N=--O CHa/ CH3/ Nitrosotrimethylmethane Nitrosodimethylamine ELEMENTS PRESENT IN ORGANIC COMPOUNDS 5 various arsenical compounds to medicine, holds out hope that one of these will prove of distinct value in the treatment of sleeping sickness. Mention may also be made of the use of " chloramine-T" (p. 266) and other organic compounds containing chlorine, in the treatment of infected wounds. During the war, Dakin and Carrel found that " chloramine-T," given under certain conditions is strong enough to destroy micro-organisms, without at the same time harming the tissues. Another problem, this time of particular importance to physi- ologists and general medical practitioners, is the isolation, in a chemically pure state, of the active principles of glands in the body. One of the active principles of the adrenal glands, adre- naline (or, as it is someties called, " epinephrine ") has not only been isolated from the gland, but has actually been synthesized in the laboratory. In this work Abel of Johns Hopkins and the late Takamine, a Japanese chemist who had established himself in the United States, took leading parts. Lately, the active principle of the thyroid gland, thyroxin, has been isolated by Kendall of the Mayo Clinic in Rochester, Minn., who has also succeeded in synthesizing it. And we may mention that insulin, (" iletin ") an active principle of the pancreas, which has been shown by the Canadian, Banting, to play such an important r6le in diabetes, though known so far in an impure form, is receiving much attention from organic chemists. Cocaine, novocaine, butyn, benzyl alcohol and ethylene as anes- thetics; the essential constituents of chaulmoogra oil in the treat- ment of leprosy; caffeine and related substances as diuretics; barbital (veronal) and luminal as hypnotics; thymol and carbon tetrachloride as a cure for hookworm; are only a few illustrations of the comparatively recent developments in the application of organic chemistry to medicine. Elements Present in Organic Compounds.-Numerous as the compounds of carbon are, most of them contain but two to five different elements in the molecule. There are hundreds of com- pounds which contain merely the elements carbon and hydrogen. These are known as hydrocarbons. Methane (CH4), benzene (C6H6), naphthalene (CloHs) and anthracene (C14H1o), are examples. Many contain the element oxygen in addition to car- bon and hydrogen; as for example, the sugars, fats, starches, alcohols, ethers, acetic acid and glycerol. Many are composed CHAPTER XVII CARBOHYDRATES AND RELATED COMPOUNDS THE name carbohydrate (carbon hydrate) is derived from the fact that compounds belonging to this class contain C, H and 0, the H and 0 being in the proportion of 2 : 1, respectively (as in water). There are, however, substances other than carbohy- drates, such as acetic acid, (CH3 COOH), and lactic acid (CH3 - CHOH COOH), which contain H and 0 in the propor- tions such as are found in water. On the other hand, a number of compounds belong to the carbohydrates although the pro- portion of H to 0 is not 2 : 1; e.g., rhamnose (C6H1205). The more modern view is to regard carbohydrates as con- taining aldehyde-alcohol or ketone-alcohol groups; or compounds which upon hydrolysis are converted into substances containing such groups. Carbohydrates are mainly derived from the vegetable king- dom. Physiologically, the carbohydrates represent one of the three great classes of foodstuffs. Many of them are also of extreme importance in the industries. In general, carbohydrates fall into two main classes; the sweet and crystalline compounds, called sugars; and the taste- less and non-crystalline compounds, termed starches, celluloses and allied products. Carbohydrates are classified into: 4. Monosaccharides (no further hydrolysis with dilute acids): Diose, as glycolaldehyde, CH20H. CHO. Trioses, as glyceraldehyde, CH20H CHOH - CHO or dihydroxyacetone, CH2OH. CO - CH20H. Tetroses, as erythrose, etc. Pentoses, as arabinose, xylose, ribose, etc. Hexoses, as glucose, mannose, galactose, fructose, sorbose, etc. PENTOSES AND HEXOSES B. Disaccharides (yield two monosaccharides upon hydrolysis). Sucrose, maltose, lactose. C. Trisaccharides (yield upon hydrolysis three monosac- charides): Raffinose. D. Polysaccharides (yield upon hydrolysis more than three monosaccharides): Starch, cellulose, dextrin, glycogen, inulin, gums, pectins, pentosans, etc. (The ending " ose " generally refers to carbohydrates.) The monosaccharides, or simple sugars, are aldehydes or ketones linked directly to carbon with OH group as H-C-OH H-C-OH H-C=-O C=--O An aldose I (hydroxy-aldehyde) CH2 CH20H A ketose (hydroxy-ketone) The trioses and tetroses are of theoretical rather than practical importance. The pentoses, C5H1005, are important plant products, and are sometimes found in human urine. Ribose is a constituent of nucleic acid (p. 149), obtained from yeast. Arabinose may be obtained by the hydrolysis of gum arabic, cherry gum, etc., and xylose, by the hydrolysis of straw and various forms of cellulose. Extremely important, from our point of view, are the hexoses, the disaccharides and some of the polysaccharides. Among the hexoses, C6H1206, d-glucose (also called dextrose) is the most important. It is present in the juice of many sweet fruits, such as grapes (hence grape-sugar). It is a normal, and very necessary constituent of blood, and, in pathological con- ditions (as in diabetes), accumulates to an abnormal degree in the blood and in the urine. Commercially, glucose is prepared by the hydrolysis of starch in presence of dilute acids. (CoHloO5)x + X-H20 -f X-'CH1206 It may be obtained from many poly- and disaccharides. Since 162 CARBOHYDRATES AND RELATED COMPOUNDS it rotates the plane of polarized light to the right, it is also called dextrose. Its formula may be written: CH20H CHOH CHOH CHOH CHOH C=O H Some indication of how we arrive at such a structural formula may be given. In the first place, elementary analysis and molecular weight determinations give us the empirical formula CGH1206. The substance behaves like an alcohol, because it reacts with acetyl chloride or acetic anhydride to form acetyl derivatives: R-O H + Cl OC-CH3 -> R-OOC-CH3 Since glucose forms a penta-acetyl derivative, it must contain five OH groups. On reduction, glucose first yields the corre- sponding alcohol, and ultimately (if HI is used) a normal six- chain iodohydrocarbon, proving glucose to contain a normal chain of carbon atoms: CH20H CH20H CH3 CHOH CHOH CH2 CHOH H2 CHOH CH2 CHOH CHOH CHI CHOH CHOH CH2 C=O CH20H CH3 \T Sorbitol 3-Iodohexane Glucose forms a cyanohydrin with HCN: C1120H CH2OH (UHOH)4 + HCN --* (UHOH)4 \H I CN OH and an oxime with hydroxylamine, NH20H: CH2OH CH20H (CHOH)4 (C4HOH)4 I + H20 C==jO + H21NOH C=NOH \H \H proving the presence of a carbonyl, CO, group (see p. 72). The presence of this group may be further shown by the reaction of glucose with pheny1hydrazine: CH20H CH2OH (HOH)8 (HOH)3 CHOH - C[ HJOJH + H2N.IINHC6H51 C=l0 + H2 N-NH-C6H5 C=N-NH-C6H5 \H Phenyihydrazine Glucose Glucose phenylhydrazone (+ NH3 + C=N-NH-CGH5 H C6H5NH2) Aniline CH20H (CHOH)3 + H2NNHC6H5 > C==N-NHC6H5 C=N-NHCH5 H Phenylglucosazone -H2 HEXOSES 163 164 CARBOHYDRATES AND RELATED COMPOUNDS It now merely remains to determine the position of the CO group. This can be done in the following way: Glucose is com- bined with HCN and the resulting product hydrolyzed (see p. 82). CH20H CH20H CH20H I I CHOH CHOH CHOH CHOH10 CHOH CHOH I HCN I 2H20 CHOHI > CHOH - CHOH I I CHOH CHOH CHOH C-O C-OH CHOH H H CN COOH The hydroxy acid is a normal, seven-carbon compound. The COOH group must be attached to the sixth carbon atom, and this, in turn, must have contained a CO group to have reacted with HCN. But the sixth carbon atom in glucose is the end carbon atom; therefore, the position of the CO group in glucose must be at the end carbon atom. If we have gone into the constitution of glucose at some length, it is merely to illustrate the methods used in assigning formulas to the various carbohydrates. Properties of Glucose.-Like all carbohydrates, glucose reacts with the Molisch reagent (a-naphthol) and cone. H2SO4 to give a violet ring or color, a reaction said to be due to the formation of CH-CH II iI furfural, CH C-CHO (see p. 310). It forms an osazone with \o/ phefiylhydrazine, a reaction already discussed. These osazones are of the utmost importance in the identification of a number of sugars, since they show definite crystalline forms and have definite melting points. Owing to the presence of the CHO group, glucose reduces ammoniacal silver solutions and the alkaline solutions of a number of metals, such as copper, bismuth, and mercury. The best known of these reactions is the Fehling's PROPERTIES OF GLUCOSE test, which consists in heating glucose with a solution of copper sulfate, to which potassium hydroxide and Rochelle salt have been added; a yellowish red precipitate of cuprous oxide is obtained. (The theory of the reaction may be explained thus: in the absence of a reducing agent, such as glucose, the cupric hydroxide that is first formed would be converted to black cupric oxide: Cu(OH)2 --> CuO + H20 but when glucose, or any other appropriate reducing agent is present, cuprous oxide, Cu20, which is yellow to red in color, is formed instead: 2Cu(OH)2 -- Cu20 + 2Hi20 + 0 Benedict has modified the Fehling reagent by mixing the copper sulfate with sodium citrate and sodium carbonate, producing a reagent which does not deteriorate even after long standing. The Benedict modification also has the advantage over Fehling's solution in that, when it is applied to test for glucose in the urine, neither uric acid nor creatinine-nitrogenous substances present in the urine-interfere with the test; nor does chloroform, which is often used as a preservative for the urine.) (The original Fehling's solution consists of two separate solutions: (a) 34.65 grams of copper sulfate per 500 cc. of water; and (b) 125 grams of potassium hydroxide and 173 grams of Rochelle salt dissolved per 500 cc. of water. These solutions are preserved separately and mixed in equal volumes when needed for use. Benedict's first modification consists of (a) 34.65 grams of copper sulfate per 500 cc. of water; and (b) 100 grams of anhy- drous sodium carbonate and 173 grams of Rochelle salt per 500 cc. of water. These solutions are mixed when needed. Benedict's second modification consists of but one solution: 17.3 grams of copper sulfate, 173 grams of sodium citrate and 100 grams of anhydrous sodium carbonate per liter of water. For the quantitatire determination of glucose, Benedict's solution consists of 18 grams of crystallized copper sulfate, 200 grams of crystallized sodium carbonate-or 100 grams of the anhy- drous salt-200 grams of sodium or potassium citrate, 125 grams of potassium thiocyanate'and 5 cc. of a 5 per cent solution of 165 166 CARBOHYDRATES AND RELATED COMPOUNDS potassium ferrocyanide-all dissolved and made up to 1 liter of solution.) Heated with picric acid, in the presence of KOH, glucose gives a red color-a reaction which forms the basis for a colori- metric determination of glucose in blood. (The reaction is said to be due to the reduction of picric (p. 263) to picramic acid; H2/(NO2)3 (NO2)2 CoH2 -- C6H2-NH2 OH \OH though the question has not been definitely settled.) Yeast "ferments " glucose forming ethyl alcohol and C02: C6H1206 -> 2C2H5OH + 2C02 Glucose is optically active, turning the plane of polarized light to the right. It has four asymmetric carbon atoms. Glucose (both in the solid and in the form of syrup, as corn syrup) is used extensively in making confectionery, jellies, preserves, as table syrups, in the manufacture of alcoholic beverages, as a diluent (to increase bulk and weight) for dyes, in chewing gum, tobacco, etc. On oxidation, glucose may give rise to the following products: CH20H CH20H CHO COOH I I I I (CHOH)4 --> (CHOH)4 -- (CHOH)4 -- (CHOH)4 CHO COOH COOH COOH Gluconic acid Glycuronic acid Saccharic acid (Glycuronic acid is of importance physiologically, since it may combine with poisonous substances, such as phenol, chloral, etc., to make them inert.) The optical activity of freshly prepared glucose solution diminishes on standing. This " mutarotation," as it is called, is due to the fact that there are, in reality, two forms of glucose, a- and 0-glucose present, having different rotatory powers, and the optical activity of the resulting mixture will depend upon the amounts of each present. The a-glucose is readily changed to #-glucose, and vice versa, until equilibrium is reached. GLUCOSIDES Glucosides.-When glucose reacts with methanol in presence of HC1, two compounds, a- and P-methyl glucosides are obtained, the formulas of which may be represented thus: CH20H CH20H H-C--OH HCOH S\\ HO-C-H\ HOCH 0 --* 0 HCOH / HCOH / 1/ / H-C--OH + HO CH3- H-C-OCH3 Lactone formula a-Methyl glucoside of glucose CH20H 1 0 HOCH / HCOH / CHaO3-C-H a-Methyl glucoside The two glucosides have different physical properties. They also behave differently towards enzymes. Maltase hydrolyzes the a- variety, but not the #-, and emulsin hydrolyzes the P-, but not the a-. The naturally occurring glucosides belong to the 0-form. On hydrolysis, glucose and other products are produced. The following glucosides occur in nature: phloridzin, found in the bark of fruit trees, which yields fructose and phloroglucinol when hydrolyzed. Phloridzin is often used to induce a form of diabetes in animals. Salicin, CH4\ 5, on hydrolysis yields glu- \CH20H cose and saligenin, or salicyl alcohol. Salicin occurs in willow CN bark. Amygdalin, CoHs-CH/ , hydrolyzes to two \O - C12H21010 molecules of glucose, HCN and benzaldehyde. It is found in bitter almonds. Arbutin, CH4 C1105 , hydrolyzes to glu- \OH cose and hydroquinone. It is present in the leaves of the berry tree. Myronic acid is present in black mustard seed. On hydrolysis, it is converted to dextrose, KHS04 and allyl isothio- cyanate (C3H5 - NCS). Ruberythric acid is present in madder 168 CARBOHYDRATES AND RELATED COMPOUNDS root. On hydrolysis or fermentation, it is converted to the dye alizarin and glucose. CH20H (CHOH)3 Glucosamine, , a substance closely related to glucose, CH . NH2 CHO is an important constituent of glycoproteins, such as mucin and the various mucoids, and may be obtained from them by hydroly- sis. It is also present in chitin, a constituent of the shells of the lobster. Glucosamine reduces Fehling's solution, and its general properties are much like those of glucose. Galactose is an aldohexose, like glucose: CH20H (CHOH)4 CHO It is obtained by the hydrolysis of lactose or milk sugar. It is also an important constituent of the cerebrosides of the brain. Like glucose, it forms an osazone with phenylhydrazine (differing, however, in structure), and reduces Fehling's solution, but fer- ments slowly with yeast. On oxidation, it forms mucic acid (stereoisomer of saccharic acid), which also differentiates galac- tose from glucose. Fructose, or levulose, or fruit-sugar, has the formula: CH20H (CHOH)3 CO CH20H and is, therefore, a ketohexose, isomeric with glucose and galac- tose. Fructose, glucose and galactose are, physiologically, the three important hexoses. Fructose is a constituent of cane- sugar, or sucrose, from which it may be obtained on hydrolysis. Like the other two common hexoses, fructose reduces Fehling's solution and forms an osazone. The osazone with phenylhy- SUCROSE drazins is the same as the one formed with glucose. It may be distinguished from glucose and galactose by the Seliwanoff test, which consists of heating fructose with resorcinol dissolved in dilute HC1, whereby a red color and a red precipitate are obtained. i-Fructose, C6H111206, is obtained by polymerization of six moles of formaldehyde with calcium hydroxide. A mixture of sugars is obtained known as "formose " from which i-fructose has been isolated. i-fructose is the racemic (dl) form. Sucrose, or cane sugar, C12H22011, is one of three physiologically important disaccharides, the other two being, lactose and maltose. On acid hydrolysis, sucrose yields a mixture of glucose and fructose (" invert sugar "). The same result is brought about by the enzyme sucrase, found in the small intestine. On a large scale, sucrose is obtained from sugar-cane, sugar-beet, etc. Unlike dextrose, fructose, galactose, maltose and lactose, five other important sugars, it does not reduce Fehling's solution, nor does it form an osazone-that is, it does not behave like an aldehyde or ketone sugar. To explain this, the suggested formula for sucrose does not contain a " free " CO group: CH20H CH20H CHOH CH--- CH----- CHOH I 0 I 0 CHOH CHOH I I CHOH C C / CH20H Fructose part H Glucose part When sugar is heated above its melting-point, caramel is formed. This is a brown substance and is used extensively as a coloring material in food preparations. (Whether the sugar is obtained from the sugar-cane or the sugar-beet, the principle involved in the extraction process consists in first separating the juice from the insoluble fiber, next in precipitating albuminous material and neutralizing the VLLUANDEF D) LOWY JR., M,i ~ P-fITbL;UR.Ari 'iJ, P.-f. INTRODUCTION of carbon, hydrogen and nitrogen, as hydrocyanic acid and aniline. Examples of compounds containing carbon, hydrogen, oxygen and nitrogen are some of the alkaloids, indigo and urea; and those containing carbon, hydrogen and a halogen are chloroform and iodoform. Often, in addition to the elements already mentioned, we find sulfur and phosphorus. Many of the proteins contain appre- ciable quantities of the former element, and the phosphatides, such as lecithin and cephalin, which are important cellular con- stituents, contain phosphorus. (It may be mentioned in passing that quite recently Hopkins has isolated a substance from cells, to which he has given the name " glutathione," which contains sulfur and which is regarded as a substance that plays a very important r6le in all cellular oxidations.) Elements in addition to those already mentioned are often met with. Following the pioneer work of Ehrlich on salvarsan, very many organic compounds of arsenic, antimony, bismuth and mercury have been prepared. Quite recently an organic com- pound of lead, lead tetraethyl, has been used to prevent " knock- ing " in automobiles (p. 187). Many salts of organic acids, such as those of sodium, potassium, calcium, etc., are found in nature or may be prepared in the laboratory. Sources of Organic Compounds.-A. Some organic compounds may be traced either to the plant or animal kingdom. Out of carbon dioxide, water and various constituents from the soil, in the presence of light, the plant builds a veritable galaxy of sub- stances: sugars, starches, cellulose, alkaloids (morphine in opium- nicotine in tobacco), acids (citric and tartaric), salts (" tartar " in grapes), esters (flavoring substances of fruits), essential oils (peppermint, lemon), camphor, vegetable oils (linseed, cotton- seed, olive), herbs (from which drugs are made and which were so largely used in days. gone by), gum arabic, flavoring substances (vanilla), dyes (indigo, logwood, fustic) perfumes, tannin (from nutgalls), etc. B. Plants and animals furnish us with fats, proteins, carbohy- drates, enzymes and vitamins, and we often go to the animal kingdom for a number of products, such as urea, uric acid, gelatin, toxins and antitoxins. C. Destructive Distillation of Coal.-When soft coal is strongly heated in a retort, this complex substance breaks down into a 170 CARBOHYDRATES AND RELATED COMPOUNDS acids present, and finally in evaporating the filtrate and separating the crystals from the mother-liquor. The latter contains some 50 per cent of sucrose and is known as " molasses," a product used in the making of alcohol. If the "molasses " is derived from the sugar-cane, it may be used as table syrup and in the preparation of rum.) Lactose, C12H22011, or milk sugar, occurs in milk to the extent of about 4 per cent. On hydrolysis, or by the action of the enzyme lactase in the small intestine, it yields glucose and galac- tose. Since it reduces Fehling's solution and forms an osazone, we assume that it contains a " free " CO group: CH20H CH2 CHOH HOH CIHI O CHOH / I / CHOH / CHOH 0 1 / SCHOH CHOH \C - C=o H H Maltose, C12H22011, or malt sugar, is found in malt, which is the sprouted grain of barley. This sprouted grain contains an enzyme, diastase, which converts the starch in the grain into maltose. A similar action occurs in the body when the enzyme ptyalin, found in saliva, acts on the starch in foods. When maltose is hydrolyzed by acids, or by maltase (an enzyme found in yeast and also in the small intestine) two molecules of glucose are obtained. (The maltase in yeast, acting on maltose, forms glucose, and then the zymase in yeast, acting on glucose, produces ethyl alcohol and CO2.) Maltose behaves similarly to lactose, but the latter forms galactose as one of its products of hydrolysis, whereas maltose forms only glucose. Raffinose, C18H32016, is a trisaccharide occurring in cotton seed, etc. It does not reduce Fehling's solution. On hydrolysis, it yields fructose, glucose and galactose. This hydrolysis may either be brought about by acids or by certain bacteria and yeasts. CELLULOSE Chitin, a tetrasaccharide, is probably composed of four glucosamine (p. 168) units. It is prepared from the shells of lobsters or crabs. Chondroitin, another tetrasaccharide, is contained in cartilage, often in combination with protein. Starch, one of a number of polysaccharides having the general formula (C6HloO5),, is widely distributed in the vegetable kingdom. It is synthesized in the plant by the combined action of carbon dioxide and water in the presence of chlorophyll. It is hydro- lyzed in the body first to soluble starch, then to a number of dextrins, then to maltose and finally to glucose, and in the latter form is absorbed into the blood stream. Boiled with water, the granules swell and burst, and " starch paste " is obtained. Starch gives a blue color with iodine. Dextrins of the general formula (CHloO5)z, are considered somewhat less complex than starch itself, for the dextrins are obtained in the course of the hydrolysis of starch by enzymes. Erythrodextrin gives a reddish-brown color with iodine and achrodextrin fails to give any color. Glycogen, or " animal starch " (C6H1o005), is found almost exclusively in the animal kingdom, and particularly in the liver. It is the form in which carbohydrate is stored in the body. With iodine it gives a red color. Inulin is a polysaccharide found in the tubers of the artichoke, dahlia, etc. Unlike starch, it is soluble in hot water and gives a negative reaction with iodine. On hydrolysis, it yields the monosaccharide levulose. Cellulose, (C6HoO5)., is the chief constituent of the cell wall of plants. Cotton fiber is almost pure cellulose, or " normal " cellulose. When hydrolyzed, cellulose yields glucose. Ligno- cellulose is probably a combination of cellulose with gums and resins, while pectocellulose is a combination of cellulose and a substance, pectin, the latter being responsible for the formation of jellies from fruit. Cellulose is, chemically, highly inert. It may be dissolved (possibly with some changes) in Schweitzer's reagent (ammoniacal solution of copper oxide). Acetyl derivatives may be obtained with glacial acetic acid, and acetic anhydride, showing cellulose to contain OH groups. Industrially, cellulose is of immense importance. It is the 172 CARBOHYDRATES AND RELATED COMPOUNDS chief ingredient of cotton, linen, hemp, etc., and of paper (which in turn, may be made from cotton and linen rags or from wood). Parchment paper is cellulose treated with conc. sulfuric acid. Mercerized cotton is cotton treated with sodium hydroxide solution, whereby the cotton is converted into a stronger fiber with a glossy appearance somewhat resembling silk. It takes dyes more readily than cotton. Artificial silk is a better imitation of silk than is mercerized cotton, and may be obtained from nitrated cotton (a mixture of the lower nitrocelluloses), or from " viscose " (cellulose dissolved in a mixture of CS2 and NaOH solution) or from cellulose acetate. With nitric acid cellulose forms various nitrate compounds. The higher nitrates (hexanitrate), such as gun-cotton (insoluble in alcohol-ether mixture), are explosives; and the lower nitrates are used in. the manufacture of celluloid. Pyroxylin, a mixture of lower cellulose nitrates, is used in preparing lacquers and making artificial silk and celluloid. It is soluble in amyl acetate and methanol. Collodion, similar to pyroxylin in composition, is used for photographic films, as a protective covering for wounds, etc., and in the making of dialyzing bags. It is soluble in an alcohol-ether mixture. Celluloid is made by subjecting pyroxylin and camphor to heat and pressure. Cordite, a smokeless powder, is made by treating gun-cotton and nitroglycerine with acetone and some vaseline. Mannans, Galactans, Hemicellulose, etc.-These substances, present in the seeds of numerous plants, resemble cellulose, but dissolve in dilute alkali and on hydrolysis yield not only glucose (as cellulose does) but other hexoses as well. Gums, Pectins, Mucilages.-These are also polysaccharides containing pentose and hexose groups. The gums are probably carbohydrates combined with acids. Some are soluble, and others insoluble, in water. Gum arabic, gum tragacanth, etc., are used as vehicles to suspend insoluble substances in aqueous mixtures. Mucilages form " viscous " liquids with water. The gelatinization of fruit extracts is due to the pectin present. READING REFERENCES TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), chap. 24 (Vegetable Fiber and Products from Cellulose); chap. 28 (Sugar). READING REFERENCES 173 SADTLER-Chernistry of Familiar Things. (1915), chap. 19 (Paper and Textiles). FINDLAY-Chemistry in the Service of Man. (1916), chap. 5 (Cellulose and Cellulose Products). DUNCAN-The Chemistry of Commerce. (1907), chap. 11 (Cellulose). SLossoN-Creative Chemistry. (1920), chap. 6 (Cellulose); chap. 7 (Synthetic Plastics); chap. 9 (The Rival Sugars); chap. 10 (What Comes from Corn). PHILLIP-Romance of Modern Chemistry. (1910), chap. 20 (Sugar and Starch). IRVINE-The Constitution of Polysaccharides. Chemical Reviews, 1, 40 (1924). ROGERS-Manual of Industrial Chemistry. (1921), pp. 866-897 (Sugar); pp. 898-917 (Starch, Glucose, Dextrin and Gluten); pp. 1033-1047 (The Art of Paper Making); pp. 1048-1069 (The Cellulose Industries). ARMSTRONG-The Simpler Carbohydrates and Glucosides. MACKENZIE - The Sugars and Their Simple Derivatives. SURFACE-The Story of Sugars. BRowN-Forest Products. (1919), chap. 18 (Maple Syrup and Sugar). CHAPTER XVIII FOODSTUFFS AND THEIR CHANGES IN THE BODY THE foodstuffs may be divided into carbohydrates, fats, proteins, mineral salts, water and vitamins. Some include oxygen in the list because of the very necessary part it plays in the oxidation of the foodstuffs in the body. We may dismiss the mineral salts, water and vitamins, because, so far as we know, they undergo no chemical changes preparatory to their absorp- tion by the blood and tissues. We will confine ourselves to the carbohydrates, fats and proteins, because they do undergo profound chemical changes in the digestive tube and after they have left the digestive tube and enter the liver and various tissues of the body. The fats and carbohydrates are ultimately oxidized to carbon dioxide and water, and eliminated as such. -The proteins, aside from being oxidized to carbon dioxide and water, also form a number of nitrogenous products which appear chiefly in the urine, such as urea, uric acid, creatinine, etc. These nitrogenous products really represent incomplete stages in the oxidation of the protein, for the complete oxidation of protein would yield carbon dioxide, water and nitrogen. Complex substances of the types of fats, proteins and carbo- hydrates are not immediately oxidized in the body to carbon dioxide, water, and relatively simple nitrogenous substances; there must be a number of intermediate steps in the process. During the past few years, organic and physiological chemists have been very busy tracing these steps. While there is still much to be elucidated, much has already been done, and a brief resum6 of the work accomplished will be given here. For those desiring a more detailed account we must refer them to the references at the end of the chapter, particularly to Dakin's masterly monograph. Carbohydrates.-The digestible carbohydrates are all broken down to monosaccharides before absorption. The enzyme 174 CARBOHYDRATES ptyalin (in saliva), amylopsin (in pancreatic juice), sucrase, maltase and lactase (in intestinal juice) hydrolyze the more complex carbohydrates to the hexoses,-glucose, levulose and galactose (p. 161). These are then absorbed through the walls of the small intestine, pass into the blood, thence to the liver, and there are synthesized to glycogen (p. 171) and stored as such. Whenever fuel is needed by the body, the glycogen reserve is called upon, and the glycogen is hydrolyzed to glucose, but this time to glucose only. Then this glucose is oxidized in the tissues to-ultimately-carbon dioxide and water. It is believed that the first step in the oxidation of glucose is the splitting of the glucose molecule into two three-carbon molecules. It was believed at one time that the most probable three-carbon compound to be formed was lactic acid, since this substance is always produced by working muscle; but the view more generally held now is to regard either glyceraldehyde, CH20H - CHOH* CHO, or pyruvic aldehyde (methyl glyoxal) CH3 . CO. CHO, as the first step in the decomposition of glucose, and lactic acid as a by-product obtained either from glycer- aldehyde or pyruvic aldehyde. So that we may represent the first steps thus: C6H1206 -- 2CH20H. CHOH CHO Glucose Glyceraldehyde or C6H1206 - 2CH. CO - CHO + 2H20 Pyruvic aldehyde and lactic acid could then be formed in one of two ways: Glucose --> CH20H CHOH - CHO Glyceraldehyde CH3aCO -CHO -- CH3-CHOH COOH Pyruvic aldehyde Lactic acid or, still better, Glucose --> CH3 - CO - CHO --, CH3 CHOH. COOH (The action of alkali on glucose has been shown to yield the products mentioned in these reactions. Further, using surviving liver tissue, it has been possible to convert both pyruvic aldehyde and glyceraldehyde into lactic acid; and in diabetes, where the mechanism of the cell is disturbed, glyceraldehyde, pyruvic alde- hyde and lactic acid have all been shown to produce glucose.) 175 176 FOODSTUFFS AND THEIR CHANGES IN THE BODY True oxidation probably comes into play at this point; that is to say, with the conversion of either pyruvic aldehyde, or lactic acid, into pyruvic acid; CH3 CO -CHO Pyruvic aldehyde CH3- CO- COOH CH3 - CHOH - COOH/ Pyruvic acid Lactic acid Now it has been shown that in the organism, a-ketonic acids (of which pyruvic acid is an example) are changed into the fatty acid with one less carbon atom; in this case into acetic acid. It seems probable that the intermediate step here is acetaldehyde. (In this connection, it may be mentioned that yeast juice ferments pyruvic acid into acetaldehyde and carbon dioxide.) So that the steps are probably CH3 CH3 CH3 I I I CO -* CHO --+ COOH Acetaldehyde Acetic acid COOH Pyruvic acid The acetic acid is finally oxidized to carbon dioxide and water. Summarizing the various steps: Glucose Glyceraldehyde - Pyruvic aldehyde z- lactic acid Pyruvic acid Acetaldehyde Acetic acid Carbon dioxide and water Fats.'-The straight fats, that is to say the glyceryl esters of stearic, palmitic and oleic acids (p. 99), are hydrolyzed in the digestive tract into glycerol and fatty acids. (Some fatty acid 1 The lipoids, such as lecithin and cholesterol (p. 104) often associated with fat in food, undergo changes in the body which are either too complex, or too little understood to be discussed here. is also converted into soap, due to the alkalinity of the medium.) This is mainly brought about by the enzyme lipase (in the pan- creatic juice), which, in turn, is very actively assisted by the "bile salts," the sodium glycocholate and sodium taurocholate (found in bile). The fatty acids and glycerol, immediately after absorption through the walls of the small intestine, are synthe- sized back again into fats, and as such pass from the lacteals into the lymph, into the thoracic duct, and thence into the general circulation. The fat not needed for immediate use is largely stored in the adipose tissues. The preliminary step in the oxidation of fats is probably one of hydrolysis into glycerol and fatty acid. It may be assumed that the glycerol is first oxidized to glyceraldehyde, which would then, of course, follow the usual scheme of carbohydrate oxida- tion (p. 175). The oxidation of the fatty acid part of the mole- cule probably takes place in accordance with a theory first advanced by Knoop and known as Knoop's " P-oxidation theory." According to this view, the fatty acid is first attacked in the P-position, being changed to a hydroxy and then to an oxy (keto) acid. The a and P carbon atoms (with their hydrogen atoms) are probably next oxidized to carbon dioxide and water, leaving a fatty acid containing two less carbon atoms. Then the process is repeated until finally carbon dioxide and water are produced. At each stage of the process, two carbon atoms are removed, so that, if we start with stearic acid, containing Cls atoms, we pass to palmitic, C16, then to C14, etc. To illustrate the process, let us assume, that we have reached the C6 stage with caproic acid. The changes can be illustrated as CH3 CH3 CH3 CH3 I I I I CH2 CH2 CH2 CH2 I I I I CH2 CH2 CH2 CH2 pCH2 CHOH CO COOH I I I Butyric aCH2 CH2 CH2 acid I I I COOH COOH COOH Caproic P-Hydroxy f-Keto caproio acid caproic acid acid FATS 177 178 FOODSTUFFS AND THEIR CHANGES IN THE BODY CH3 CH3 CHOH CO I I CH2 CH2 CH3 I - I -* C + H COOH COOH COOH #-Hydroxy Acetoacetic Acetic butyric acid (diacetic acid acid acid) In diabetes, the poisonous "acetone bodies" or "acid bodies " which are so often produced, are derived from fats. These " acetone bodies " include butyric acid, P-hydroxy butyric acid, acetoacetic acid and acetone. The acetone is a by-product obtained probably from acetoacetic acid by the loss of C02.--It would seem as if the diabetic has not only difficulty in oxidizing glucose, but also in completely oxidizing fats; the fats in his case are oxidized to the four-carbon stage and no further. Kahn, working with the knowledge that the naturally-occurring fats all contain an even number of carbon atoms, and stimulated by Knoop's theory that fatty acids are oxidized in such a way as to lose two carbon atoms at each stage, has synthesized an odd- carbon fat-from margaric acid, C16H33 COOH, a C17 acid-, which, when given to the diabetic, is said not to produce " ace- tone bodies," because in the oxidation of this odd-carbon fat, the four-carbon acids are avoided; thus C17 -C15 C1 C13 --+ C11 C9 - C7 -- C5 -- C3 - C1 Proteins.-The proteins I are hydrolyzed in the digestive tract by the enzymes pepsin (in gastric juice), trypsin (in pancreatic juice) and erepsin (intestinal juice). The final hydro- lytic products are amino acids (p. 146). The amino acids are absorbed as such, and either finally pass into the tissue to form tissue protein, probably in some such way as outlined in Fischer's synthesis of polypeptides from amino acids (p. 145), or are eliminated principally in the form of urea, by a process of " de-amination," which occurs very largely in the liver, but may also occur in other tissues. This process of " de-amination " is essentially the splitting off of the NH2 group from the amino 1'We refer here to the "simple" proteins (p. 143). The "conjugated" proteins (p. 144) present many difficulties. PROTEINS acid. Dakin has shown that an a-amino acid, in water, under- goes spontaneous dissociation into the corresponding a-ketonic aldehyde and ammonia; so that if we take alanine as an example of an a-amino acid, we would get CH3 CH3 CH NH2 --+ NH3 + CO COOH CHO Alanine Pyruvic aldehyde The pyruvic aldehyde would then most probably be further oxidized according to the scheme outlined under carbohydrates. (This, by the way, explains how proteins may also serve as a source of energy; and it also suggests how, in cases of diabetes, the carbohydrate is formed from protein.) The ammonia com- bines with carbonic acid, a constant product of metabolism, to give ammonium carbonate, which; by a process of dehydration, is finally converted into urea: NH40 - H20 NH2 - H20 NIH2 N40C=0 NH40C0 ---> NH2>C=O NHO> NH4O> NH2 Ammonium Ammonium Urea carbonate carbamate It has already been mentioned that in the urine we find nitrogenous products other than urea. Since protein is the only one of the three classes of foodstuffs which contains the element nitrogen, it is reasonable to assume that these nitrogenous products are of protein origin. Even under normal conditions a small quantity of ammonia (in the form of ammonium salts) is eliminated. We also find uric acid and purine bases, which are obviously.derived from the nucleoproteins of the food (or body tissues) and the purine substances, such as are found in meat, for example (see p. 150). An appreciable amount of creatinine, and, to a less extent, creatine (see p. 114), is also found in the urine. The probable interrelationships of protein, fat and carbo- hydrate in the body.-The connecting links between protein and carbohydrate have already been indicated. They will be shown schematically here: 179 SOURCES OF ORGANIC COMPOUNDS number of (chemically) simpler substances. The conversion of a complex substance into a number of simpler substances by the aid of heat (in the absence of air) is known as " destructive distilla- tion." The destructive distillation of coal yields coal gas (illumi- nating gas), ammonia, coke and coal tar. Coal tar, at one time dis- carded as a useless by-product, is now the starting-point for any number of organic products (some 225 compounds have been so far isolated). Out of coal tar we get benzene, toluene, naphthalene, anthracene, carbolic acid, the cresols, etc.; and these substances (the source of many aromatic compounds, see pp. 199), in turn, yield thousands of other organic compounds, many of them of great value as dyes, perfumes, drugs, etc. (see chart, p. 199). Perkin, an Englishman, was the first (in 1856) to prepare a coal- tar dye, but the development of the dye industry is due largely to the Germans, who, prior to the late war, were responsible for much research work in this field. Post-war developments in this country and in England have already reached such a stage as to ensure the establishment of permanent dye and other related industries. D. Destructive Distillation of Wood.-The important products obtained from wood are acetic acid, methanol (wood alcohol), acetone, wood tar, combustible gases and charcoal. E. Destructive Distillation of Bones.-This yields animal char- coal (bone black) and bone oil, out of the latter of which a number of nitrogenous compounds, characterized by their disagreeable odor, are obtained (pyridine and quinoline are examples). F. Fractional Distillation of Petroleum.-A mixture of two or more liquids having different boiling-points may usually be sepa- rated from one another by a process of distillation, the liquid with the lower boiling-point distilling over first. A process which separates two or more liquids by making use of their different boiling-points is called " fractional distillation." The fractional distillation of petroleum yields a number of important commercial products, such as naphtha, gasoline, kerosene, gas oil, lubricating oil, cylinder oil, vaseline, etc. G. Fermentation.-It was for a long time supposed that in the conversion of sugar into alcohol by means of yeast, the living cells of the latter were primarily responsible for the change. We now know that what brings about this change is not the cells them- selves, but substances produced by the cells, known as " enzymes." 180 FOODSTUFFS AND THEIR CHANGES IN THE BODY Glucose Protein Glyceraldehyde Pyruvic aldehyde A Amino acids including Alanine Pyruvic acid Acetaldehyde Acetic acid C02 + H20 What are the connecting links between fats and carbohy- drates? How are we to explain that an excess of carbohydrate is so easily deposited in the form of fat? The glycerol part of the fat is obviously connected with the gylceraldehyde from glucose: Oxid. Glycerol z=t Glyceraldehyde Reduc. But how are we to suggest the possible formation of a complex fatty acid from the glucose molecule? It has been suggested that the synthesis may be along the lines of an aldol condensation (p. 76). Starting with acetalde- hyde, a product formed in the oxidation of glucose, two mole- cules of the aldehyde may condense to give: CH3CHO + CH3CHO -+ CH3 CH(OH) CH2 CHO B-Hydroxy butyraldehyde which may then combine with another molecule of acetaldehyde to give a 6-carbon compound, and so on, until the C16 or C1s is reached. By simultaneous reduction and oxidation, or the transfer of the oxygen attached to the 0-carbon to the end carbon, the hydroxy aldehyde may be converted to the normal, satu- rated acid. Another theory, largely due to Miss Smedley, and based on sound experimental evidence, may be summarized as follows: Pyruvic acid and acetaldehyde-both products formed in the oxidation of glucose-condense thus: CH3CHO + CH3 -CO COOH-->CH3. CH: CH CO COOH + H20 FAT AND CARBOHYDRATE IN THE BODY The ketonic acid is next converted into its aldehyde and car- bon dioxide in a manner similar to the conversion of pyruvic acid to acetaldehyde (p. 176). (A) CH3 CH: CH- CO- COOH --, CH3-CH: CH-CHO + CO2 This aldehyde has two more carbon atoms than the acetalde- hyde with which we started; it now condenses with another molecule of pyruvic acid, forming a ketonic acid with more car- bon atoms; and so on. The oxidation of the unsaturated ketonic acid (A) yields an unsaturated acid with one less carbon atom: CH3 CH : CH. CO. COOH + O --- CH3 CH : CH.COOH + C02 By reduction we obtain a fatty acid containing two more carbon atoms than the aldehyde from which we started. READING REFERENCES DAKIN-Oxidations and Reductions in the Animal Body. LUSK-The Science of Nutrition. (1917), chaps. 6 (Protein) and 9 (Carbohydrate). SHERMAN-Chemistry of Food and Nutrition. (1918), chap. 5 (Fate of Foodstuffs in Metabolism). BAYLIss-Principles of General Physiology. (1915), chap. 9 (Nutrition). MATHEws-Physiological Chemistry. (1916), chaps. 18 (Carbohydrate) and 19 (Protein). HARRow-What to Eat In Health and Disease. SADTLER-Chemistry of Familiar Things. (1915), chaps. 13 (Food Elements), 14 (Individual Foods), 15 (Animal Feeding), 17 (Chem- istry of the Body). DuNcAN-Some Chemical Problems of Today. (1911), chap. 4 (Chemical Interpretation of Life). CALDWELL and SLossoN -Science Remaking the World. (1923), pp. 247-264 (Chemistry and Economy of Food). 181 CHAPTER XIX SULFUR, PHOSPHORUS, ARSENIC AND ORGANO- METALLIC COMPOUNDS SULFUR COMPOUNDS SULFUR is just below oxygen in the periodic table, two elements should, therefore, show close relationships. abundant evidence of such structural relationships in chemistry. An entire series of analogous compounds formed by substituting sulfur for oxygen in organic con ROH Alcohol RSH Mercaptan or thioalcohol They are called mercaptans for they compounds (corpus mercurium captans.). RO Metal RS Metal Alcoholate Thioalcoholate or mercaptide ROR R-S-R An ether or Alkyl sulfide alkyl oxide or a thioether HO-OH H--S-S--H or or H202 H2S2 as in Na2S2 R-C H Aldehyde RK >C=O Ketone R-C/ Thioaldehyde R R>C s Thioketone 182 CH3SH Methyl mercaptan or methyl thioaicohol combine with mercury C2H5SNa Sodium ethyl mercaptide C2H5-S-C2H5 Ethyl sulfide or ethyl thioether R-S-S-R Organic disulfide CH3-C ) Trithioacetaldehyde CH3 CH3> Thioacetone and the We find organic may be apounds. SULFUR COMPOUNDS In addition to these types of compounds we have: O NH2 O R-C H R--C R-S=O Thioacids Thioacid amides Alkanesulfonic acids, or alkyl sulfonic acids R-N=C=S Alkyl isothiocyanate and others, showing in every case the close analogy of these sulfur compounds to the corresponding oxygen ones. Many of these sulfur compounds may be prepared from their oxygen analogues by the use of phosphorus pentasulfide; e.g., 5R-O-R + P2S5 -- 5R-S-R + P205 Most of the compounds having the structure R-S-H and R-S-R have exceedingly putrid disagreeable odors and are poisonous. Mercaptans may be prepared: 1. By the action of potassium hydrogen sulfide on the halogen compound: e.g., C2H5 I + KISH -4 C2H5SH + KI 2. By the action of phosphorus pentasulfide on an alcohol; e.g., 5C2H50H + P2S5 --+ 5C2H5SH + P205 Mercaptans are converted to mercaptides thus: C2HsSH + KOH -- C2H5SK + H20 On oxidation, R-S-H (where the S is divalent) becomes R-S OH, an alkanesulfonic acid (where the S is hexavalent). Sulfides.-These may be prepared: 1. By the action of a thioalcoholate on the halogen compound: RIX + Na SR - R--S-R + NaX (Analogous to RI X + Na IOR - ROR- an ether- + NaX) 183 184 ARSENIC AND ORGANO-METALLIC COMPOUNDS 2. By the action of potassium sulfide on the halogen compound: 2RCl + K2S -- R-S-R + 2KC1 The thioethers on oxidation give, first, R-S=O, a sulfoxide, Ro / and then R , a sulfone. R R "0 Mustard gas (one of the most toxic gases used in the late war) IS CICH2- CH2 CH2CH2S , p'-dichloroethyl sulfide C1CH2. CH2 It was manufactured by passing ethylene into sulfur monochloride, CH2=CH2 CICH2-CH2\ + S2C12 - >S +S CH2=CH2 C1CH2-CH2/ Oil of garlic contains allyl sulfide: CH2=CH CH2 CH2--CH CH2 Sulfonal may be prepared from acetone by combining it with ethyl mercaptan in presence of a dehydrating agent and oxidizing the product with KMnO4: HC1 gas CH3 H SC2H5 CH3 0 H SC2H5 C ----+ CH3 c/SC2H5 Oxid. C3 SC2H5 CH3/ SC2H5 CH3 SC2H5 Acetone ethyl mercaptol Diethyldisulfone dimethylmethane or sulfonal Sulfonal has hypnotic properties and is used as a soporific. Trional is the ethyl derivative in place of one methyl group. The starting substance for its synthesis is C2H5'CO.CH3. PHOSPHORUS AND ARSENIC COMPOUNDS 185 Thioacetic acid, CH3COSH is prepared by the following reaction: CH3 COC1 + KSH -- CH3 COSH + KC1 Trithioacetaldehyde, (CH3-C 3 and thioacetone, CH3 \H >)CS, are prepared by the action of H2S on acetaldehyde CH3 and acetone, respectively. The alkane sulfonic acids (or alkyl sulfonic acids) of the type O R-S=O are not of particular importance in the aliphatic \OH series, but they are in the aromatic series. CH2-NH2 Taurine, or p-amino ethanesulfonic acid, O/0 , is a CH2-S=O OH constituent of taurocholic acid, which in the form of its sodium salt is an important constituent of the bile. 7SH Xanthic acid, C S , is the ethyl ester of dithiocarbonic \OC2H5 /SNa acid. Cellulose xanthate CS is produced when cel- \0 cellulose lulose is heated with CS2 and NaOH solution. This is the basis /NH2 for the "viscose" artificial silk. Thiourea, C=S , is the sulfur /NH2 \NH2 analogue of urea, C-O , which in turn is the principal nitrogen \NH2 end product in the metabolism of proteins in the body. Allyl isothiocyanate, CH2=CH-CH2--N=C=S, is present in mustard oil. PHOSPHORUS AND ARSENIC COMPOUNDS According to the periodic table, nitrogen, phosphorus, arsenic and antimony belong to the same family of elements. This implies that compounds of P, As and Sb, analogous to N com- pounds, should exist. These do exist. We have, for example, in inorganic chemistry: NH3 PH3 AsH3 SbH3 Ammonia Phosphine Arsine Stibine 186 ARSENIC AND ORGANO-METALLIC COMPOUNDS and in organic chemistry: (CH3)3N (CH3)3P (CH3)3As (CH3)3Sb Trimethylamine Trimethylphosphine Trimethylarsine Trimethylstibine (C2H5)4N-OH (C2H5)4P-OH etc. Tetraethylammonium hydroxide Tetraethylphosphonium hydroxide (The phosphorus compounds are, as a rule, more reactive than the corresponding nitrogen compounds). (A number of proteins, such as the nucleoprotein found in the nucleus of cells, the casein in milk, and the phosphatides-of which the lecithin of egg yolk and brain tissue is an example- contain the element phosphorus as an integral part of a complex molecule.) (See p. 104.) CH3As CH3 / \ Cacodyl oxide, 0, is obtained when arsenic tri- CH3 CH3 oxide and potassium acetate are distilled: As203 + 4CH3COOK --- (CH3)4As20 + 2K2C03 + 2C02 The name cacodyl-" stinking "-was given to the group (CH3)2As-by Bunsen, its discoverer. The cacodyl compounds are highly poisonous. The salts of cacodylic acid, (CH3)2As 0 \OH, as the sodium, calcium, iron and mercury cacodylates, are used in the treatment of syphilis, tuberculosis, malaria and pellagra. Ethyl dichloroarsine, C2H5AsC12, and CH==CH - AsC12, known I Cl as "Lewisite"-were used as war gases. The antimony compounds are similar in structure to those of arsenic. A number of very important arsenic compoul.ds will be dis- cussed under the aromatic series (p. 322). ORGANO-METALLIC COMPOUNDS ORGANO-METALLIC COMPOUNDS Various combinations of organic radicals with metallic ele- ments are known. The following are examples: + HBr In this reaction HX is eliminated; the H atom must be linked to a carbon in a ring, while the X atom must be linked to a carbon not in a ring. They may also be prepared by heating the salts of aromatic acids with soda lime-a reaction similar to one used in the prepara- tion of the paraffins (p. 18); e.g., COONa + NaO H - Na2CO3 Sodium benzoate or, by the elimination of the S03H group from benzene com- pounds (by the use of steam, in the presence of acids); e.g., SO3H + HO H - + H2SO4 Benzenesulfonic acid or, by distilling phenol with zinc dust; e.g., H-- +ZnO Phenol or phenyl hydroxide REACTIONS OF AROMATIC HYDROCARBONS General Reactions of Aromatic Hydrocarbons.-Aromatic compounds react with nitric acid, forming nitro derivatives; e.g., H ± HOI N2 - NO2 + 20 Nitrobenzene (This is known as nitration.) They also react with sulfuric acid forming sulfonic acids; e.g., H + HO O SO3H HO > j 10 + H20 Benzenesulfonic acid (This is known as sulfonation.) The "side chain," whether CH3 or any other group, may be oxidized to the carboxyl group, COOH; e.g., CH3 COOH Oxidation Toluene or Benzoic acid phenylmethane (These reactions-nitration, sulfonation and oxidation- bring out the essential differences of aromatic and aliphatic hydrocarbons.) Benzene, C6H6, is the mother substance of the aromatic hydrocarbons. Commercially, it is obtained from coal tar. It is also present in California petroleum. It is a colorless liquid (b.p. 80.40), burning with a smoky flame (due to the high per- centage of carbon), and when its vapor is mixed with air it is explosive. It is used as a solvent for fats, resins, etc., and in the manufacture of a large number of aromatic compounds; e.g., nitrobenzene, chlorobenzene, etc. Crude benzene (benzol) is used extensively in motor fuel. Benzene is a narcotic which 201 202 BENZENE AND THE AROMATIC HYDROCARBONS when swallowed or inhaled produces vertigo, delirium and convulsions. Preparation.-One method is to pass acetylene through a red hot tube: 3C2H2 -- C6H6 Here we have an example of how we can pass from an aliphatic to an aromatic compound-in this particular method, by " poly- merization:" H H-C C-H H-C C-H I H With nitric and sulfuric acids, and with chlorine (long exposure to sunlight) we get, respectively, nitrobenzene, benzenesulfonic H Cl H / H CI-C C-Cl acid and benzene hexachloride, I I ; chlorinated H-C C-H / \c/\ Cl Cl H Cl in the presence of iron, aluminium, iodine, etc. (catalysts or "carriers"), we get C1 Chlorobenzene CH3 Toluene, , or phenylmethane, or metnylbenzene, is RULES FOR SUBSTITUTION IN BENZENE RING 203 obtained from coal tar and also by the distillation of balsam of Peru and Tolu, b.p. 1110. (C6Hs5-monovalent-is known as the "phenyl " group.) It may be prepared by the Friedel-Craft synthesis which has already been given (p. 200). Its properties are similar to those of benzene. When oxidized, it yields benzoic acid (p. 201). Rules for Substitution in the Benzene Ring.-1. If any one of the elements or groups, F, Cl, Br, I, R, OH, OR, CH2X, NH2, NHR or NR2 (these contain single bonds) is present in the ring, an element or group that may next be introduced will take the p- and o- positions with respect to the first group. 2. If any one of the groups, NO2, S03H, CHO, COOH, CO R or CN (these contain double or triple bonds), is in the ring, an element or group that may next be introduced will take (largely) the m- position with respect to the first group. (The amounts of m-, p-, and o- products formed depend very largely upon such factors as temperature, concentration of reacting substances, the type of dehydrating agent, and other experimental factors.) (It is essential before the student proceeds any further with the text that he thoroughly master these rules.) An example of the application of these rules is immediately seen in the case of toluene. Toluene contains a methyl (R) group; hence, a second group will proceed simultaneously to the p- and o- positions; for example, CH3 CH3 CH3 HNO3 S(H2S04) > and as dedydrating agent / a o-Nitrotoluene NO2 p-Nitrotoluene CH3 CH3 CH3 ( H2SO4 -SO3H and SO3H o-Toluene- p-Toluene- sulfonic acid sulfonic acid 204 BENZENE AND THE AROMATIC HYDROCARBONS At low temperatures, the o- predominates, while at high tem- peratures the p-. Xylenes, or dimethylbenzenes.-Since these are di-substitution products, three isomers are known: CH3 CH o-Xylene m-Xylene They are obtained from coal tar. give the corresponding dibasic acids, the position of the CH3 groups: COOH -COOH 0- C2H5r Ethyl benzene, COOH CH3 p-Xylene On oxidation, the xylenes indicating at the same time COOH DH. 0 COOH , is an isomer of the xylenes, but is easily distinguished yields benzoic acid, from them by COOH 0* CH3 Mesitylene, --CH H3C oal tarH3 methylbenzene, is found in coal tar. the fact that on oxidation it 1, 3, 5 or symmetrical tri- CH Cymene, O , or p-methylisopropylbenzene, is found CH CH3 CH3 in oil of thyme, oil of caraway, oil of eucalyptus, etc. The number of hydrocarbons containing the benzene nucleus is large. Some are derived from coal tar, others are synthesized. A few of these compounds will be mentioned: CH=CH2 C=CH Phenylethylene or styrene 0CHCH 0 Symmetrical diphenyl- ethylene or stilbene Phenylacetylone C-C Diphenylacetylene or tolane Tetraphenylethylene -/ I H Diphenylmethane H Triphenylmethane CYMENE 205 206 BENZENE AND THE AROMATIC HYDROCARBONS H H 0C-C- Symmetrical diphenylethane / C- Iexaphenyletlhane (Gomberg, of the University of Michigan, in studying the action of zinc upon triphenylchloromethane, has obtained a substance, triphenylmethyl (C6H5)3-C, in which one of the car- bon atoms is apparently trivalent. (C6H5)3C-C(C6H5)3 ± 2(C;H5)3C. Since the structure of organic compounds is so intimately bound up with the view that the carbon atom is tetravalent, Gomberg's triphenylmethyl, with its trivalent car- bon atom, opens up many new lines of research.) Diphenyl Naphthalene Anthracene Phenanthrene The last three compounds mentioned belong to the " con- jugated " or condensed cyclic series, and will be taken up in detail in Chapter XXVIII. Hydroaromatic hydrocarbons are hydrogenated aromatic hydrocarbons; e.g., dihydrobenzenes: CH2 CH2 HC CH2 HC CH II I or 1I II ; HC CH HC (H tetrahydrobenzene CH CH2 HC CH2 I I HC CH2 CH2 CH2 and hexahydrobenzene or hexa- MOSES GOMBERG (1866- PROFESSOR OF CHEMISTRY AT THE UNIVERSITY OF MICHIGAN, IS ONE OF THE PIONEER WORKERS ON TRIVALENT CARBON AND FREE RADICALS (P. 206). 207 INTRODUCTION Many of the qualitative tests serve as the basis for the quan- titative determinations. The carbon dioxide and water formed by the oxidation of a compound containing carbon and hydrogen are collected and weighed, and from the amounts of the products formed, the percentages of carbon and hydrogen in the original compound are calculated. The nitrogen in a compound may either be determined by the " Kjeldahl " method, whereby the element is converted into ammonia, or by the " Dumas " absolute method, whereby nitrogen gas is set free and its volume measured. In the determination of the halogens, the compound is either oxidized with fuming nitric acid in presence of silver nitrate, the resulting silver halide weighed and the halogen calculated; or the compound is heated with pure calcium oxide, and the halogen in the resulting calcium halide determined either by precipitation or titration with silver nitrate. Sulfur in an organic compound is determined by heating with fuming nitric acid, thereby converting it to sulfuric acid. This is then precipitated as barium sulfate with barium chloride. The percentage of sulfur is calculated from the weight of barium sul- fate. For- estimating phosphorus and other elements, the methods outlined in inorganic quantitative analysis are followed. Neither in its detection nor in its determination is there a good method available for oxygen when present in an organic com- pound. The general procedure is to determine the percentage of all the other elements present in the compound, subtract the total from 100, and " call " the difference the per cent of oxygen. The principles underlying the analytical methods are quite simple, but the details for the quantitative determination of C, H, N and the other elements, are rather complex. The analysis just discussed is what is known as " ultimate " or " elementary " analysis. It refers to the precentage of the ele- ments present in the compound. There is still another type of analysis, known as " proximate," with which the clinical, phar- maceutical or food chemist has much to do. This " proximate " organic analysis deals with the determination of ingredients present in a mixture, such as the fat or protein in milk, or the various nitro- genous constituents and sugar in urine, or the percentage of alcohol in wine, etc. The quantitative analysis enables us to arrive at what is known 208 BENZENE AND THE AROMATIC HYDROCARBONS CH2 H2C CH2 methylene, I . The last is found in Caucasian petro- H2C CH2 CH2 leum. It and its homologues are known as the naphthenes. The hexamethylene may be prepared by the Sabatier and Send- eren's reaction (passing benzene vapor and hydrogen over finely divided nickel): CH2 H2C CH2 + 3H2 -- I IH 0 H2C CH2 CH2 A derivative of hexahydrobenzene, known as hexahydroxy- H OH H \/ H \/c\/ HO-C C-OH hexahydrobenzene, or inositol, I , is found in H-C C-H / \c/\ HO OH OH H heart muscle and other animal organs, but is present in larger amounts in unripe beans and peas. The empirical formula for this compound is C6H1206, and it has often been called a cyclic sugar, though in reality it possesses none of the common properties of the sugars. READING REFERENCES FINDLAY-The Treasures of Coal Tar. WARNEs-Coal Tar Distillation. TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), chap. 20 (Coal Tar). FINDLAY-Chemistry in the Service of Man. (1916), chap. 12 (Synthetic Chemistry). SLossoN-Creative Chemistry. (1920), chap. 4 (Coal Tar Colors). READING REFERENCES 209 CALDWELL AND SLossoN-Science Remaking the World. (1923), pp. 48-79 (The Influence of Coal Tar on Civilization). SLossoN-Chats on Science. (1924), No. 17 (How Scientific Inspiration Comes-Kekul6). GOMBERG-Organic Radicals. Chemical Reviews, 1, 91 (1924). ROGERs-Manual of Industrial Chemistry. (1921), pp. 554-587 (Coal Tar and Its Distillation). HARROw-Eminent Chemists of Our Time. (1920) pp. 1-18 (Perkin and Coal Tar Dyes). CHAPTER XXII HALOGEN DERIVATIVES, SULFONIC ACIDS AND NITRO COMPOUNDS OF THE AROMATIC HYDROCARBONS HALOGEN COMPOUNDS 1 THE halogens may react in one of three ways with aromatic hydrocarbons: (1) they may form addition products; e.g., H Cl H H 0 + 3C2 Cl-C C-Cl H-C ('-H H (Cl Benzene hexachloride or hclxac:hloroliexahydrobenzene (This needs exposure to sunlight, but no carrier or catalyst.) (2) Substitute in the side chain; e.g., CH3 CH2CI I ±C2 - + HCl Benzyl chloride 'At this point the student is advised to review the chapter on aliphatic halogen compounds, p. 40. HALOGEN COMPOUNDS -(This is accomplished at the boiling temperature of toluene, in the presence of sunlight, but in the absence of a catalyst or halogen carrier.) (3) The halogen may enter the ring; e.g., /CI3 + C2 - 1 o-Chlorotoluene CH3 and C1l p-Chlorotoluene (This needs ordinary temperature, no sunlight and a carrier.) The usual halogen " carriers " or catalysts, are FeCla, FeBra, AlBra, Fe, P, S, I, etc. Preparation.-The halogen derivatives of the aromatic series may be prepared by direct halogenation with Cl2 or Br2, as just described (iodine does not react), or by the conversion of the corresponding amino compound into the halogen derivative, where the halogen takes the place of NH2 :e.g., N1l2 0 0 (See p. 231 for further details of the reaction.) (Ethyl alcohol can be treated with hydrogen bromide, in the presence of sulfuric acid, to give C2H5Br, but when phenol, OH S is treated with hydrogen bromide, no analogous reaction CHa + HC1I 211 HALOGEN DERIVATIVES, SULFONIC ACIDS takes place. Again, when ethyl alcohol is acted upon by phos- phorus .pentachloride, PC15, we get C2H5Cl, but when phenol is C1 similarly treated, only a small yield of chlorobenzene, is obtained. On the other hand benzyl alcohol is readily trans- formed into benzyl chloride by PCl5: CH20H CH2CL Notice that here the side-chain reacts. The side-chain, in fact, behaves like an aliphatic, rather than like an aromatic compound.) Properties.-Where the X is attached to the ring, as in CH3 we get substances which may be colorless liquids or oCl solids, with an agreeable odor, and which are stable; where the X CH2C1 is attached to the side-chain, as in , the compounds have strong, disagreeable, pungent odors, are very reactive, and act as lachrymators. In general, they show the properties of the aliphatic halogen compounds of the type RX. 212 HALOGEN COMPOUNDS Some of the properties of the two types of halogen compounds may be summarized thus: CH2Cl Benzyl chloride CH20H Benzyl alcohol CH2NH2 Benzylamine CH2CN Benzyl cyanide CH3 p-chlorotoluene No reaction No reaction No reaction from which it may be seen that where the halogen is attached to the nucleus, we get a relatively inactive compound; but where it is attached to the side-chain a very active compound, similar in its properties to the aliphatic halogen derivatives, is obtained. (The Fittig reaction exemplifies a typical reaction for the type where the halogen is attached to the nucleus.) Whether the X is attached to the ring or to the side-chain, may be determined in some such way as the following: Reagents KOH NH3 KCN 213 HALOGEN DERIVATIVES, SULFONIC ACIDS CH3 C1 CH2CI () COOH Oxid. C1l p-Chlorobenzoic acid Benzoic acid Thousands of be mentioned: halogen compounds are known; only a few will Cl Br Cl Cl CH2C1 CH3 Br Cl I C1 I Chloro- p-Dibromo- p-Dichloro- p-lodochloro- p-Chloro- p-Iodo- benzene benzene benzene benzene benzyl toluene chloride Chlorobenzene is manufactured by chlorinating benzene in presence of iron. It is used for the manufacture of dye inter- mediates.1 p-Dichlorobenzene is used extensively to protect woolen goods from moths. We may again refer to the preparation of these halogen compounds. Toluene, when acted upon by chlorine-in the presence of sunlight, in the absence of a " carrier " and moisture, and at boiling temperature-gives the following products: 1 A dye intermediate is an organic substance used in the manufacture of dyes. 214 HALOGEN COMPOUNDS CH2C1 Cl2 H C CH3 C12 > + HC1 Benzyl chloride CHC12 + 2HCI Benzal chloride or benzylidene chloride Cl3 + 3HCI Benzotrichloride When, however, the chlorine and the toluene are made to react in the absence of sunlight and at room temperature, but in the presence of a carrier, we get: CH8 CH3 CH3 ACl C12 > +HC1 Cl o-Chlorotoluene p-Chlorotoluene CH3 CH3 Cl 01±012 C1 Cl Cl 2, 4, 6-Trichlorotoluene 2, 4-Dichlorotoluene 215 216 HALOGEN DERIVATIVES, SULFONIC ACIDS (A number of halogen derivatives of the aromatic series were used during the late war as poison gases. Some of these were benzyl bromide, C6Hs5 CH2Br, diphenylchloroarsine (C6HS)2As Cl, phenylcarbylamine chloride, C6H5-N=C= C12 and xylyl bromide, CH3. C6H4 -CH2Br. Since we are on the sub- ject of war gases, we may include a few other compounds also used during the late war, although they really belong to the aliphatic series: bromoacetone, CH2Br CO. CH3; bromoethyl methyl ketone, CH3. CO. CHBr -CH3; chloroacetone, CH2C0 CO CH3; nitrotrichloromethane-or chloropicrin-CCl3. NO2; dichlorodi- ethyl sulfide - mustard gas- (C2H4C1)2S; dimethyl sulfate (CH3)2S04; dichloromethyl ether, (CH2CI)20; phosgene, COC12; trichloromethyl chloroformate, Cl-COOCC13 and hydrocyanic acid, HCN.) SULFONIC ACIDS Sulfonic acids are a very important class of organic compounds, since from them phenolic compounds (p. 237), naphthols (p. 281), etc., are prepared. They are generally prepared by the direct sulfonation of the hydrocarbon; e.g., H HO 0 -S=O HO>1 Benzenesulfonic acid CH3 CH3 CH3 H2S04 S0aH S0---- 3H o-Toluenesulfonic acid acid p-Toluenesulfonic acid Benzenesulfonic acid when further sulfonated gives m-ben- S03H zenedisulfonic acid: SULFONIC ACIDS 217 Properties. With alcohol, the sulfonic acids form esters; e.g., O-S03aH + C2H5OH -- C2H5 + H20 Ethyl benzenesulfonate (an ester) The corresponding chloride is obtained with PC15; e.g., SO PC15 -SO \OH - 1 + POCl3 + HC1 Benzenesulfonyl chloride and with NaOH we form the sodium salt; e.g., Sodium benzenesulfonate With stearn under pressure, they are decomposed, yielding the hydrocarbon, e.g., Q-S3aH + H20O + H2S04 and with hydrogen are reduced to thiophenol; e.g., SH -SOaH + 3H2 -> - 3H20 Thiophenol When fused with NaOH, the sulfonic acids yield the sodium salts of the phenols; e.g., S03Na K ONa S2NaOH - 4 Sodium phenolate + Na2SO3 + H2 0 VALENCE AND STRUCTURE IN INORGANIC CHEMISTRY 11 as the " empirical " or " simplest " formula; but this may not necessarily prove to be the " true " or " molecular " formula. For example, a quantitative analysis of acetylene and benzene would yield the same " empirical " formulas for both, namely, CH; yet acetylene is written C2H2 and benzene C6H6. In order to arrive at the actual or " molecular " formula, whether C212. or C6H6, we must further proceed to a molecular weight deter- mination, based on vapor density, or boiling-point, or freezing- point, etc. Here again the reader is referred to laboratory man- uals or to books on physical chemistry for further details.' Valence and Structure in Inorganic Chemistry.-Our studies in inorganic chemistry have led us to define valence as the number of atoms of hydrogen with which one atom of an element combines or replaces. To show such relationships graphically in any com- pound, we indicate valencies by lines or " bonds," each line repre- senting one valency. Thus: H /Cl Cl H-C, H-O-H, N C1 I C1 H \Cl Cl where not only are hydrogen, oxygen, nitrogen, carbon and phos- phorus shown to be mono-, di-, tri-,tetra- and pentavalent elements, respectively, but these valencies are indicated by bonds, each bond representing one valency. In organic chemistry, the use of graphic formulas is very extensive indeed, for only by some such method can the dis- tinguishing features of a compound be brought out at a glance. The difficulties that confront us may be seen from the following example, which has already been touched upon once before. HN03 is the formula for nitric acid and for this compound alone, but C2HO 60stands for grain alcohol or methyl ether, and C4Ho1 may represent two different compounds. Although the molecular formulas are the same, the physical and chemical properties are more or less different. We say that in these cases the different compounds are due to differences in the internal structure of the 1 Findlay, Practical Physical Chemistry; Getman, Laboratory Exercises in Physical Chemistry; Gray, Manual of Practical Physical Chemistry. 2:8 HALOGEN DERIVATIVES, SULFONIC ACIDS from which the phenol, 0--O, can be obtained by treating the solution with CO2. (This is an extremely important commercial method used in the preparation of phenol and phenolic compounds. The sulfonic acid is first made from the hydrocarbon, then the former is fused with NaOH, and the resulting compound acidified.) The sulfonic acids (salts) can be distilled with NaCN yielding the corresponding cyanides; e.g., SO3Na CN NaCN -- - + Na2SO3 The free sulfonic acids are usually very soluble in water. In order to separate them from the excess of H2S04, the Pb, Ca or Ba salts are usually prepared. The Pb, Ba and Ca sulfonates are soluble in water while the sulfates are insoluble. (For sul- fonation, concentrated H2S04 at elevated temperature must be used. Very often it is necessary to resort to fuming H2S04.) (Quite often organic compounds insoluble in water are sulfonated, converting them to water-soluble sulfonic acids. This is a procedure extensively used in the dye industry.) NITRO COMPOUNDS These are a very important class of organic compounds. They are generally prepared by direct nitration with HN03. In some instances the nitration proceeds readily, in others it does not. In some cases dilute nitric acid can be used (provided no oxida- tion takes place); in others the nitration will proceed only with concentrated or fuming nitric acid. In most cases the presence of sulfuric acid is necessary to absorb the water just as fast as it is formed in the reaction. Sometimes only fuming sulfuric acid will serve the purpose. In reality, a number of factors play their part in nitration-such as strength of nitrating acid (" mixed acid "-HNO3 + H2S04), amount of acid used, tem- perature of the reaction, length of time of nitration, agitation of the liquids, etc. NITRO COMPOUNDS Preparation. NO2 0 CH3 ro + H (H2S04) (H2S04) + HON02 --- + HONO2 Nitrobenzene CH3 CH3 (H2S04) -NO2 ON02 - + N02 p-Nitro- o-Nitro- toluene toluene + HON02(+H2S04) CH3 --N02 HON02 C + (H2S04) N02 2, 4-Dinitrotoluene NH2 (T.N.A., tetranitroaniline, 02N- / NO2 Y-NO2 NO2 and tetryl, CHa NK N NO02 02N N , or, 2, 4, 6-Trinitrophenyl methyl nitroamine NO2 are the most important high explosives.) 219 NO2 -NO2 i-Dinitrobenzene CH3 2N-^-NO2 NO2 2, 4, 6-Trinitrotoluene or T.N.T. '220 HALOGEN DERIVATIVES, SULFONIC ACIDS Properties.-The nitro compounds are usually pale yellowish liquids or solids, many of them being volatile with steam. Some of them-the higher nitro compounds, such as T.N.T.-are high explosives. NO2 Nitrobenzene.- , sometimes called "oil of mirbane," is a yellowish oil possessing the odor of bitter almonds, and is sometimes used in place of the latter in perfumes. It is also used in soaps, polishes and grease (due to its odor). It is manufactured from benzene on a very large scale for the purpose of preparing aniline, which is an important "dye intermediate," NH2 / N02 H + 2H20 H2 Aniline or H2 phenylamine Reduction products of nitro compounds under varying condi- tions: -NH2 Dimolecular Reduction Products: NO2 02N- + 311 j + Q0. 2 - NH2 Aniline N-' +112 nzene H-N-N- Hydrazobenzene READING REFERENCES 221 READING REFERENCES TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), chap. 26 (Explosives). SLossoN-Creative Chemistry. (1920), chap. 2 (Preserver and Destroyer of Life); chap. 12 (Fighting with Fumes). PHILLIP-Romance of Modern Chemistry. (1910), chap. 15 (Explo- sives). FRIES AND WEsT--Chemical Warfare. AULD-Gas and Flame. HARRow-Contemporary Science. (1921), pp. 61-75 (Methods of Gas Warfare-by Auld). YERKEs-The New World of Science. (1920), chap. 9 (The Production of Explosives). MARSHALL-Explosives. SMITH-T.N.T. and other Nitrotoluenes. ROGERS-Manual of Industrial Chemistry. (1921), pp. 1070-1091 (Explosives). GROGGINs-Aniline and Its Derivatives. (1924), chap. 7 (Nitrobenzene). CHAPTER XXIII AROMATIC AMINES,1 DIAZO AND AZO COMPOUNDS AROMATIC AMINES THE NH2 group may be attached to the nucleus or to the side- chain; e.g., NH2 CH2 - NH2 Aminobenzene or phenylamine or aniline Benzylamine As might be anticipated, the benzylamine shows the general properties of an aliphatic amine, since the NH2 group is in the side-chain. The aromatic amines, like those of the aliphatic series (p. 132), may be either primary, secondary or tertiary; e.g., H NCH3 N7 N CH C3 CH3 CH2-C Monomethylaniline Dimethylaniline Benzylphenylamine or methylphenylamine or dimethylphenylamine oHo Diphenylamine Triphenylamine 1 The student should review Chapter XIII on aliphatic amines. AROMATIC AMINES The aliphatic amines are stronger bases than the corresponding aromatic amines. The primary, secondary and tertiary amines form salts such as /CHa -N-CH3 Dimethyl phenyl ammonium chloride or Dimethylaniline hydrochloride but if all the groups attached to the nitrogen atom are aryl,' then no salts are formed. Triphenylamine, for example, does not form a salt with hydrochloric acid. Preparation.-The amines are generally prepared by reducing the nitro compounds; e.g., N 02 H2 NH2 + H2 - + 2H20 H2 (It may be remembered that the aliphatic amines can be prepared by the action of ammonia on the halogen compound: CH3C1l + HINH2 -- CH3NH2; but chlorobenzene, -Cl, does not react with ammonia under analogous conditions.) Reactions with Nitrous Acid.-The aliphatic primary amines yield alcohol when treated with nitrous acid; e.g., CH3 NH2 + HONO --- CH30H + N2 + H20 but with the aromatic primary amines, the reaction is quite different; e.g., 0-NH2 + HC1 1The "aryl" (Ar) groups refer to C6H5 and its homologues, just as the "alkyl" (R) groups refer to the aliphatic groups. 223 224 AROMATIC AMINES, DIAZO AND AZO COMPOUNDS N=N N. . HO Cl \H 0 // i Cl (NaN02 + 2HC at low temperature) Aniline hydrochloride Benzene diazonium chloride (This reaction-the "diazo reaction "-will be taken up later on p. 229.) * The secondary amines of the aliphatic series, it will be recalled, yield nitroso compounds; e.g., (CH3)2N--IH + HO NO - (CH3)2=N-NO + H20 Nitrosodimethylamine and so do the aromatic amines; e.g., ( CH - } CH 3 + 120 H + HOINO NO Nitrosomethylaniline The tertiary amines of the aliphatic series-e.g., (CH3)3N, do not react with HONO, but those of the aromatic series do. (There are a few exceptions which need not be discussed here); e.g., CH3 CH3 N CH3 NCH3 + H20 IH + HO NO NO p-Nitrosodimethylaniline Very many amines are known, and many are used in the industries. A few of them will be mentioned. NH2 Aniline, , or phenylamine, or aminobenzene, was AROMATIC AMINES first produced by the distillation of indigo. (The Portuguese word for indigo is "anil," hence the name "aniline.") It occurs in small quantities in coal tar and bone oil. On an industrial scale, it is manufactured from nitrobenzene: -NO2 -NH2 + 312 + 220 (Fe + HCI) Aniline, when freshly distilled, is a colorless oil, which darkens on standing; b. p. 184.40. It is the basic substance from which hundreds of dye intermediates are manufactured. (The first synthetic coal tar dye, "mauve," was made on a commercial scale by Perkin, who used aniline as his starting material.) Aniline is poisonous, producing vertigo, weakness and cyanosis. An aqueous solution of it, when mixed with bleaching powder, gives a violet color; with potassium dichromate, a blue color is obtained. Being a base, aniline forms salts with acids, such as S -NH2 HC1 Aniline hydrochloride With bromine, aniline forms 2, 4, 6 (sym)-tribromoaniline NH2 Br- -Br and with nitrous acid, we get a diazonium com- Br pound ("diazo reaction," see p. 229). NH - OC - CH3 Acetanilide, or acetyl aniline (also called "antifebrin,") is formed when aniline is acted upon by glacial acetic acid or acetic anhydride. It is used in medicine as an analgesic and antipyretic, and is used in neuralgia, rheumatism and in headache 225 226 AROMATIC AMINES, DIAZO AND AZO COMPOUNDS powders. When aniline is heated with H2S04, sulfanilic acid is produced: NH2 NH2 + cone. H284- H20 S03H Sulfanilic acid Aniline reacts with carbon disulfide, CS2, to form /NH-~) C=S + H2S \NH-/J Thiocarbanilide which is used as an "accelerator " in the vulcanization of rubber. (By an "accelerator " we mean a substance which "hastens " the reaction between the sulfur and the rubber.) It also has an effect on the physical properties of the vulcanized rubber, in that it increases the tensile strength. Besides thiocarbanilide, the following are the more important accelerators: hexamethylene- tetramine (p. 74); diphenylguanidine, H C=-NH H> N and triphenylguanidine, H N &=-K AROMATIC AMINES The toluidines or aminotoluenes, CH3 CH3 o-Toluidine or o-aminotoluene m-Toluidine CH3 NH2 p-Toluidine Of the three toluidines, the o- and p- may be obtained by the reduction of the corresponding nitro compounds. A few other amines are NH2 0 CH3 H3 m-Xylidine or 1, 2, 4-xylidine CH3 Methylaniline N/CH3 / \CH3 Dimethylaniline The last two are manufactured by heating aniline and methanol under pressure, the one or the other amine being obtained, depend- ing upon the ratio of the reacting substances used. Both the methylaniline and the dimethylaniline are used extensively in the manufacture of dye intermediates and dyes. Nitrous acid reacts with dimethylaniline as follows: N(CH3)2 in KCN + CuCN --> OBr N N CN /+ N2 CN 3 O + N,, O C N N b=- CI" 232 AROMATIC AMINES, DIAZO AND AZO COMPOUNDS We may summarize these reactions to show the preparation of various types of aromatic compounds: H OR C1 Br (orO CONH2 or OOR COO Metal which gives an idea of the wide applicability which these dia- zonium compounds possess. We must now proceed to reactions which are better explained DIAZO AND AZO COMPOUNDS N=N--Cl by the structure U . Upon partial reduction, the following reaction takes place: H H -Cl I I N-N . HC + 4H -I Phenylhydrazine hydrochloride -N-NH2 and the base, phenylhydrazine, H , may be obtained by the addition of NaOH. (Hydrazine is H2N-NH2.) Phenylhydrazine, a poisonous liquid, has been used very extensively by Fischer and others in determining the structure of sugars. It is used in the identification of sugars (p. 163), in tests for aldehydes and ketones (p. 73), in the manufacture of antipyrine (p. 311) and various dyestuffs. Diazobenzene chloride may be " coupled " with aniline (in neutral or weak acid solution) thus: H /H N=N- Cl + H -N N= N-N H Diazoaminobenzene and with dimethylaniline: O OC. CH3 Phenyl acetate OH + HCI OH OH OH OH OH OH 3 -N02 + dil. HN03 --> NO2 + p-Nitrophenol o-Nitrophenol + H2S04 OH -j S03H p-phenolsulfonic acid OH o-Phenolsulfonic acid Zn dust + ZnO +distilled-- Zn + POC13 -- O Na + I CH3 o/~C O-P---O-- + 3HC1 Triphenylphosphate (a camphor substitute) OCH8 Methyl phenyl ether or anisole or methoxybenzene OH PHENOLS Phenol gives a violet coloration with ferric chloride. It is a colorless, crystalline substance which becomes liquid upon the addition of 15 per cent of water. It is a powerful antiseptic, disinfectant and germicide, and is used to a certain extent (in 3 per cent solutions) as a dressing for wounds, for disinfecting surgical instruments, rooms, etc. Phenol is also used in the manufacture of explosives, dyes, developers, various medicinals, bakelite and other resins, etc. The resins, of which " bakelite " is an example, are suffi- ciently important to warrant a few words of description. Phenol combines with formaldehyde to produce a resinous material. These products-known as bakelite, redmanol, etc.-vary in properties, for the particular type of resin obtained will depend upon the exact method employed in its preparation. Pure phenol and pure formaldehyde react very slowly, even when heated, but in the presence of catalytic agents, particularly bases- ammonia seems to be used in many cases-the action is accel- erated. Where ammonia is used, it is believed that what first takes place is a reaction between the formaldehyde and the ammonia, forming hexamethylenetetramine (p. 74), and that the latter then combines with phenol, forming a resin, the chemical composition of which is not clear. This resin undergoes further changes when heated. It then becomes less fusible and less soluble. The raw bakelite, for example, is both soluble and fusible, but when heated becomes insoluble, infusible, very hard, strong and resistant. This bakelite is used in moulding materials, varnishes, enamels, lacquers, cements, pipe stems, cigar holders, handles, insulating substances, etc. Cresols. CH3 CH3 CH3 -OH o-Hydroxytoluene or o-cresol m-Cresol OH p-Cresol All three are present in coal tar and in wood tar, and all three act as antiseptics. They are known as " cresylic acid " or "tri-cresol." The properties of these cresols are, in general, 239 LEO HENDRIK BAEKELAND (1863- ) PRESENT (1924) PRESIDENT OF THE AMERICAN CHEMICAL SOCIETY AND HONOR- ARY PROFESSOR OF CHEMICAL ENGINEERING AT COLUMBIA UNIVERSITY, IS BEST KNOWN FOR HIS WORK ON "BAKELITE" (P. 239), SYNTHETIC PLASTICS IN GENERAL AND FOR "VELOX" (THE PHOTOGRAPHIC PAPER). 240 PHENOLS similar to phenol. The cresols have greater germicidal power than phenol and are less poisonous. They are slightly soluble in water and are rendered more soluble by the addition of soap. Preparations such as lysol, creolin, phenoco, etc., contain cresols. Cresols are also used for the manufacture of synthetic resins, dyestuffs, explosives and organic chemicals. CH3 Thymol, , or 3-hydroxy-1-methyl-4-isopropyl- -OH benzene, CH CH3 CH3 occurs in oil of thyme, mint. and other essential oils, and is an important antiseptic. It is very often used in the treatment of hookworm and to preserve urine. Diiododithymol (prepared from thymol and iodine) is known as "aristol" and has largely displaced iodoform as an antiseptic. OH o-Dihydroxybenzene, , or pyrocatechol, occurs in "catechu " resin and is prepared from resins by fusing them with KOH, or from o-phenolsulfonic acid; OH OH -SO3H KOH -OH fusion etc. It is used in the manufacture of adrenaline and guaiacol. Resorcinol, or m-dihydroxybenzene, or resorcin, is prepared thus: S03H OH NaOH j-S03 fusion -OH etc. m-Benzenedisulfonic acid Resorcinol .241 242 AROMATIC ALCOHOLS, PHENOLS AND ETHERS It is used as an antiseptic and an antipyretic, and in the prepa- ration of dyestuffs. Quinol, or p-dihydroxybenzene, or hydroquinone, is prepared from p-benzoquinone (p. 250) by reduction: 0 OH + H2 O OH It is used as a photographic developer (that is, as a mild reducing agent, it being converted into benzoquinone). Of the three trihydroxybenzenes, pyrogallol (or pyrogallic acid) is obtained by heating gallic acid: OH OH HO OH HO- -OH - J + C02 Pyrogallol COOH It is a strong reducing agent and absorbs oxygen in alkaline solution-a property used in estimating oxygen in gas mixtures. Pyrogallol is also used as a photographic developer and in the manufacture of dyestuffs. Phloroglucinol, or sym. (1, 3, 5)-trihydroxybenzene, may be prepared from the corresponding sulfonic acid: HOS- -SO3H NaOH HO- -OH fusion etc. Q SO3H OH sym-Benzenetrisulfonic acid Phloroglucinol It occurs in the glucoside phloridzin and in different resins. (The behavior of phloroglucinol towards reagents is worthy of discussion. That it is a trihydroxy compound is shown by the fact that it forms a triacetyl derivative with acetic anhydride. ETHERS On the other hand, it forms a trioxime with hydroxylamine, indicating a ketonic structure-compare p. 129: 0 I I /C H2=C C=H2 \c/ II H2 where, under certain conditions, the same compound may exist in two different forms, we have a case of tautomerism. This is to be distinguished from isomerism, where we have two different compounds having the same molecular formula.) Phloroglucinol is used for the determination of furfural (p. 310)-a test based upon the production of a red color. ETHERS 1 OCH3 Methyl phenyl ether or anisole or methoxybenzene OC2H5 0 Ethyl phenyl ether or phenetole or ethoxybenzene 0 Phenyl ether or phenyl oxide Ethers of the type of anisole and phenetole are produced thus: OINa + IJCH3 OCH3 Sodium phenolate ONa / OC2H5 + (C2H5)2S04 -> + C2H5NaSO4 Diethyl sulfate 1 The student is advised to review Chap. VI, p. 64. 243 244 AROMATIC ALCOHOLS, PHENOLS AND ETHERS The phenyl ether is prepared by heating phenol with zinc chloride: OH1-H H 1 - 0 + H20 It has a geranium-like odor. These ethers are used in synthetic perfumes. READING REFERENCES SLossoN-Creative Chemistry. (1920), chap. 7 (Synthetic Plastics). ELLIs--Synthetic Resins. HARROW-Contemporary Science. (1921), pp. 152-191 (Before and After Lister). [Use of Phenol]. CHAPTER XXV AROMATIC ALDEHYDES,' KETONES AND QUINONES O THE aromatic aldehydes and ketones contain the -C/ H and >C=0O groups, respectively (like the aliphatic compounds). The quinones have no analogues in'the aliphatic series. AROMATIC ALDEHYDES The most important aromatic aldehyde is CHO Benzaldehyde, , or phenyl formaldehyde, or benzoic aldehyde, or artificial oil of bitter almonds. This compound may be prepared in several ways: CH3 CHCl2 2C12 (hot; sunlight; no carrier) Toluene Benzal chloride CH3 / H20 Ca(OH)2 under pressure CHO 0 CHO / partial oxid. MnO2 1 The student should review Chap. VII, p. 67, on the aliphatic alde- hydes and ketones. 246 AROMATIC ALDEHYDES, KETONES AND QUINONES Benzaldehyde occurs in bitter almonds, the kernels of fruits, etc. In bitter almonds, the aldehyde is present in the form of a glucoside (amygdalin). An enzyme (p. 339) present in amygdalin and known as " emulsin," hydrolyzes the glucoside into glucose (hence the name " glucoside "), hydrogen cyanide and benzalde- hyde. (This hydrolysis may also be brought about by means of acids.) Benzaldehyde is used extensively in flavoring extracts, perfumes, the manufacture of dyes, and in the preparation of various organic compounds. Properties.-Many of the properties of benzaldehyde resemble those of the aliphatic aldehydes. When exposed to air, it is COOH oxidized to the corresponding benzoic acid, ; it reduces ammoniacal silver nitrate solution; it forms addition compounds with NaHS03 and HCN; and reacts with hydroxylamine and phenylhydrazine to form oximes and hydrazones, respectively. With ammonia, sulfuric and nitric acids, and with chlorine, the following reactions take place: CHO CH 3 + 2NH3 ( 3 N2 + 3H20 Hydrobenzamide CHO CHO + H2S04 - + H20 0-S03H m-Sulfobenzaldehyde CHO CHO + HN0-Nrob3 enze+ Hye m-Nitrobenzaldehyde AROMATIC ALDEHYDES COC1 CHO + C12 + HC1 Benzoyl chloride The reaction with hydroxylamine is as follows: CH O + H2jNOH 0 CH=NOH enzldoxim20 Benzaldoxime Two forms-stereoisomeric forms-p. 88, are known: C-H C-H QN-OH HO-N Syn-Benzaldoxime (m.p. 1250) Anti-Benzaldoxime (m.p. 350) Other reactions for benzaldehyde will be given in subsequent chapters (pp. 257, 299). CH2 - CHO Phenyl acetaldehyde, , has a hyacinth odor and is used in perfumes. Cinnamaldehyde, CH=CH-CHO 0 , or P-phenyl acryl- aldehyde, is the chief constituent of oil of cinnamon, and is used in perfumery. It can be synthesized by condensing benzalde- hyde with acetaldehyde: -CH, H2 CH CHO NaOH sol -CH=CH-CHO %~C~ + 2NOslQ 247 INTRODUCTION It must not be supposed that when we write methane, H I H-C-H, we have any intention of fixing the atoms in space. H In any case-and this has already been referred to-two-dimen- sional configurations cannot truly represent the structure of any form of matter. But we do wish to emphasize that in the formula for methane the four hydrogen atoms are to be regarded as of equal value, so that when a hydrogen atom is replaced by a chlorine atom, it does not matter whether we write C1 H H H H-C-H or Cl-C-- or H-C-H or IH-C--C H H Cl H for they all represent one and the same compound, namely, mono- chloromethane; nor, if two hydrogen atoms are replaced by two chlorine atoms, does it matter whether we write Cl C1 C1-C--H or H-C-H H C1 for both represent the same compound, dichloromethane. The Electron Conception of Valence.-Based on modern work on the structure of the atom, many chemists have been busy recently developing ideas of valency in accord with the electronic conceptions of matter. As early as 1907 J. J. Thomson stated that for each valency bond established between two atoms, the trans- ference of one-negatively charged-corpuscle (electron) from one atom to the other has taken place, the atom receiving the cor- puscle (electron) acquiring a unit negative charge, while the atom losing the electron acquires a unit positive charge. Thus, a neu- tral H atom and a neutral C1 atom would become positively and 248 AROMATIC ALDEHYDES, KETONES AND QUINONES AROMATIC KETONES The aromatic ketones are divided into those containing aryl 0-CO OCH3 and alkyl groups; e.g., and those in which both the groups are "aryl "; e.g., -CO- CO - CH3 Acetophenone, , or methyl phenyl ketone, or "hypnone," is used as a soporific. It may be prepared by heating a mixture of CO . CH3 COOcal + ca'OOC.CH3 c Calcium acetate --- + CaCO3 Calcium benzoate or H + Cl1OC.CH3 (AICl3) CO-CH3 Acetyl chloride ----- + HC1 The last is an application of the Friedel-Craft's reaction. Benzophenone, 10 , or diphenylketone, may be prepared by an application of the Friedel-Craft's reaction: -COJ Cl + H 0 (AI13) -co- -~ U+ HCI Benzoyl chloride 1ca here indicates Ca. AROMATIC KETONES or by the distillation of calcium benzoate: CCa C Ca + CaCO3 cOo or by the oxidation of diphenylmethane: -CH2 0 xid. Benzophenone, when reduced, forms benzohydrol, or diphenyl- carbinol: -C OH (Michler's ketone, or p, p'-tetramethyldiaminodiphenyl ketone, is manufactured as follows: Cl H-- -N(CH3) /N(CH)2 C=O + - C=O \Cl H <-->N(CH( I --N(CH3)2 Phosgene It is an important dye intermediate.) Benzoin, \OH ,is obtained from benzalde- hyde when treated with alcoholic KCN solution, two molecules of the former condensing (aldol condensation type, p. 76). 249 250 AROMATIC ALDEHYDES, KETONES AND QUINONES QUINONES The CO group in an aromatic Quinones are aromatic compounds ring; e.g., 0 Ij O 0 ketone is not part of the ring. in which the CO is part of the CO.CH3 0A ketone A ketone A quinone (When the 2 CO groups are in the p-position with respect to one another, we get p-quinones, and when in the o-position, o-quinones. No m-quinones are known.) The quinones may be regarded as derivatives of dihydro- benzenes in which 2(CH2) groups are replaced by 2(CO) groups: CH2 HC CH HCO CH CH2 O /c Quinone, C 0 /C oxidation of hydroquinone: CH2 HC CH2 HC /CH CH O 0 ii , or benzoquinone, may be prepared by the OH 0 Oxid. OH O or by the oxida- QUINONES tion of aniline with Na2Cr207 + H2S04; or, by oxidizing amino and hydroxy compounds belonging to the p-series; such as NH2 0 SO3H p-Aminobenzenesulfonic acid NH2 NH2, etc. OH p-Aminophenol Benzoquinone is a yellow, crystalline solid, volatile with steam and possessing a pungent odor. It is reduced to hydroquinone; 0 H2 (SO2 + H20O OH OH forms mono- and di- oximes: O+H2 NOH N-OH I I 0 0 + H2 INOH Benzoquinone monoxime and halogen derivatives; e.g., + Br2 (in CHC13 0 H H-C C
C C
CHO 1The student should review Chaps. VIII, IX XI, and XII. 253 254 AROMATIC ACIDS AND THEIR DERIVATIVES or by the hydrolysis of benzotrichloride: //C C13 H OH 0C-0 COOH C +OH OH H OH or by the hydrolysis of the corresponding cyanide: CN COOH / / 0o-0 Benzonitrile or cyanobenzene or by the application of the Friedel-Craft's reaction: COOH H + Cl -C-Cl CO Cl + H OH O (AICls) Phosgene Benzoyl chloride Benzoic acid occurs (as the free acid or as the ester) in gum benzoin, resins, balsams of Tolu and Peru, berries, etc. The free acid is generally purified by sublimation. Its properties are similar to those of compounds containing, on the one hand, a benzene nucleus, and on the other hand, a carboxyl group. Some of its reactions may be summarized as follows: + NaOH ------ COONa+ H20 Sodium benzoate (used as a food preservative) COOC2H5 C00 OH + H 10C2H5 H2SO4 Ethyl benzoate (used in artificial flavors and in perfumery) BENZOIC ACID + POC13 + HC1 :COOH + PC15 jCOCl Benzoyl chloride O COI+ NaJC 1 + NaC1 Benzoic anhydride (Heat) -O (Hea) 0C 0 + CaC03 Benzophenone CONH2 qCO C1 + HJNH20 Benzamide COOH 0 + HNO3 -H20 (P205) Benzonitrile COOH NO2 m-Nitrobenzoic acid COOH, SO3 H m-Sulfobenzoic acid CN ~{svo I 255 256 AROMATIC ACIDS AND THEIR DERIVATIVES 0-CO C1 + H OC2H5 COOC2H6 (with NaOH) -' + NaCl + H20 Ethyl benzoate Benzoic acid itself finds use in medicine as an antiseptic and also in the manufacture of dyes. Sodium, lithium and ammonium benzoates are used as internal antiseptics. Sodium benzoate is used as a food preservative. An interesting synthesis of hippuric acid in the body-by the kidneys-is brought about by the combination of benzoic acid (obtained from fruits, vegetables and, to some extent, pro- teins) and the amino acid, glycine, (obtained from the decomposi- tion of proteins): -CO OH H NH -CONH-CH2- COOH CH2 - COOH The toluic acids, CH3 liippuric acid or benzoylglycine CH3 0- M/- CHa COOH p- can be prepared by partial oxidation of the corresponding xylenes, or from the corresponding toluidines. --CH2CO00H Phenylacetic acid, K , has its carboxyl group in the side-chain and is isomeric with the toluic acids. It may be prepared from benzyl chloride- -CH2 Cl + KJCN CH2* CN Hydrolysis CH2C00OH Benzyl cyanide HYDROCINNAMIC ACID The acid and its esters are used in perfumery. Cinnamic acid, I-CH=CHCOOH , or 0-phenylacrylic acid, may be prepared by Perkin's reaction: -CH O + H2 CH.COONa I -CH=CHCOONa In presence of acetic anhydride (dehydrating agent) Sodium cinnamate + acid/ -+ CHC--HCOOH Esters of cinnamic acid and the acid itself are present in oil of cinnamon, resins, storax, balsams, gums, etc. The esters are used in flavoring materials and perfumery. The properties of cinnamic acid are those of a compound containing (a) a benzene nucleus, (b) a double bond structure, (c) a COOH group. Hydrocinnamic acid, 0-CH2-CH2C00H propionic acid, is prepared from cinnamic (sodium amalgam and water). Of the phthalic acids, COOH Phthalic acid COOH -COOH Isophthalic acid acid or 0-phenyl- by reduction COOH I COOH Terephthalic acid the first, or phthalic acid, is the most important. It may be prepared by oxidizing o-xylene: 257 THE ELECTRON CONCEPTION OF VALENCE negatively charged, respectively, should the H atom lose an elec- tron to the Cl atom: H -O H+ Cl +O Cl- H++Cl- - HCl An atom is capable of losing or gaining as many electrons as it has valencies and may function either as a positively or negatively charged atom. (Most elements have a greater tendency to behave one way than another.) If the Cl atom loses an elec- tron, it becomes positively charged; e.g., hypochlorous acid, + -- + C1 0 H; but if it gains an electron, it becomes negatively charged; +- e.g., H Cl. A divalent atom may function in three ways: through the gain of two electrons; through the loss of two electrons; and through the simultaneous loss of one electron and gain of another; e.g., S++ +- 0 0 0 With a trivalent element there are four possibilities: N: N, NT N1 An atom, then, whose valence is n may function electronically in n+ 1 different ways. If this conception be applied to carbon, we might expect the carbon atom, with its tetravalency, to function in five different ways: ---+- --++ -+++ ++++ C C C C C Applying the electronic conception of valence to a few simple carbon compounds-to methane, methanol (wood alcohol), for- maldehyde, formic acid and carbon dioxide-we get the fol- lowing: 258 AROMATIC ACIDS AND THEIR DERIVATIVES CH3 COOH Oxid. 0 -CH3 o 0 -COOH _CH (HNO3 or KMn04) The commercial method is to pass the vapor of naphthalene and air over vanadium pentoxide (V205) (or other catalysts) at about 4000: Oxi d. o 120 -COOH O COOH Phthalic anhydride Some of the reactions of phthalic acid may be summarized: COOH Heat -CO INH COH -COOH -CO CO Phthalic anhydride Phthalimide />-COO H HO C2H5 -COOC2H5 -COO H HO C2H5 )-CO0C2H5 Diethyl phthalate (The diethyl phthalate is a bitter substance and is used as a denaturant for ethyl alcohol.) Z/Cl 0-CO + PC1, -C Phthalyl chloride C O CO ~ -O H alkalies I acids 1o + H H OH OH Phenolphthalein (colorless) HYDROCINNAMIC ACID --0 ONa (pink) Phenolphthalein is one of the best-known indicators. It is also used as a purgative. Phthalic anhydride is used in the manufacture of anthraquinone (p. 286), and in the manufacture of several important dyes. OH OH Phenolsulfonephthalein, phthalein, and phenoltetrachloro- OH OH C / C , are used to test the functional activities C1 Cl of the kidney and liver respectively. 25.9 260 AROMATIC ACIDS AND THEIR DERIVATIVES COOH HOOC-- COOH Mellitic acid, , or benzene hexacar- HOOC- --COOH COOH boxylic acid, may be prepared by the oxidation of graphite with HNO3. Its aluminium salt occurs in nature as the mineral "honey stone." When heated with soda lime, the acid is con- verted into benzene: COOH HOOC-/ -COOH -6C02 HOOC- -COOH COOH READING REFERENCES SHERWIN-The Fate of Foreign Organic Compounds-Benzoic acid, etc. -in the Body. Physiological Reviews, 2, 238 (1922). ANoN.-Influence of Sodium Benzoate on Nutrition and Health of Man. (Agricultural Dept. Report 88.) Government Printing Office, Washington. CHAPTER XXVII ADDITIONAL AROMATIC COMPOUNDS CONTAINING MIXED GROUPS 1 So far we have largely considered compounds containing single groups attached to the benzene ring, such as nitro com- pounds,. sulfonic acids, phenols, aldehydes, etc.; and also, to some extent, a number of compounds containing dissimilar or mixed groups. In this chapter we shall consider additional compounds with unlike or mixed groups attached to the benzene ring. As thousands of such substances are known, only a few of the common and important ones can be mentioned. (Note to student: In studying the following compounds, the student should bear in mind that each group attached to the ring is responsible for certain characteristic reactions, and that the properties of the compound as a whole are, as a rule, the summation of properties exhibited by the individual groups present. For example, such a compound as OH -OCH3 CHO shows properties due (a) to the presence of the benzene ring, (b) to the OH group, (c) to the OCH3 group and (d) to the CHO group.) 1 The student is advised at this point to review the rules for substitution in the benzene ring (p. 203). ADDITIONAL AROMATIC COMPOUNDS Chlorotoluenes, or tolyl chlorides.-Three isomers are known: CH3 CH3 Cl CH3 0-C A mixture of the first two (o- and p-) is obtained when toluene is chlorinated (in presence of a halogen carrier). Direct chlori- nation of toluene does not yield the third, or m- variety; but we CH3 may start with m-toluidine, , diazotize it, and apply --NH2 the Sandmeyer reaction (p. 231). Three isomeric chloroanilines are known. When aniline is NH2 cl-Z -ci treated with chlorine, sym.-trichloroaniline, ,is ob- Cl tained. Of the three nitroanilines NO2 NO2 NO2 NH2 the second (m-variety) is prepared by treating benzene with nitric and sulfuric acids to produce the m-dinitrobenzene, and then employing a sufficiently mild reducing agent to reduce but one of the NO2 groups: 262 CHLOROTOLUENES NO2 3H2S j NH2+ 2H20 + The p-nitroaniline is obtained as follows: NH- OC- CH3 CH3COOH 0 Acetanilide HON02 NH -OCCH3 NO2a p-Nitroacetanilide NH2 HOH NO2 p-Nitroaniline (The object of first acetylating is to "muzzle" the NH2 group; or in other words, the NH2 group must be protected against the oxidizing action of nitric acid.) The o- and p-nitrophenols are prepared by direct nitration of phenol; the m- variety is prepared from m-nitroaniline: NO2 S |DDiazotize I-NH2 (HCI + NaNO2) OH NO2 SN-N Cl N02 HOH -OH or sym.-trinitrophenol, may NO2 / 2HON02 (H2S04) 263 Picric acid, ADDITIONAL AROMATIC COMPOUNDS be prepared from phenol by nitration. Commercially, it is manu- factured thus: OH OH H2S04 3HN03 S03H p-Phenolsulfonic acid OH 0sN- -NO2 + H2S04 + 2H20 NO2 Picric acid is more strongly acidic than phenol, the increased acidity being due to the presence of the nitro groups. It is used in a colorimetric method for determining glucose in the blood, as a test for creatinine, as a precipitant for organic bases and proteins, as a "fixing" agent in histological work, in the treat- ment of the skin diseases and of burns, as an antiseptic, and in the manufacture of explosives. Picric acid is also used for the OH 02N- -NH2 preparation of picramic acid, and sodium pi- NO2 cramate, which in turn are converted into several green and brown dyes. (Many of the nitro compounds of the aromatic series, such as picric acid and T.N.T.-p. 219-are powerful explosives. They were .used extensively during the late war.) NH2 Sulfanilic acid, , or p-aminobenzenesulfonic acid, is SO3H 264 SULFANILIC ACID prepared from aniline by treatment with sulfuric acid, which first NH2 H2S04 forms aniline acid sulfate, 6 , and this on heating to 1800 is converted to sulfanilic acid. The acid is used in the manufacture of several dyes. (Since this compound contains a basic-NH2- and an acidic-S0aH-group, an "inner salt," of the type N-H H H O S 0 O is possible. NH2 Compare with amino acids, p. 138.) is metanilic acid. It is prepared by reducing m-nitrobenzenesulfonic acid and is used in the preparation of azo dyes. Of the phenolsulfonic acids, OH OH OH -SO3H3H 0- m- S03H the o-variety is prepared by treating phenol with H2S04 (in the cold), the p-, by heating phenol' with H2S04 to 960, and the m-, by cautiously fusing (with NaOH) the m-benzenedisulfonic acid. 265 ADDITIONAL AROMATIC COMPOUNDS A mixture of the o- and p- is used as an antiseptic under the name " aseptol." CH3 The o-Toluenes-SO3H The o-Toluenesulfonic acid, , is used in the preparation of saccharin (p. 275). CH3 Chloramine-T, r , orsodium-p-toluenesulfon-N-chloramide OCl or "ch,orazene " (a derivative of p-toluenesulfonic acid), is used as an irrigating fluid in the treatment of wounds, as a mouth wash, and, in general, as an active germicide. (It has approximately four times the antiseptic value of phenol.) It was introduced by Carrel and Dakin during the late war. CH3 Dichloramine-T, i , or p-toluenesulfon-N-dichloramide, is SO2 NC12 also used in the treatment of infected wounds. OH -OCH, Guaiacol, , or o-methoxyphenol, or the monomethyl ether of catechol, is found in gum guaiacum and in beechwood tar, and is obtained from guaiac resin by distillation. (The guaiac resin, dissolved in alcohol, is the "guaiac reagent" used in tests for oxidizing enzymes, blood, milk, etc.) Guaiacol, as well as some of its salts and esters, is used as internal antiseptic. 266 CHLOROTOLUENES CH2-CH=CH2 Eugenol, -OCH3 OH , or 4-allyl-2-methoxyphenol, is present in oil of cloves. It is an antiseptic and local anesthetic CH=CHCH3 used in dentistry. An isomer is isoeugenol, -OCH3 OH CH2-CH=CH2 , or 1-allyl-3, 4-methylenedihydroxy benzene is the chief constituent of oil of sassafras. an anodyne. CH=CHCH3 It is used a Anethole, 0 OCH3 , p-propenylanisole is found in anise seed oil and is used as an antiseptic. NH2 p-Aminophenol, OH Safrole, , is prepared as follows: 267 16 INTRODUCTION H+ H+ H+ I I I + -- + + -+ -- + -+ -- H-C-H H-C-0-H C=O -r -+ H+ H+ H+ CH4 CH40 • CH20 H+ C=0O + ++ +// Or .* -- H+ CH202 C02 (Consult the references at the end of the chapter-Falk and Nelson, Noyes and Langmuir.) Classification of Organic Compounds.-There are two main divisions, the " aliphatic " and the " aromatic." The aliphatic compounds are related to methane, CH4, and are " open chain." They get their name from the fact that animal and vegetable fats belong to this series. The aromatic (" ring " or " cyclic ") compounds are related to benzene, C6H6, and many are characterized by fragrant odors; hence the name. The line of demarcation of aliphatic and aromatic compounds is not a sharp one, for not all aliphatic compounds can be directly traced to fatty substances, nor do all aromatic compounds have odors. On the other hand, many aliphatic compounds possess very characteristic odors. Nevertheless, there are, as a rule, some general differences which help to differentiate the two great divi- sions, perhaps the most important being differences in a number of chemical properties (p. 194). ADDITIONAL AROMATIC COMPOUNDS NO2 b Reduction (Zinc dust and alcohol) NH SOH 0 Rearrangement (in presence of HCI) Phenylhydroxylamine OH NH2 and is used as a photographic developer and in the manufacture OH of such dye intermediates as p-hydroxydimethylaniline, IN /CH3 \CH3 The 1, 4, or p-aminophenol type of compouna and its derivatives make the best photographic developers. Some of the compounds used as photographic developers are: OH NH2 *HC1 Rhodinal or p-aminophenol hydrochloride OH (Q NH2 -HCl HCl Amidol or 1, 3-diamino-4-hydroxybenzene dihydrochloride 2- H2S04 NH. CH3 Metol and there are number of others. 268 PHENETIDINE OC2H5 Phenetidine, , or p-aminophenetole, is used in the NH2 preparation of phenacetin, and phenacetin is administered. OC2H5 Phenacetin, , the acet NH -OC -CH3 often appears in the urine when yl derivative of p-phenetidine, is used as an antipyretic and analgesic. OC2H5 D u lc in , 2 NH- OC-NH2 , or p-phenetole carbamide, is also called " sucrol." It is two hundred times as sweet as cane sugar. OH Salicyl alcohol, or o-hydroxybenzyl alcohol, or saligenin occurs in combination with glucose in the glucoside salicin (present in willow bark). It has been recently recom- mended as a local anesthetic. 269 ADDITIONAL AROMATIC COniPOUNDS Salicylaldehyde, OH /\-CHO prepared by the Reimer-Tiemann r ONa O0 + CHC13 + 3NaOH ,or o-hydroxybenzaldehyde, is eaction: /+ acid Na / -CHO + 3NaC1 + 3H20 (The p-modification is also produced, but the o- and p- can be separated by steam distillation, the o- passing over with the steam.) This aldehyde occurs in oil of spiroea and oil of certain flowers and is used in perfumery and in the preparation of coumarin (p. 313). OCH3 Anisaldehyde, , or p-methoxybenzaldehyde, is found CHO in anise seed oil and is used in perfumery. CHO Vanillin, , or m-methoxy-p-hydroxybenzaldehyde, OH is present in vanilla bean and is the chief constituent of extract of vanilla. It is manufactured by the oxidation of isoeugenol: 270 SALICYLIC ACID OH OH 0-OCH3 CH=CHCH3 03 ------9 or KMnO4 DH-- CH-CH3 0 --0-0 and also from guaiacol by the Reimer-Tiemann reaction (see above). It is used in perfumery, as a flavoring agent and as a gastric stimulant. OH Salicylic Acid, , or o-hydroxybenzoic acid, occurs in blossoms of meadow sweet, and, as its methyl ester in oil of wintergreen. It is prepared by the Kolbe-Schmitt reaction: ONa Heat in CO2 --O-C-ONa autoclave -- II II at 0O at 1300 11000 Sodium phenyl carbonate K-O-C-ONa OH acid -.OH -H- 0 COONa -COOH Salicylic acid is sometimes used in medicine for the treatment of rheumatic diseases, to check gastric fermentation and also as an antipyretic and intestinal antiseptic. It is most commonly administered in the form of some of its derivatives, such as salol, aspirin, sodium salicylate, strontium salicylate and methyl salicylate. It is employed to some extent in the preparation of corn cures and skin disease salves. Large quantities are used in the manufacture of dyestuffs. 271 ADDITIONAL AROMATIC COMPOUNDS OH Methyl salicylate, CH3 , is the chief constituent of "oil of wintergreen," and is the artificial oil of wintergreen. It is prepared by heating salicylic acid with methanol (esterifi- cation): OH A number of the salicylates, and their derivatives, such as OH Sodium salicylate OH 0-COOC2H5 Ethyl salicylate O- OCCH3 Phenyl salicylate or "salol" Acetyl salicylic acid, or "aspirin" ONa 0-COONa Disodium salicylate OOCCH3 0-COONa Sodium acetyl salicylate are used as intestinal antiseptics and as antipyretics. There are three isomers of nitrobenzoic acid: COOH COOH NO2 COOH -N02 272 METHYL SALICYLATE the first two being prepared from toluene; e.g., CH3 + HN03 -- CH3 b and the m-variety, by direct nitration of benzoic acid. reduction they yield the corresponding amino acids. NH2 A number of derivatives of p-aminobenzoic important local anesthetics. Anesthesine is p-aminobenzoate. Novocaine is acid, COOH NH2 are J , ethyl COOC2H5 NH2 COO CH2. CH2 . N(C2H)2 HC1. CH3 02 + NO + oxidation 1 COOH 02 b NO2 273 274 ADDITIONAL AROMATIC COMPOUNDS It is only one-seventh as toxic as cocaine. Procaine is another name for novocain. Butyn is NH2 [ COO. (CH2)3' N(C4H9)- 2 H2SO4, and is extensively used in dentistry and in ophthalmic surgery. COOH Anthranilic acid, , or o-aminobenzoic acid, is pre- pared either from o-nitrobenzoic acid by reduction, or from phthalic anhydride: O-CO -CO HOH C0 + H2 NH K NH -- -CO -CO Phthalimide -CONH2 -CO -NH2 -COOH (Hofmann K--COOH reaction, p. 133) Plithalamidic acid It is used as a dye intermediate and in the synthesis of indigo. Methyl anthranilate, ,-C CH3, is a constituent of orange blossoms, and is used in perfumery. S03H o-Sulfobenzoic acid , is prepared by the sul- fonation of toluene and the subsequent oxidation of the CH3 group. SACCHARIN Saccharin, CO NH or o-benzoic sulfimide, may be prepared as follows: CH3 CH3 CH3 H2S04 SO3H -s2C NH3 PC15 o-Toluene- o-Toluenesul- sulfonic acid fonyl chloride CH3 COOH -S02NH2 S2NH2 - CO O --H20 NH o-Toluenesulfonamide (When toluene is sulfonated a mixture of o- and p-compounds are, of course, formed. These are separated at the sulfonyl- CH3 chloride stage by filtering them with ice, the p-com- SO2CI pound, being a solid at that temperature, remains on the filter, the o- going through in the form of a thick, oily liquid.) Saccharin was first prepared by Remsen. It is said to be about 550 times as sweet as sugar, and is used as a substitute for sugar in diabetes, and as sweetening agent in mouth-washes, tooth-pastes, etc. The substance has no nutritive value. (Since saccharin itself is not very soluble in water, the sodium salt O >N-Na, which is very soluble, is manufactured.) p-Toluenesulfonylchloride, is employed with p-toluenesul- fonamide as a camphor substitute. p-Toluenesulfonic acid is also used in the manufacture of dyes. p-Toluenesulfonamide is employed in the preparation of chloramine-T. 275 IRA REMSEN (1846- ) FOR MANY YEARS PROFESSOR OF ORGANIC CHEMISTRY AT JOHNS HOPKINS UNIVERSITY (AND LATER ITS PRESIDENT), IS BEST KNOWN FOR HIS WORK ON SACCHARIN (P. 275) AND AS THE AUTHOR OF TEXT-BOOKS ON ORGANIC CHEMISTRY HE HAS DONE MUCH TO FURTHER RESEARCH IN ORGANIC CHEMISTRY IN THIS COUNTRY. 276 READING REFERENCES COOH Gallic acid, 3, 4, 5-trihydroxybenzoic acid, is OH- Q-OH OH found free, or as a glucoside in a number of plants (sumach, gall nuts, etc.), and may also be obtained by hydrolyzing tannins with acid. When heated, CO2 is evolved and pyrogallic acid is formed (p. 242). Gallic acid is used in photography, ink and as an astringent. Tannic acids.-These acids are found in gall nuts and other plants. Their exact constitution is not known, but since, on hydrolysis, they yield hydroxybenzoic acids, particularly gallic OH -OH and protocatechuic, , it is assumed that they are com- COOH plex anhydrides of such acids. The mother substances of these tannic acids are tannins, which are glucosides. (The names "tannic acid " and "tannins" are commonly used interchangeably.) These tannins are found in gall nuts, oak, chestnut, pine, hemlock, etc. They give char- acteristic blue-black or green-black colors with ferric chloride and are valuable astringents. They precipitate proteins and alkaloids. They are largely employed in the making of leather, as mordants in dyeing, and in the manufacture of inks. READING REFERENCES TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), chap. 22 (Drugs). FIscHER-Synthesis of Depsides, Lichin Substances and Tannins. Journal of the American Chemical Society, 36, 1170 (1914). HARRow-Eminent Chemists of Our Time. (1920), pp. 197-216 (Remsen). BRowN-Forest Products. (1919), chap. 3 (Tanning). CLARK-Applied Pharmacology. (1923), pp. 80-84 (The Action of Salicylates). 277 CHAPTER XXVIII NAPTHTHALENE, ANTHRACENE AND THEIR DERIVATIVES So far we have considered aromatic compounds containing the benzene nucleus; but now we begin to discuss compounds containing two or more condensed benzene rings, in which-to take an example-two carbon atoms are common to both rings: H H H-C C C-H I II I H-C C C-H I I H H Naphthalene Naphthalene and anthracene are the most important of such compounds. Naphthalene.-This hydrocarbon is obtained from coal tar in the fraction distilling over between 170-230' (middle or car- bolic oil fraction. See chart facing p. 199); the crude product so obtained is purified by sublimation. Naphthalene crystallizes in lustrous plates, having a m.p. of 800 and a b.p. of 2180. It is very volatile and has a characteristic odor. It is used in the preparation of naphthalene compounds, in moth-balls, as an insecticide and germicide, in the manufacture of phthalic anhy- dride (p. 258), and dye intermediates (p. 316). Naphthalene has the formula C1oHs and on oxidation yields -COOH phthalic acid, , which proves the hydrocarbon to Sc -COOH NAPHTHALENE contain a benzene ring, as well as some side-chains containing two carbon atoms in the o-position with respect to one another. That the actual constitution of naphthalene corresponding to CloHs is or two condensed benzene rings, is suggested by a number of reactions, of which two will be mentioned. Naphthalene, like benzene, can be readily nitrated, yielding nitronaphthalene, and the latter reduced, giving aminonaphtha- lene. When nitronaphthalene is oxidized, we get nitrophthalic acid, but when aminonaphthalene is oxidized, we do not get aminophthalic acid, but just phthalic acid. If we write the structure for nitronaphthalene as 12 NO2 then it is piain that on oxidation, ring (2) must be oxidized to yield nitrophthalic acid -COOH -COOH NO2 whereas if we write aminonaphthalene as NH2 then it is equally evident that ring (1) must here be oxidized to yield phthalic acid HOOC- HOOC- 279 280 NAPHTHALENE, ANTHRACENE AND THEIR DERIVATIVES Obviously, then, there must be two benzene rings in naphthalene- two benzene rings having two carbon atoms in common. Naphthalene has 8 replaceable hydrogen atoms: Since the molecule is symmetrical in structure, positions 1, 4, 5 and 8 are identical, and positions 2, 3, 6 and 7 are identical. We, therefore, have two possible monosubstitution products, a substituent at position 1 (or 4, 5, 8) being known as a- (alpha), and a substituent at position 2 (or 3, 6, 7) being known as P-(beta). For example, Cl , -SO3H a-Chloronaphthalene P-Naphthalenesulfonic acid With disubstitution products, where the substituents are the same, 10 isomers are possible: 1 :2, 1 :3, 1 :4, 1 :5, 1 :6, 1: 7, 1: 8, 2 :. 3, 2 : 6, 2 : 7; but where they are dissimilar, 14 isomers become possible. Many substitution products and derivatives of naphthalene are manufactured, since they are used as dye intermediates, but only a few of these will be discussed here. a-Chloro (or bromo) naphthalene Cl (or Br) is prepared by the direct action of chlorine (or bromine) on boiling naphthalene. (The p-chloro-or bromonaphthalene-is prepared by indirect methods.) On the other hand, when chlorine (from potassium chlorate and HC1) is allowed to act on the hydro- CHC1 CHCI carbon, naphthalene tetrachloride, CCI an addition CHCl product is obtained. NAPHTHALENE Some other reactions are: N02 HN03 a-Nitronaphthalene SI) SO3H a-Naphthalene- sulfonic acid NH2 3H2 a-Aminonaphthalene or a-naphthylamine Heated to 1600 -HSO3H P-Naphthalenesulfonic acid The sulfonic acids are used in the manufacture of naphthols: S03H OH NaOH (fusion) a-Naphthol -SO3H NaOH -OH (fusion) #-Naphthol These reactions, it will be noticed, are entirely analogous to the preparation of phenol from benzenesulfonic acid (see p. 237). The naphthols are very important dye intermediates. a-naph- thol is also used to test for the presence of carbohydrates (p. 164). 0-naphthol is employed internally as an intestinal antiseptic, and externally, in the form of ointment, for the treatment of skin diseases. -O-CH3, 0-naphthyl methyl ether is known as synthetic "yara-yara" and is used in perfumery. The 0-naphthyl ethyl ether is known as synthetic " nerolin" and is also used in perfumery. 281 H2S04 (heated to 80-1000) 282 NAPHTHALENE, ANTHRACENE AND THEIR DERIVATIVES NO OH, -OH, a-nitroso-p-naphthol is used to determine cobalt in quantitative analysis. - C O- , 0-naphthyl benzoate is used inter- nally as an intestinal antiseptic in diarrhea and typhoid fever, -COO- Q-OH -CO 0\ , #-naphthyl salicylate is useful in intestinal fermentations. a-Naphthylamine is prepared from naphthalene: NO2 NH2 O HN03 3H2 and 0-naphthylamine from 0-naphthol: 3- OH + HJNH2 -NH2 (ZnC12) The 0-naphthylamine may also be obtained by heating f-naphthol with ammonium chloride and NaOH in an autoclave at 1600. The naphthylamines are used extensively for the manu- facture of dye intermediates and azo dyes (p. 299). (Just as the NH2 group in aniline, etc., can be diazotized- see p. 229-so can the NH2 group in naphthalene compounds.) Examples of acids derived from naphthalene are: COOH COOH COOH Naptho acid -NaphtCOOH a-Naphthoic acid 0-Naphthoic acid Naphthalic acid NAPHTHALENE and of quinones: 0 =-O 0-b\_ a-Naphthoquinone 6-Naphthoquinone Amphi-Naphthoquinione (The a-variety may be prepared by oxidizing naphthalene with chromic acid in the presence of glacial acetic acid.) CH2 CH2 ("Tetralin," or naphthalene tetrahydride, C CH2 which has been suggested as a motor fuel and solvent, is prepared by reducing naphthalene with hydrogen in the presence of nickel as catalyst. A somewhat similar compound, "decalin," H2 H2 H2s =f -=H2 , has also been suggested as motor fuel and H H2 112 solvent. Many dye intermediates containing different substituents in the naphthalene ring are manufactured. A few of these are: NH2 OH I /I 0 0 SOaH S03H a-Naphthylamine a-Naphtholsul- sulfonic acid or naphthionic acid fonic acid OH OH OH NH2 HO3S- )-S03H HO3S- SO3H 1, 8-Dihydroxy, 3, 6-naphthalene- 1-Amino-8-hydroxy, 3, 6-naphthalene- disulfonic acid or chromiotropic acid disulfonic acid, or H-acid 283 The following chart shows the position of entering substituents in the naphthalene ring. If a hydrogen atom in naphthalene is replaced by C1 Br OH OR NO2 NH2 NHR S03H CN COOH intheposition 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 the new group enters in the position tT 4 4 2? 1 1 5 5or8 5 4 ? 4 8 1 5or8 4 1 5 .5 5 H 50or8 5or8 5 2 1 5 5 5 2 1 4 4 5 5 5 0 6or7 4 8 4 8 2 1 4 8 8 8 8 4 5 5 ? 8 8 8 8 ? 4 6 4 6 2 6 5 4 5 5 5 a 6 5 a 5 8 ? 8 4 8 7 8 6 ? H 6 5 5 6 2 6 5 6 7 6 7 7 2 1 1 2 3 Cl Br NO2 SO3H under 100' SO3H above 1000 NO COOH ANTHRACENE Anthracene, C14Ho1, or 0 00or is separated from coal tar in the fraction which boils over 2700 (see chart facing p. 199). (From this fraction carbazole, and phenanthrene, are also recov- NH ered). The process by which this hydrocarbon is purified is a rather laborious one. The final purification is carried out by sublima- tion with superheated steam (m.p. 2160, b.p., 3600). Anthra- cene comes in the form of colorless, glistening leaflets, having a blue fluorescence. It is used in the manufacture of anthra- quinone and its derivatives. The structure of anthracene has been confirmed by a number of syntheses of the compound, one of which will be given: In the presence of A1C13, two molecules of benzene combine with one molecule of tetrabromoethane to form anthracene (Friedel- Craft's reaction.) H H H Br -C- Br H - (AlCl3) + I + -* H Br -C- Br H- HH H The positions of the replaceable hydrogen atoms are numbered thus: 11 and from its structure it may be seen that positions 1, 4, 5 and 8 bear exactly the same relationship to the molecule. This is also 285 286 NAPHTHALENE, ANTHRACENE AND THEIR DERIVATIVES true of positions 2, 3, 6 and 7, and of 9 and 10. There are pos- sible, therefore, three mono-substitution products; 1, 4, 5 or 8- being known as a-; 2, 3, 6 or 7, as 1; and 9 or 10 as -y (gamma); e.g., a-Chloroanthracene i- The most important none, S03H nthracenesulfonic acid y-Bromoanthracene derivative of anthracene is anthraqui- CO CO which is prepared from anthracene by oxidation with chromic acid (Na2Cr207 and H2S04). (Nitric acid does not give rise to nitro-derivatives with anthra- cene, but converts it to anthraquinone-an indication that the central nucleus in anthracene is somewhat different from the two outer benzene nuclei.) Anthraquinone is manufactured on a large scale, for it is used in the manufacture of dyes (such as alizarin) and dye inter- mediates. It is synthetically produced from phthalic anhydride by condensing the latter with benzene. CO 0+ CO CO CO J o-Benzoylbenzoic a id H2S04 (dehydrat- ing agent) CO CO READING REFERENCE 287 A number of other important anthraquinone derivatives used in the manufacture of dyes are: SO3H CO a-Anthraquinone- sulfonic acid A few other tar are: Phenanthre CIoH14 K9 0 y SO3H C -NH2 #-Anthraquinone- f-Aminoanthraquinone sulfonic acid condensed ring compounds obtained from coal CH2-CH2 ne Acenaphthene C12H10 Chrysene C1sH12 READING REFERENCE BARNETr-T-Anthracene and Anthraquinone. ORGANIC TYPE FORMULAS ALIPHATIC SERIES COLUMN I HYDROCARBONS SATURATED UNSATURATED PARAFFINS= OLEFINES= ACETYLENESO CnHzn+2 CnH2n CnH-rn-2 ALKANES ALKENES ALKI AES H H-C-H METHANE H-C-C-H ETHANE h 1 1 ETHYLENE H H. ACETYLENE C O C. C __OR H A ETHENE C THINE ALKYL HALIDES HR X,HALOGEN H--I R-X R'ALKYL 14-C-Cl CH, ALY HC'H' ~AL-L METHYL CHLORIDE LKYLGROUP MONOCHLOROMETHANIE CnH2n+ 13 ALCOHOLS H H H-c-OH H-C-ONa I! -OH H ALCOHOL GROUP - METHAN_L SODIUM METHOXIDE METHYL ALCOHOL SODIUM METHYLATE H.R R--OH R- C-OH PRIMARYALCOHOL SECONDARY COLUMN If H3C-900 - C=O R-C=O NH2 NjH2 llH2 ACETAMIDE AMIDEGROUP AMIDES H3C-C O R-C=O R-C=O Cl ACYL GROUP x ACETYLCHLORIDE ACYL HALIDES ,SUBSTITUTED ACIDS H3C - COOH H29-COOH H2-COOH H29-COOH Cl OH NH2 *CHLOROACETIC ACID HYDROXYACETIC ACID AMINOACETIC ACID -COOH H2q COOH H2C%COOH CN CYANOACETIC ACID MALONIC ACID CARBOHYDRATE GROUPS H-C-OH H-C-OH OR Cto 'H ALDOSES HWC-OH I C=O H- C-OH H KETOSES AMINES R-C-O- TERTIARY ETHERS H H-CO--H -0- R-O-R l l1 'ETHERGROUP *METHYL ETHER ETHERS ,H " H N-H N-CH3 'CH, 'CH5 , H METHYLAMINE AMMONIA N- P R PRIMARYAMINEE DIMETHYL TRIMETHYLAMINE AMINE) 'H N-' S R T R SECONDARY TERTIARY ,CH3 N-CH., ICH3 ALDEHYDES H-C C~-C:O R-C:O AH A H ETHANAL OR ALDEHYDE GROUP ACETALDEHYDE ALDEHYDES H H H-C-C-C-H PROPAN ONE ACETONE KETONES -C- R-C-R 5 0 KETONE GROUP KETONES 0 ;I a) 0 ACIDS HN-C:O -Q:O R-C:O 0 OH OH OH c: ETHANM1ACID CARBOXYL GROUP ACIDS T OR ACETIC ACID ACID DERIVATIVES H3C-C=O -CzO R-C:O 6N. OM MMETAL 6OM SODIUM ACETATE SALT GROUP SALTS -CO R-C:O H CHoO OR OR METHYLACETATE ESTER GROUP ESTERS H3C-C -C R-CI H3C-C C0 R-C I 1-20 10 a. ACETICANHYDRIDE ANMYORIDE GROUP ANHYDRIDES DERIVATIVES CONTINUED ABOVE -0 R-O-N=O R-N R-O-N 0 -200 NITRITES NITRO COMPOUNDS NITRATES NITRILES6--ALKYL CYANIDES 113C-CmN -C-N ACETON ITRILE OR NITRILE GROUP METHYL CYANIDE R-CSN NITRILES ISONITRILES5---CARBYLAMINES H3C-N=C -NC-N METHYL ISOCYANIDE OR CARBYLAMINEGROUP CARYLAMINES METHYL CARYLAMINE. SULFUR COMPOUNDS HC-SH - SH R-SH METHYL MERCAPTAN MERCAPTAN GROUP MERCAPTANS H,C-S-CH3 -S- R-S-R METHYLSULFIDE THIO-ETHERGROUP THIC-ETHERS R-S-S-R R-S-M R-COSH DISULFIDES MERCAPTIDES THIO-ACIDS R, R, 0 R'. 0 S=O 'S S R' R, '0 HO -0 SULFOXIDES SULFONES SULFONIC ACIDS METALLIC ALKYL COMPOUNDS m Br x N CzH5 MpX MMg.Zn.etc. MAGNESIUM ETHYLBROMIDE R Zn C2H5 RR C2H5MR =METALLIC ALKIDES ZINC ETHYL R COPYRIGHT 1919, BY D. VAN NOSTRAND COMPANY C LUMN I COLUMN If CHAPTER XXIX DYES AND STAINS DYES DYES have a wide application. They are applied to cotton, linen, silk, wool, paper, straw, wood, leather, feathers, hair, fats, waxes, soaps, inks, food, condiments (jams, macaroni, candy), varnishes, paints, etc. In analytical chemistry, dyes are used as indicators (e.g., phenolphthalein, congo red, methyl orange). In histology and bacteriology, they are used for staining micro- scopical preparations (e.g., methylene blue, acid fuchsin, safra- nine, eosin, gentian violet, neutral red, Bismarck brown). Dyes are also used as explosives (picric acid, picrates, trinitro- cresols, etc.); in photography (eosin, erythrosin, etc.); as anti- septics (acriflavine, proflavine, malachite green, etc.). Dyes have been used from the very earliest times. Until the middle of the last century, those used for dyeing and printing were the vegetable dyes, coloring substances from certain insects (as cochineal) and mulloses, and a number of mineral colors. "In 1856, Perkin, in attempts to prepare quinine artificially, found that aniline (a coal tar product) could be oxidized with chromic acid to yield a violet dye, to which was given the name "mauve." This was the first coal tar dye to be prepared, but since then no less than 3000 dyes derived from coal tar products have appeared on the market. The dyes, then, may be either "natural " or "artificial." Among the former are logwood, fustic, Brazil wood, turmeric, natural indigo, etc., and they still find uses. The artificial dyes, however, play a much more important part in the industries. The ones of particular value are "fast " to light, rubbing and washing. Dyes are also classified in accordance with their behavior towards fabrics as "substantive " or "direct " and "adjective " 288 WILLIAM HENRY PERKIN (1838-1907) PREPARED THE FIRST COAL-TAR DYE, "MAUVE" (P. 288), AND IS THEREFORE CALLED THE "FATHER1) OF THE COAL TAR DYE INDUSTRY. 289 DYES AND STAINS or "mordant " dyes. The "direct " dye can be applied directly (without a mordant) to the fabric, usually silk or wool. The "adjective " or "mordant " dye needs a "go-between "-a third substance which attaches itself to the fabric on the one hand, and the dye on the other; this third substance is the "mordant "-"bite into "-(e.g., various aluminium, chromium and iron salts, tannic acid, etc.). The combination of a mordant and a dye is known as a color "lake," the color of the "lake " varying with the type of mordant used. By using different mordants with the same dye, various colored lakes are produced. "Mordant " dyeing is mainly used for cotton goods. (In "direct " dyeing, the fabric is immersed directly in the prepared dye bath, heated to the required temperature, and agitated for a certain length of time.) We cannot in this volume go into the various theories which have been suggested to explain the process of dyeing, beyond merely enumerating them: the chemical theory-a combination of the dye with the components of the fabric or certain constitu- ents of the cell; the mechanical theory, based on adsorption; the solution theory, somewhat like the solution of one metal in another, as in an alloy; and the colloid theory, based on the col- loidal properties of the reacting substances. From the practical standpoint, the classification of dyes depends upon their behavior towards fibers. The dyes are divided into: (1) Acid dyes, which include nitro compounds and the sodium salts of sulfonic and carboxylic acids. These are direct dyes for wool and silk (in an acid bath), but are not adapted for the dyeing of cotton. (These dyes fade rapidly when the fabric is washed with soap or washing powders, but are resistant or "fast " to the effects of sunlight.) (2) Basic dyes, substances which readily combine with acids to form salts. They are "direct " dyes for silk, artificial silk and wool, but not for cotton and linen.. The last two have first to be "mordanted," the mordant used being acid in character (such as tannic acid, for example), since the dye itself is basic. Fabrics dyed with basic dyes fade when exposed to sunlight. (3) Direct cotton dyes, usually sodium salts of sulfonic and carboxylic acids and generally contain the azo (-N=N--) grouping. They are adsorbed by the fiber directly and are used 290 mainly for dyeing cotton material (in the presence of NaCl or Na2SO4). (4) Sulfur dyes-produced from various aromatic organic cmnpounds by the action of sulfur and sodium sulfide. They are used for dyeing cotton and are fairly "fast " to washing. (5) Vat dyes. These dyes are first reduced (generally with sodium hydrosulfite), the fabric being then agitated in the reduced dye bath and exposed to the air (whereby the dye is oxidized). Examples of such dyes are indigo and anthraquinone dyes. They are very stable, being the "fastest " colors known. (6) Mordant dyes, which are generally of a phenolic or acidic character. Here mordants must be used to fix the dye to the fabric. Examples of mordant dyes are the coloring matters of dye woods (such as logwood and fustic) and alizarin. (7) Ingrain dyes. These include substances (such as aniline black and para red) which are really only formed in the dye bath as a result of the chemical combination of two or more compounds. They are mainly cotton dyes. The classification just described is a somewhat empirical one and arose in response to the practical needs of the dyer. There is still another classification, a more scientific one, based on the presence of certain groups in the molecule of the dyestuff. All dyes, in the first place, contain a chromophore, or color-producing group, such as the nitro, -NO2, the azo, -N=N-, the nitroso, -N -NO, the quinoid , CO, CS, CN, I O (azoxy) groups, -N> etc. But before the colored body can become a dye, it must also possess either acidic or basic characteristics, so that it can attach itself to the fiber, or to the tissue (within the cell). These acidic or basic properties are given to the dye when auxochrome groups are present, such as OH, SH, NH2, NHR, NR2, etc. For example, azobenzene, N=N- which is a colored compound, is not a dye, but p-dimethylamino- azobenzene, 291 DYES DYES AND STAINS 0-N=N- O -N=N--N(CH3)2 is a dye. The entire subject of dyes is so extensive, that nothing more than a few members of the class can be mentioned here. How- ever, the latest, and generally accepted classification of dyes will be given, and each type will be illustrated by one or more examples of dyes, stains or indicators in use. (The student should make a point here of noting the presence of chromophore and auxochrome groups in these compounds.) CLASSES OF DYESTUFFS EXAMPLES Nitroso dyes =NOH =0 NOH Resorcin green (Dye) Nitro dyes ONa Na03S-S- -N02 N02 or 0 13 ONa NO2 Naphthol yellow S I (Dye and food color) 292 DYES CLASSES OF DYESTUFFS EXAMPLES OH 02N- -NO2 NO2 Picric acid (Dye and explosive) Stilbene dye SO3H SO3H CH--CH3--NN-C6H3-CH CH-C6H3-N-N-C6 H3-CH SO3H O SO3H Sun yellow 1 . (Dye) Pyrazolone dyes COOH H C=N C6H4-N-N=C SOaNa O=C-N- C6H4 SOs Na Tartrazin 1 (Dye, stain and food color) Azo dyes NH2 N=N- -NH2 HCI Chrysoidine (Dye) 1 Notice the presence of the sulfonic acid grouping, or of its salt, as part of the structure of some of these dyes. The presence of this group increases the solubility of the (lye in water. 293 DYES AND STAINS CLASSES OF DYESTUFFS EXAMPLES 0- N= - N(CH3)2 HCI Butter yellow (Dyc and indicator) NaO3S- -N(CH3)2 Methyl orange (Dye and indicator) NH2 N=N-1 SO3Na NH2 S3Na Congo Red (Dye and indicator) Diphenylmethane dyes C NH-HC1 N(CH3)2 N(CH3)2 Auramine (Dye) 294 CLASSES OF DYESTUFFS EXAMPLES Triphenylmethane dyes C N(CH3)2 N(CH3)2 N(CH3)2 Crystal violet (Dye and stain) N(CH3)2 N(CH3) 2 Malachite green (Dye and stain) Xanthone dyes Cl (C2HI-I)2 O -N(C2H5)2 -COOH Rhodamine B (Dye and stain) DYES 295; DYES AND STAINS CLASSES OF DYESTUFFS Acridine dyes ,-NH2 NH2 Chrysaniline (Dye) Quinoline dyes 0 C S-CH~O-C- N Quinoline yellow (Dye) Indophenol dyes /N (CH)2N- - 0 0 Indophenol blue (Dye) Oxazine dyes (CH3)2NJ C1 Meldola's blue (Dye) EXAMPLES 296 CLASSES OF DYESTUFFS EXAMPLES Thiazine dyes Azine dyes Sulfur dyes N N(CH3)2 S Methylene blue (Dye and stain) H etc. H Sulfur black (Dye) Anthraquinone dyes OH coi -OH Alizarin (Dye and indicator) 297 SDYES ORGANIC TYPE FORMULAS AROMATIC SERIES COLUMN I IBE N ZENE mcCC H (62 H H2 C ~lH >10 12H&< H H H2 HEXAHIYDROBENZENE.TETRAnY)2R8ENZENE DIHYDROBENZENF o 0 CH3 BENZENE METHYL BENZENE-IMIETHYL BENZENE OR TOLUENE OR M.-LENE NAPHTHALENE ANTHRACENE PHENANTHRENE CHALOGEN COMPOUNDS O-CHLO.RaMWUENE O-DIBROMOBENZENE C HC CHCI, Cf-CC3 BENZYL CHLDRIDE BENZAL CHLORIDE BENZO-TRICHLORIDE SULFONIC ACIDS SO3NH 303H SUXFoNII0DkN ONPOEI CNH2 BENZENE SUFNCCD-NNLUFNAIISULFMNIUC ACID NITRO COMPOUNDS NITROBENZENE p-NITROTOLUENE. -NITRONAPHThALENE REDUCTION PRODUCTS OF NITRO CONMPOUNDS 0 0O2 O,N a NITROBENZENE N-*_ I 01CH =AZOXYBENZENE 4ITROSOBENZE E I.I4cH AO$ZN QNHOH C6HgNAh-4CsH5 ~HDAZ)BfNZENE PIIENy'LHYDROXL I~-( NOIAIN j, ANILINE OODAIN ;j N112 HzN-C AMINO COMPOUNDS H N:CN3 NN N~ CH~ 0CNt )-" ANILINE DIMETHYLANIUNE P-TOLUI DIN Efl-NAPHTHYLAM INE DIAZO E:AZO COM POUNDS BENZENEDIAZONQ CHILOR IDE DIAZOEDNE=CHLORIDE Q^-N -N- - N -2 NN"_ DIAZOAMM,EN:ZENE P-AMQlNOA10BENZENE HVDWEAOBENZENE BENZIDIN E HEAVY LINES INDICATE DOUBLE BONDS. COLUMN 11 PHENOLS -ALCOHOLS - ETHERS PHENOL CAEHL RESOYIOL HYDROQUiNONE pQ8Q0L2 PYR7orALLOL 13-NAPHTHOL NHAO QCWZOR(I 00- CBS (Q--C.H, DQ - ( BENZYL ALCOHOL ANISOLE PHENETOLE .PHENYL ETHER ,0ALDE HYDES 12 0IH CO 0-CHCH-CHO BENZALDEHYDE SALICYLIC ALDEHYDE CINNAMIC ALDEHYDE KETONES_, N QtLkNNES e 0 C 06- Q(YQ0~ ACETOPHENONE BENZOPHENONE P-BENZOQUINONE o- EZQINCINE d-NAPHTHOQU INONE /-NAPHTHOQUINONE ANTHRAQUINOINE ACIDS,WND RELATED COMPOUNDS CI 0- COOH -CH=CH-CO01H(N-&WcH BENZOIC ACID PHTHALIC ACID CINNAMICACID PHENYLACETVCACID QCOON& QcoSj,Q- A Q 01 CONKZ2 SODIUM BEN70TE PHENYL BENZOATE BENZOIC ANHYDRIDE BENZAMIDE coo" COO-' COON -~cook QCO NH2 a H Cm714 m-CHLOROSENZOIC ACID AINRAILICACID SALICYLIC ACID O-TOLUJIC ACID Q COO OCN OCOON COH sENzOYL CH LORIDE BENZONITAILE ..-NITIODENZOIC ACID pSULPOSENZOICACID RULES -o-RSUBSTITUTION PRESENT IN POSIT ON ENTERED BY SU BSTITU ENTS POSITION 1, ALKYL Ct 13r I HO2 50~3H ALKY'L 4(Z) 4(Z1 4(2) 4(2) *4.21(3) 412)(3) cl 4 (Z) 442)(3) 412)(3) 4. 4(t1 4 Oir 4 (Z) 412)(3) 4121(3) 4 (Z) 4 14 4 4 412) 4 ONM 4 12) 4121 4(Z) 4121 4121 4(21 NNI2 4(2) 4121 4 4 _4( 2 - .41) NO2 4 (2) 3 3 312.4) 3(2A4 S_- 4 (2) 3 5(2,41 314) LU ri 4(2) 3 3 3 3(2,4) 314) c F, 4 .3 CHARACTERISTIC GROUPS!wNDYESTUFFS CHROMOPHORE GROUPS AUXOICHROME GROUPS -NO = NITROSO) -OH =:HYDROXYL -NO, NHITRO + -NH2 -AMINO -N-N- * Azo + NHR '1SUBSTITUJTED QUIOID-HRz AMINO s03" SULFONIC - * -U4- 4 -e tc . E T O E Cl ~ ()N N' CH A DYE_ HETEROCYCLIC COMPOUNDS FURAN THIOPHIN PYRLE INDOLE o H2 (5NH,Z PYRIDINE PIPERIDINE QUINOLINE LIGHT LINES INDICATE SINGLE BONDS DYES AND STAINS CLASSES OF DYESTUFFS EXAMPLES S N-H HI-N CO CO Indanthrene blue R (Dye) Indigo dyes CO CO X NH/ \NH/\/ Indigo (Dye) While the preparation of all of the above dyes cannot be given here, the principles employed in the synthesis of a few of them will be included. Methyl Orange NH2 N=N-I C1 + H Diazotized coupled with SO3H SO3H N(CH3)2 N=N SOaH N(CH3)2 Methyl orange (sodium salt) 298 DYES Congo Red NH2 NH2 di-diazotized O or tetraazof ized I NH2 Benzidine N=NH C1+Hl- / S03H1 NH2 N=N-C1±Hl- SO3H Naphthionic acid dehydrating agent as ICI or Zn(12 N(C1-T3)2 / \7 N(CH3)2 Color base of Malachite green (colorless) Leueo-base of Malachite green 299 Congo red DYES AND STAINS C1 N(CH 3) N(CH3)2 + H Cl N(( SOH Malachite green Alizarin, K> Oxid. CO Anthraquinone fusion with 3NaOH and oxidizing agent CO P-anthraquinonesulfonic acid ONa CO \-ONa CO/ OH CO O --OH + acid -- CO/' Alizarin (The preparation of phenolphthalein of indigo on p. 316). is given on p. 258 and STAINS Dyes have come into use in bacteriology, because very often various bacteria can be differentiated by "staining " them with dyes. A stain is a dye or any other substance which colors tissues so that they can be submitted to microscopic examination. 300 READING REFERENCES Basic aniline dyes are the type of stains commonly used; these show special affinity for the nuclei of cells. Acid dyes are also sometimes used; these usually have a selective affinity for the protoplasm. Some of the most commonly employed aniline dyes are methylene blue, gentian violet, fuchsin, crystal violet, safranine, etc. The chemistry of the process involved in staining is probably not unlike that which occurs in dyeing; there may be a chemical combination between the dye and the protoplasm of the cell, or a process of adsorption may be involved, or possibly both processes are operative. (Recent research has resulted in the production of a "tripan- red " type of dye, of unpublished composition, known as "Bayer 205," which appears to be the most active trypanocide yet dis- covered. It has been used with success in advanced cases of sleeping sickness.) READING REFERENCES TILDEN-Chemical Discovery and Invention in the Twentieth Century (1916), chap. 21 (Production of Dyes); chap. 30 (Natural Colors). WOOD-Chemistry of Dyeing. RAMSEY AND WESTON-Artificial Dyestuffs. PERKIN AND EVEREST--The Natural Organic Coloring Matters. RoGERs-Manual of Industrial Chemistry. (1921), pp. 1006-1032 (Dyestuffs and Their Applications). WATSoN-Color in Relation to Chemical Constitution. HARROw-Eminent Chemists of Our Times. (1920), pp. 1-19 (Perkin and Coal-tar Dyes). 301 CHAPTER XXX TERPENES AND RELATED SUBSTANCES THE terpenes are complex hydrocarbons, usually with the formula C1oH16, present in, or obtained from, such substances as camphor, oil of turpentine and particularly "essential oils." ("Essential oils " are the products obtained when certain plants- such as the conifer and citrus-barks, leaves or flowers are dis- tilled with steam; or when the oil is pressed or extracted with organic solvents. They are usually sweet-smelling substances containing a number of related organic compounds and are extensively used as flavors, in perfumery and in medicine.) The compounds classified as terpenes fall into several classes: CsHs-hemiterpenes, CloH16-terpenes (true terpenes), C15H24-sesquiterpenes, (CloH16o)-polyterpenes. The terpenes are hydroaromatic hydrocarbons, closely related CH3 CH CH3 CH3 contains a hydrogenated benzene nucleus and either a methyl and isopropyl group, or radicals related to these groups. 302 LIMONENE Some of the more important compounds belonging to the terpene group are as follows: CH3 C HC \\\ CH Pinene, CH3-C , is the chief constituent H2C CH2 / CH of oil of turpentine. Owing to the presence of a double bond, it forms addition products with halogens, halogen acids, nitrosyl chloride, nitrogen peroxide, etc. One such product, pinene hydrochloride (obtained by uniting pinene with hydrochloric acid), is "artificial camphor," which resembles camphor. (When crude turpentine is distilled with steam, pure turpen- tine or "oil of turpentine " collects in the distillate and "rosin," or "colophony," a solid resin, remains in the still. The oil of turpentine is used in paints and varnishes and the rosin is used in soap making, varnishes, sealing wax, etc.) CH3 C Limonene, , is present in oil of lemon, lime, 6tc. CH CH3 CH2 303 TERPENES AND RELATED SUBSTANCES CH3 CH H2C/6\CH2 Menthane, H2CU CH2 CH CH /s\ CH3 CH3 9 10 natural product, but we have related to it. or hexahydrocymene, is not a a number of important substances CH3 CH H12C CH2 Menthol, 2C cH , or menthanol, occurs in oil of \CH "OH CH CH3 CH3 peppermint. It has a peppermint-like odor and finds extensive use as a flavoring agent. CH3 Menthone, , or menthanone, is the ketone cor- C3H7 responding to menthane, and is also found in oil of peppermint. Like other ketones, it may be reduced to a secondary alcohol (in this case to menthol). 304 CAMPHOR CH C H2C CH Terpineol, 2C CH2, is found in essential oils and has an H2C CH2 CH C-OH CH3 CH3 odor resembling that of lilacs. CH3 HC Carvone, , is the principal constituent of oil of H2C CH2 CH C CH3 CH2 caraway and possesses the characteristic odor of this oil. CH3 C H2C C=O Camphor, H3C-C-CH3 is obtained from the HqC CH2 CH camphor tree by steam distillation. It may also be obtained synthetically from pinene hydrochloride (p. 303). It is largely used in the manufacture of celluloid (p. 172) and in pharmaceutical preparations. (The artificial camphors on the market are either pinene hydrochloride or triphenyl phosphate, p. 238. Artificial 305 TERPENES AND RELATED SUBSTANCES camphor does not have the same structure as natural or syn- thetic camphor.) CII3 C /H H2C C Borneol, H3C-C-CH3 iOH is the secondary alco- CH hol obtained from camphor (a ketone) when the latter is reduced. It occurs in nature, being known as "Borneo-camphor," and has a camphor-like odor. The following are the important olefin terpenes: Isoprene, CH2=C--CH=CH2, or 2-methyl-1, 3-butadiene CH3 (see p. 37), is obtained by the distillation of rubber or caoutchouc. Citrene, CH3-C=CH-CH2 CH2-C==CH-CH3, is a ter- CH3 CH3 pene obtained from lemon oil. Geraniol (the alcohol), CH3-C=CH-CH2-CH2-C CH-CH2 OH CH3 CH3 is found in rose and geranium oils; and citral (the aldehyde), CH3-CCH-CH2-CH2-C=CH-CHO, CH3 CH3 in lemon and orange oils. CH3 Citronellal, CH\CCH 2CH2 CH2 CH CH2 - CHO occurs CH2/ CH3 in oils of citrus fruits. 306 TABLE OF ESSENTIAL OILS Oil Allspice Angelica Root Angelica Seed Anise Birch Bitter Almond Camphor Caraway Cedar Wood Celery Seed Cinnamon Bark Citronella Clove Cognac Eucalyptus Fennel Garlic Geranium Ginger Guaiac Wood Hops Jasmine Juniper Berries Lavender Lemon Lime Mustard Neroli Nutmeg Onion Orange Pepper Peppermint Rose Sassafras Spearmint Thyme Tolu Turpentine TABLE OF ESSENTIAL OILS Chief Known Constituents Eugenol; sesquiterpene Phellandrene; valeric acid Phellandrene; valeric acid Anethole; anisaldehyde Methyl salicylate Benzaldehyde; hydrocyanic acid; phenyloxyaceto- nitrile Camphor; borneol; pinene Carvone; d-limonene Cedrene; cedar camphor Limonene; phenols Cinnamaldehyde; eugenol Geraniol; citronellal Eugenol Esters of caprylic acid Phellandrene; cineol Anethole; fenchone Allyl propyl disulfide; diallyl disulfide Geraniol; citronellol Phellandrene Guaiacol Humulene; geraniol; terpenes Benzyl acetate; linalol Pinene; cadinene; juniper camphor Linalyl acetate; linalol IAmonene; phellandrene; citral; citronellol; geranyl acetate; linalol d-Limonene; citral; methyl anthranilate Allyl isothiocyanate Linalyl acetate; linalol; geraniol; limonene Myristicin; pinene Allyl propyl disulfide Limonene Phellandrene; dipentene Menthol; menthyl esters; menthone Geraniol; citronellol; geranyl acetate Safrol; eugenol; camphor; pinene; phellandrene Carvone; limonene; pinene Thymol; carvacrol; cymene; linalol; borneol Esters of benzoic and cinnamic acids Pinene 307 TERPENES AND RELATED SUBSTANCES Valerian Borneol; bornyl formate, acetate and isovalerianate; piriene; camphene Wintergreen Methyl salicylate Ylang-ylang Linalol; geraniol; benzoic esters; methyl ester of p-cresol. (Oil of Chenopodium, an old household remedy for worms, is a mixture of various terpenes.) READING REFERENCES TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), chap. 23 (Perfumes and Essential Oils). DUNCAN-Some Chemical Problems of Today. (1911), chap. 7 (Camphor). DUNCAN-The Chemistry of Commerce. (1907), chap. 8 (Floral Perfumes). SLossoN-Creative Chemistry. (1920), chap. 5 (Synthetic Perfumes and Flavors). GILDEMEISTER AND HOFFMANN-The Volatile Oils. ROGERS-Manual of Industrial Chemistry. (1921), pp. 766-802 (Essential Oils, Synthetic Perfumes and Flavoring Materials); pp. 803-814 (Turpentine and Rosin). BOGERT-The Flower of the Organic Chemist: Perfumes Natural and Synthetic. Journal of Industrial and Engineering Chemistry, 14, 359 (1922). POWER-The Distribution and Characters of Some of the Odorous Principles of Plants. Journal of Industrial and Engineering Chemistry, 11, 344 (1919). HEPBURN-Recent Progress in the Chemistry of the Terpenes and Camphors. Journal of the Franklin Institute, Feb., 1911. ANoN.-Turpentine. (Agricultural Bulletin 898.) Government Printing Office, Washington. CLARK-Applied Pharmacology. (1923), chap. 7 (Anthelminthics- Oil of Chenopodium, etc.) 308 CHAPTER XXXI HETEROCYCLIC COMPOUNDS THE "cyclic " or "ring " compounds so far considered, with a few exceptions, such as succinic anhydride, lactones, etc., have contained the same elements within the ring (in this particular case, carbon atoms; hence carbocyclic). There are, however, very many compounds containing "cycles" in which elements other than carbon are also present; these are known as hetero- cyclic, for example, CH2-CH2 CH-CH CH-CH CH-CH I I II I II I I II CO CO CH CH CH CH CH CH \o / \S/ o/ \N/ Succinic anhydride Thiophene Furan H Pyrrole CH2 H2C , CH2 N N N Pyridine Quinoline H Piperidine or Hexahydropyridine H-N-C=O H O= C C-N/ | 1 1 >C=0, etc. H-N-C-.N' Jric acid or 2, 6, 8-triketopurine (trioxypurine) CH-CH Furan, I I , or furfuran, occurs in pinewood tar. Its CH CH \o0/ HETEROCYCLIC COMPOUNDS CH-CH most important derivative is furfural, 11 1I or furfur- CH C-CHO, \o/ aldehyde, which may be obtained from a pentose sugar, or pen- tosans, when boiled with hydrochloric or sulfuric acid (see p. 161). (This serves as the basis for the detection and estimation of pentoses and pentosans.) Commercially, furfural is prepared from corn and maize cobs and other waste cereal products rich in pentoses or pentosans. It is used in the manufacture of synthetic resins, disinfectants, deoaorizers, solvents, etc. The general properties of furfural are similar to those of benzaldehyde. On CH-CH oxidation, we get pyromucic acid, I1 1| , which, as its CH C-COOH \o/ name implies, may also be prepared by heating mucic acid, COOH-. (CHOH)4COOH, an oxidation product of galactose or lactose (p. 168). (The Molisch test for carbohydrates-p. 164, is said to be dependent upon the production of furfural.) CH-CH Pyrrole, 1I 11 , is present in coal tar and in bone oil CH CH \N/ H (Dippel's oil), which is a product of the destructive distillation of bones. (The pyrrole ring is present in a number of alkaloids.) CH2-CH2 It may be reduced to pyrrolidine, I , a carboxylic acid CH2 CH2 H CH2-CH2 derivative of which is proline, I I , one of the CH2 CH. COOH H decomposition products of .proteins (p. 146). 310 I-C----C--I Iodol, II I , or tetraiodopyrrole, is an antiseptic, and I-C C---I \N/ H is sometimes used in place of iodoform. Other nitrogen-containing compounds are: HC-CH H2C--CII 112C--CH 1I 11 I I1 HC N H2C N OC N \N1 \N/ \N/ I I I H H H Pyrazole Pyrazoline (dihydropyrazole) Pyrazolone A derivative of the last compound is antipyrine: HC4==3C-CH3 OC5 2N-CH3 C6H5 or 2, 3-dimethyl-l-phenyl-5-pyrazolone, which is made by con- densing acetoacetic ester with methylphenylhydrazine: CH3-C 0 H IN-CH3 CH.IHCO OC2H5 H N--CGH5 Antipyrine is used as an antipyretic and analgesic. (The 4-dimethylamino derivative of antipyrine is known as "pyrami- don " and is used for similar purposes.) Phenyl methyl pyrazolone is used in photography and is known as "developer Z." CH-CH Thiophene, I II , occurs in crude benzene and is the CH CH S mother-substance of many sulfur-containing compounds, b.p. 840. It is separated from benzene by repeated extraction with H2S04 (thiophene is readily sulfonated, while benzene is not), and may IODOL 311 HETEROCYCLIC COMPOUNDS be identified by the "indophenin " reaction (a mixture of isatin, thiophene and H2S04 gives a blue color). Pyridine, (which may be looked upon as benzene in N which one CH is replaced by N), is found in coal tar in the "light oil " fraction, in tobacco smoke, in Dippel's oil, and in crude ammonia. Pyridine is soluble in water, the solution being slightly alkaline in reaction. It has a characteristic, putrid odor and is an extremely stable substance, not being attacked by chromic acid (Cr03) or nitric acid. It is used to denature alcohol. (The pyridine ring is present in a number of alkaloids.) The positions in pyridine are numbered Iy a 6 21 N The compound has three mono-substitution products of the type X N N N When reduced, pyridine yields piperidine, a substance which occurs in pepper and has a pepper-like odor. CH2 CH2 CH2 I I CH2 CH2 NH/ Quinoline, 0 , a condensation of one benzene and one N 312 pyridine ring, is present in coal tar and bone oil, and may be prepared by the Skraup's reaction, in which a mixture of aniline, glycerol, H2SO4 (dehydrating agent) and nitrobenzene (oxidizing agent) are heated: N =C-Ci=CH2 N'CH CH H nitrobenzene Acrolein C (from glycerol and H2SO4) H Acrylaniline N 702 On oxidation, quinoline yields quinolinic acid, -COOH O -COOH N (What does naphthalene yield on oxidation?) (The quinoline ring is present in certain alkaloids.) Isoquinoline, , is found in coal tar. (The iso- quinoline grouping is present in a number of alkaloids.) Coumarin, CO , is the sweet-smelling constituent of 0 tonka bean, and freshly-mown hay. It is used extensively in flavoring extracts, flavoring tobacco, perfumery and as an adulter- ant for vanillin. It is made by the following series of reactions: 0-OH + CHC13 + 3NaOH --OH )II Reimer-Tiemann -CHO Reaction (p. 270) Salicylaldehyde COUMARIN 313 HETEROCYCLIC COMPOUNDS + CH3COONa and Acetic anhydride - (Perkin reaction p. 257) I0 0 -CH=CH-CO OH0 o-Hydroxycinnamic acid Coumarin Indole, , represents a condensation of the benzene N H and pyrrole rings, and is an intestinal product formed when proteins putrify. Indole is a highly toxic substance and is de-toxified by being converted into indican, in which form it is eliminated in the urine: CH 0O C(OH) + H2S04 CHo N N H H Indoxyl C(OSOH) + Ksalts C(O SO3K) N N H H Indoxyl sulfuric acid Indoxyl potassium sulfate or indican (The amount of indican in the urine is a rough indication of the extent of putrefaction within the intestine.) Indigo is a natural product obtained from the indigo plant (in which it occurs as the glucoside "indican ")-which grows in tropical countries-and is one of the oldest and best known vat dyes. Its synthesis in the chemist's laboratory (by Baeyer) 314 JOHANN FRIEDRICH WILHELM ADOLF BAEYER (1835-1917) RESPONSIBLE FOR THE SYNTHESIS OF INDIGO (P. 314), WAS ONE OF THE MOST FRUITFUL WORKERS IN ORGANIC CHEMISTRY DURING THE NINETEENTH CENTURY. 315 HETEROCYCLIC COMPOUNDS ranks as one of the great achievements in the history of organic chemistry. It may be produced artificially by the following series of reactions: S CO N -NH -CO 00 O-CO -CO>NH Naphthalene Phthalic anhydride Phthalimide H20 COOH jj-CONH2 Phthalamidic acid reac NaOCI (--COOH Hofmann --NH H + C11 CH2.COOH i, 133 ) Anthranilic acid or o-aminobenzoic acid Chloroacetic acid COOH -NH-CH2-COOH Phenylglycine-o-carboxylic acid NaOH(fusion) (-H20) Oxid. (air) (air) C(OH) -C0a /C. COOH K N H Indoxylic acid Indox! CO CO NH NH Indigo (OH) yl (enol form) 316 L, p. -V. On a commercial scale at the present time, indigo is prepared as follows: NH[ CH2COOH NH*CH2,C OH Heated -t with H NaNH2 (Sodamide) Phenylglycine NH aNH co / Indoxyl (keto form) NH air oxidation (2 mols.) Indigo (The disodium salt of indigodisulfonic acid, known also as "indigo carmine," is used as a food color.) , or 0-methylindole, is also a putre- factive product formed in the intestine and its fate in the body is similar to that of indole. It is present in feces and has an extremely disagreeable odor. Tryptophan, -CH- COOH I , or a-amino-o-in- NH2 dolepropionic acid, has already been referred to under amino acids (p. 142). Skatole, TRYPTOPHAN 317 READING REFERENCES READING REFERENCES LowRY--Historical Introduction to Chemistry. (1915), chap. 17 (The Rise of Organic Chemistry). TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), Chap. 32 (Organic Chemistry). HENDRICK-Everyman's Chemistry. (1917), part 3 (Organic Chemistry). SLossoN-Creative Chemistry. FINDLAY-Treasures of Coal Tar. STEwART-Chemistry and its Borderland. (1914), chap. 2 (The Allies of Chemistry among the Sciences); chap. 3 (The Relation between Chemistry and Industry); chap. 13 (Chemical Problems of the Present and Future). DUNCAN-The Chemistry of Commerce. (1907), chap. 9 (The Making of Medicines). KENDALL-Chemistry of the Thyroid Secretion. Harvey Society Lectures, 1920-21 (Lippincott), pp. 41-58. SLossoN-The Story of Insulin. World's Work, Nov., 1923, pp. 87-95. RUSSELL-The A. B. C. of Atoms. MILLS-Within the Atom. FALK and NELSON-The Electron Conception of Valence. Journal of the American Chemical Society, 32, 1637 (1910). LANGMUIR-Types of Valence. Science, 54, 59 (1921). HARRow--Contemporary Science. (1921), pp. 23-33 (The Structure of Atoms and its Bearings on Chemical Valence-by Langmuir). NoYEs-Valence. Science, 49, 175 (1919). HETEROCYCLIC COMPOUNDS CH Two other heterocyclic compounds are acridine, present in coal tar, and carbazole, or dibenzopyr- role, present in anthracene oil. Carbazole is used in the manu- facture of dyes. Two important derivatives introduced in medicine: 7 2 H2N ,5 3 NH2.HCl N CH3 C1 Acriflavine or 3, 6-diamino-10-mthyl- acridiniumn chloride hydrochloride of acridine have recently been H2N NH2 H S04H Proflavine or 3, 6-diaminoaridinium hydrogen sulfate They are strongly antiseptic and non-toxic. 318 CHAPTER XXXII VEGETABLE ALKALOIDS VEGETABLE alkaloids are basic nitrogenous substances which occur in plants usually in combination with organic acids (citric, tartaric, oxalic, malic, etc.) and which are characterized by power- ful physiological activity. They contain the elements C, H, N or C, H, 0 and N and are complex in constitution, generally con- taining pyrrole, pyrrolidine, pyridine, quinoline or isoquinoline groups in their structure. Only a very brief presentation of the subject can be given here. Alkaloids occur in dicotyledonous plants. Most of them are crystalline (coniine and nicotine are liquids) and most of them are levorotatory. They are insoluble in water, soluble in alcohol, ether, chloroform, etc., to a greater or less extent, form water- soluble salts with acids, have a bitter taste and some are exces- sively poisonous. Most of the alkaloids are used in the form of salts, such as hydrochloride, nitrate, bisulfate, sulfate, phos- phate, etc. The following substances, known as "alkaloidal reagents," precipitate alkaloids from their aqueous or acid solutions; tannic acid, potassium-mercuric iodide (KI+HgI2), phosphomolybdic acid, picric acid and phosphotungstic acid. (The "alkaloidal reagents " are quite often used to precipitate proteins.) Color reactions are frequently used to identify certain alka- loids. The method of extraction from plants often consists in extract- ing with acidified (HC1 or H2S04) water and reprecipitating with bases. The number of alkaloids known is very large; only a few of the more important ones can be mentioned here. VEGETABLE ALKALOIDS CH2 H2C CH2 Conine, H2C CH CH2CH CH3, or a-propylpiperidine, N H is obtained from the seeds of spotted hemlock and has been produced synthetically. It is very poisonous, has a disagreeable odor and an acrid taste. (Chemically, it is the simplest alkaloid.) CH2- CH2 Nicotine, I I , or a-pyridyl-N-methyltetrahy- CH CH2 N CH3 dropyrrole, is present in tobacco leaves and is used as an insecti- cide. Piperine, C171119N03, occurs in pepper, from which it is extracted. Atropine, C17H23N0O3, obtained from the Deadly Nightshade (belladonna), is used as a mydriatic (dilating the pupil) in oph- thalmic surgery. Homatropine, an artificial alkaloid derived from atropine, dilates the pupil more rapidly than atropine and the effect is not as lasting. Cocaine, C17H21N04, is contained in coca-leaves. It is used as a local anesthetic in minor operations, though, owing to its extreme toxic properties, it has been largely replaced by novocaine, butyn, etc. (p. 274). Quinine, C20H24N202, is obtained from cinchona bark, etc. It is used in the treatment of malaria, as a "bitter " (to increase appetite), to reduce fever, etc. Cinchonine, C19H22N20, from cinchona bark, resembles quinine in its physiological properties, though its effects are not so pronounced. Strychnine, C21H22N202, and brucine, C23H26N204, occur together in the seeds of nux vomica and in St. Ignatius' beans. Strychnine is an extremely poisonous substance, acting on the spinal cord and producing characteristic convulsions. In very 320 READING REFERENCES small doses, it is used as a tonic, to increase the appetite, as a heart stimulant and in various forms of paralysis. Brucine acts similarly. Morphine, C17H1iN03, is the chief alkaloid of opium (which is the dried juice of the seed capsules of a variety of poppy). It is used as an analgesic and as a soporific. Heroine is a diacetyl derivative of morphine. Its effects are, in general, similar to those of morphine. It is used as a sedative and to lessen coughing. Narcotine, C22H23N07, and codeine, C18sH21N03, are also present in opium and are closely related to morphine. Dionine is an artificial alkaloid made from morphine (ethyl morphine) and is used to produce sleep and relieve pain. Pilocarpine is the active principle obtained from the leaves of Pilocarpus jaborandi, a Brazilian shrub. It is used principally to increase perspiration. Emetine, the active alkaloid of ipecac, is used in the treatment of amoebic dysentery (because of its destructive action on amoebae) and also in the treatment of pyorrhoea alveolaris, an infected condition of the teeth sockets. READING REFERENCES PICTET AND BIDDLE-The Vegetable Alkaloids. BARBOUR-Local Anesthetics. Science, 51, 497 (1920). CLARK-Applied Pharmacology. (1923), chap. 5 (The Action of Quinine in Malaria). 321 CHAPTER XXXIII ARSENIC AND MERCURY COMPOUNDS OF THE AROMATIC SERIES ARSENIC and mercury compounds, particularly the former, have found wide application in the treatment of diseases caused by protozoa (such as in syphilis). The organic combinations of these metals have an advantage over the inorganic compounds in that they are less toxic to mammals and more toxic to pro- tozoan parasites. ARSENIC COMPOUNDS NH2 Arsanilic acid, , or p-aminophenylarsinic acid, may As OH OH be regarded as being derived from arsenic acid, AsO(OH)3, in which one OH group is replaced by aniline, and is prepared by combining aniline with arsenic acid. The monosodium salt is known as "atoxyl " and "soamin " and, though used at one time in the treatment of syphilis, relapsing fever, etc., it is now chiefly of interest as an intermediate in the preparation of salvarsan. As=As Arsenophenylglycine, HOOC . H2C . NH NH. CH2. COOH ARSENIC COMPOUNDS was introduced by Ehrlich as a substance even less toxic than atoxyl and of a higher trypanocidal power. OH OH Salvarsan, HCI -NH2 HC1-2H20 or 3,3'-diamino-4,4'-dihydroxyarsenobenzene dihydrochloride, known also as arsphenamine and "606," was first synthesized by Ehrlich and introduced by him for the treatment of syphilis. One method of preparing it is as follows: NH2 + H3AsO4 NH2 I OH OH OH diazotization C1 N N HOH AsO(OH)2 OH + HNO3 AsO(OH)2 p-Hydroxy- phenylarsinic acid OH Reduction (Sodium hydrosulfite) 1(OH)2 OH OH H2N- -NH2 As===As + 2HC1 323 ARSENIC AND MERCURY COMPOUNDS OH OII HC1.H2N- -NH2 - HC1 As=As Salvarsan While we cannot, in this book, enter into a prolonged discus- sion regarding the interesting question of the effect of chemical structure upon physiological action, Ehrlich's discovery of sal- varsan deserves a few words of comment. When Ehrlich first began his celebrated research, he was aware of the fact that trypanosomes-a group of parasites-are killed by a number of dyes and a number of organic arsenic compounds, of which "atoxyl " was the most important. This compound contains pentavalent arsenic. The important discovery was made that although it would cure animals of trypanosomiasis, it had no toxic action upon trypanosomes in vitro. After many trials with many arsenical compounds, Ehrlich was in a position to formulate this general rule: that only compounds containing trivalent arsenic were effective in killing trypanosomes, and that the effectiveness of compounds containing pentavalent arsenic depended upon their reduction in the body to the trivalent form. The most efficient substances were found to be compounds con- taining trivalent arsenic joined to a benzene ring and containing also an amino group. This was later still further improved upon by the discovery that the most effective compounds were those containing an OH group in the p-position, an amino group, and arsenic-as in salvarsan itself. Salvarsan, that is the dihydrochloride salt, is soluble, but it forms an acid solution, and is irritant and toxic. By the addition of two gram molecules of NaOH to one of salvarsan, the neutral base is obtained: OH OH H2N-0 0-NH2 As --As 324 ARSENIC COMPOUNDS This is insoluble. Upon the further addition of two gram molecules of NaOH, the sodium salt is produced: ONa ONa H2N0 O0-NH2 As=As and this is soluble in water. It is the form of salvarsan generally used. OH OH H2N- -NH CH2 .0. SONa Neosalvarsan, or sodium As=As 3,3'-diamino-4,4'-dihydroxyarsenobenzene -N-methylenesulfinate, is also known as neoarsphenamine or " 914 " and was intro- duced by Ehrlich because of its greater solubility than salva- rsan. It is prepared by combining salvarsan with sodium formal- dehyde sulfoxylate. (HOCH2 - OSONa) Silver salvarsan and silver neosalvarsan have the same uses as salvarsan, but it is claimed that the presence of silver in the molecule raises the toxicity to parasites without increasing the toxicity to mammals. "Luargol," which contains antimony in addition to silver and arsenic, is another salvarsan derivative for which therapeutic claims have been made. "Galyl " is a salvarsan derivative containing phosphorus in addition to arsenic. Sulfarsenol (Sulfarsphenamine), OH OH NaO. SO2. CH2. HN-NH CH2 . SO2-ONa, As= As 325 ARSENIC AND MERCURY COMPOUNDS or disodium 3,3' - diamino - 4,4' - dihydroxyarsenobenzene - N - di- methylenesulfonate, is similar in its uses to neosalvarsan, but it is claimed that its solutions are more stable in the presence of air. OH As-O-ONa ("Tryparsamide," I , recently synthesized by Jacobs and NH CH2CONH2 Heidelberger, has been successfully applied in the treatment of human sleeping sickness.) (CGH5)2As-C1, diphenylchloroarsine, was used as a "sneeze " gas in the war. MERCURY COMPOUNDS /oHg -COO Mercuric salicylate, is used as an antiseptic and antisyphilitic. Mercuric benzoate (C6H5-COO)2Hg, is also used in treating syphilis and gonorrhea. "Mercurochrome-220," a complex mercurial derivative of fluorescein, has recently been introduced as a very active germi- cide. READING REFERENCES STEWART-Chemistry and Its Borderland. (1914), chap. 4 (Immuno- Chemistry and Some Kindred Problems). RAIZISS AND GAVRON-Organic Arsenical Compounds. WHITMORE-Organic Compounds of Mercury. HIRSCHFELDER-The Influence of Modern Chemistry on Pharmacology. Journal of Industrial and Engineering Chemistry, 15, 455 (1923). DALE-Chemotherapy-Physiological Review, 3, 359 (1923). MORGAN-Organic Compounds of Arsenic and Mercury. 326 CHAPTER XXXIV A BRIEF OUTLINE FOR THE IDENTIFICATION OF ORGANIC COMPOUNDS THE identification of an organic compound is not a simple matter. We have no methods quite as clearly defined as those of inorganic chemistry. In the identification of an organic compound, the first step is to make certain that the compound is in a pure state-a fact which may very often be determined by ascertaining the boiling point or melting point, or by associating the compound with some other physical constant, such as specific gravity, etc. In the next place, an elementary analysis should clearly indi- cate the elements present in that compound. Once this is determined, certain limits are immediately set as to the kind of compound it can be. For example, a compound which upon analysis shows the elements C, H and 0 only, cannot be an amine. The classification of organic compounds and many of their most characteristic reactions are intimately bound up with the presence, within the molecules of these compounds, of various "groups," such as OH, NH2, COOH, etc. In this chapter the attempt will be made to give a brief r6sume of some of the reac- tions used for identifying such groups. Incidentally, this chapter ought to serve, to some extent, as a review. Hydrocarbons.-Usually, these are colorless gases, liquids or solids, insoluble in water and soluble in alcohol and ether. (Where tests reveal that no elements other than carbon and hydrogen are present, the indications would immediately point to the presence of a hydrocarbon.) The paraffin hydrocarbons are very inert substances. The olefins add two bromine atoms to form saturated compounds, and the acetylenes generally respond to the 327 CHAPTER II SATURATED HYDROCARBONS OR PARAFFINS AND PETROLEUM As its name implies, a hydrocarbon is a compound containing hydrogen and carbon. Methane, CH14, is the simplest compound of the hydrocarbon group. Occurrence.-The decomposition of vegetable and animal matter gives rise to this gas. One of the gases arising from marshes is methane, hence its name "marsh gas." It is also one of the gases produced in intestinal putrefaction. It forms a large percentage of the constituents found in natural gas (80 per cent and above) and coal gas (30-40 per cent). Fires and explosions in coal mines are mainly due to mixtures of methane and air. Preparation.-Methane may be synthesized from its elements by passing hydrogen over carbon in presence of nickel (catalyst) at 475'. C+2H2 -- CH4 It may also be obtained by the action of water on certain carbides, such as aluminium carbide: A14C3+12H20 --> 3CH4+4AI(OH)3 This reaction is of interest since it led Moissan, the French chem- ist, to speculate on the origin of natural gas. He held this to be due to the action of water on various metallic carbides. (It must be remembered that methane is not always the product formed when water acts on a carbide. The student will recall that water acts on calcium carbide, for example, to give acetylene.) The laboratory method depends upon heating a mixture of fused sodium acetate and soda lime (NaOH+CaO): CH3 I COONaNaaO H - - CH4+Na2C03 18 328 THE IDENTIFICATION OF ORGANIC COMPOUNDS formation of metallic acetylides. The aromatic hydrocarbons may, as a rule, be nitrated, to form nitro derivatives: CGH + HONO2 -> C6Hs.NO2 + H20 Benzene Nitrobenzene Where the aromatic compounds contain a side-chain (as a'CH3 group, for example), this can be oxidized (by chromic acid or potassium permanganate or dilute nitric acid) to the carboxyl group. The hydrocarbons with condensed benzene nuclei (such as naphthalene, anthracene, etc.) are solids and may be identified by their oxidation products and, very often, by the fact that they form well-defined picrates (with picric acid) with definite melting points. The terpene hydrocarbons (such as pinene) present many difficulties when attempts are made to isolate them. Sometimes a number of physical properties (boiling point, density, specific rotation, etc.) prove helpful. Halogen compounds.-The aliphatic compounds are almost non-ionizable and practically insoluble in water. The alkyl chlorides are lighter than water while the bromides and iodides are heavier. They are hydrolyzed to the corresponding alcohols; e.g., alkali C2H5 Br + H OH - C2H5OH + HBr With the aromatic halides, where the halogen is attached to the benzene nucleus, we get substances which are either liquids or solids, with a faint, agreeable odor, and insoluble in water. They are stable compounds and do not, for example, react with potas- sium hydroxide. They are utilized in the Fittig synthesis. The aromatic halogen compounds, with the halogen in the side-chain, behave similarly to the aliphatic halogen compounds and possess lachrymatory properties. Alcohols.-As a rule, the monohydroxy alcohols are colorless liquids, neutral in reaction and some of them have a characteristic odor and taste. The solubility in water decreases with increas- ing molecular weight. The polyatomic alcohols are oily liquids or crystalline solids, .soluble in water, and less soluble, or alto- gether insoluble in ether. Primary alcohols when oxidized (with chromic acid, for example), give first an aldehyde and then an acid; secondary alcohols yield ketones; and tertiary alcohols break down into ALDEHYDES AND KETONES carboxylic acids containing fewer carbon atoms than the original compound. The OH group is very often identified by forming esters, either with acetyl chloride or acetic anhydride; e.g., R-OH + (CH3CO)20 -- CH3.COOR + CH3COOH Many of these esters have characteristic odors and by sub- mitting them to a quantitative hydrolysis, it becomes possible to determine whether the original compound contains one or more OH groups. (For every OH group, one acetyl group is used.) Phenols.-These are usually crystalline solids. (The solubility in water increasing with the number of OH groups present in the ring.) They are weak acids, being dissolved in alkalies forming salts. Nearly all phenols give a precipitate of a polybromophenol when treated with bromine water; e.g., C6H5OH + 3Br2 -- C6H2(OH)Br3 + 3HBr and yield deeply colored solutions with ferric chloride. Many give the Liebermann test (a deep blue or green color, when the phenol is dissolved in cold cone. H2S04, and a little NaN02 added). (This test is also used for identifying the nitroso group.) Phenols, like alcohols, combine with acetic anhydride to form esters; they also form esters with acyl chlorides and these can be identified by their melting or boiling points; e.g., -CO ICl + H O- 3-COOC6H5 + HC Ethers.-These are neutral, chemically inactive liquids. They are often identified by their boiling points, or by the follow- ing reaction: R--O-R + 2HI heated -- 2RI + H20 Aldehydes and Ketones.-The lower aldehydes are liquids pos- sessing a characteristic odor, and, unlike ketones, reduce Fehling's or ammoniacal silver nitrate solution. For purposes of identifi- cation, aldehydes and ketones may be combined with hydroxyl- amine to form oximes, with phenylhydrazine to form phenyl- 329 330 THE IDENTIFICATION OF ORGANIC COMPOUNDS hydrazones, and with semicarbazide (aminourea) to form semi- carbazone; e.g., CH3 -CH 0 + H2 INOH -- CH -CHI: NOH + H20 C= 0±1c NNHC6H5 -i C : N-NHC6eH + H20 CHa3 CH3 -CH 0 + H2 N-NHCO-NH2 - -CH NNI-NH CO - NH2 1+ H20 Benzaldehyde scminicarbazone Most aldehydes give the Schiff test (restoring the pink color to a solution of magenta which has been decolorized with S02). Carboxylic acids.-The lower aliphatic monobasic acids (as formic and acetic) are liquids, soluble in water, but the solubility decreases with increasing molecular weight. The higher members (like palmitic and stearic) are solids, insoluble in water. The aliphatic polybasic acids (like oxalic and succinic) are solids, soluble in water. Many of the aromatic acids (like benzoic and o-toluic) are not very soluble in cold, but more so in hot water. The acidity of the substance may be determined by titrating with standard alkali. The conversion of the acid to the cor- responding ester (with alcohol and a dehydrating agent) and the elimination of the carboxyl group (in the form of C02) by heating with soda lime, are often of help in identifying the acid. Often the acid is converted to its acyl halide; e.g., C2H5.COOH + PCI5 -- C2H5-COCl + POC13 + HCI Aromatic sulfonic acids.-As a rule, these are soluble sub- stances, difficult to crystallize. For purposes of identification, the corresponding amide is prepared by first forming the sul- fonchloride with PC15 and then converting the latter to the amide- with definite m.p.-: SO3H PC15 -SO2 - Cl HNIH2 -SO2 - NH2 00>I ACID ANHYDRIDES Fusion with alkali to form the corresponding phenol is also sometimes employed: (>-S03Na K -ONa 3N + 2NaOH -- K + Na2SO3 + H20 Acid anhydrides.-As a rule, the aliphatic compounds are colorless liquids, insoluble in water and soluble in alcohol and ether. The aromatic compounds are solid. They are usually identified by hydrolyzing them to the corresponding acids or salts; e.g., C.f; 3- CO o + H 2C,COOH CH, -C HO CH3-CO HO - 2CI3COOH Acyl halides.-These are pungent-smelling liquids, easily convertible (hydrolysis) into the corresponding acids; e.g., CH3COICl + HJOH -- CH3COOH + HCl Acid amides.-These are, as a rule, well defined, crystalline substances. They can be hydrolyzed with boiling alkali to the corresponding acids (salts); e.g., alkali CH3 COI NH2 + H OH -- CH3COOH + NH or Co,5 - CONH2 + HONO --- CH - COOH + N2 + H20 Acid imides, like the amides, are hydrolyzed by boiling with alkalies: CH2-CO HOH CH2 CONH2 HOH CH2-COOH I NHI CH2-CO CH2- COOH CH2-COOH Esters.-These are volatile compounds, insoluble in water, with agreeable odors. The esters may be hydrolyzed with alkali; e.g., CHaCOOI C2H5 + HO H --> CH3COOH + C2HsOH 331 332 THE IDENTIFICATION OF ORGANIC COMPOUNDS Quinones.-These are colored compounds (yellow or red). The p-benzoquinone is volatile with steam. As a rule, they can be reduced; O OH red. 0 Carbohydrates. These are solids soluble in water (except the polysaccharides,- such as starch, etc.). Among the poly- saccharides, starch gives a blue color with iodine, and glycogen and the dextrins, a violet to a violet-red. The sugars (lactose, maltose, galactose, levulose, glucose) reduce Fehling's solution and form osazones with phenylhydrazine. Sucrose or cane sugar is a notable exception. They are optically active. Glucosides.-On hydrolysis, these yield glucose, in addition to one or more substances; e.g., - IOC6H10n + HOH 1 glucose + -OH J-CH20H -CH20II Salicin Salicyl alcohol Amines.-The lower members of the aliphatic amines (like methylamine) are flammable gases, with an odor resembling ammonia; the higher members (like butylamine) are liquids. With acids they form salts, soluble in water and in alcohol. The aromatic amines are either liquids (like aniline) or solids (like diphenylamine). With aliphatic amines, nitrous acid converts the primary amine into the corresponding alcohol: R.NH2 + HONO -- R OH + N2 + H20 the secondary amine is converted into the yellow nitrosoamine: R2NH + HONO -- R2N-NO + H20 and the tertiary amine is not acted upon. With the aromatic amines, the manner in which nitrous acid behaves will be dependent upon whether the NH2 group is in the nucleus or in the side-chain. If the amino group is in the nucleus, diazonium salts are formed (in the cold) which are converted to phenols on heating; if the NH2 group is in the side-chain, then the compound behaves like an aliphatic amine. With secondary aromatic amines, nitrous acid yields nitroso derivatives similar to those obtained with aliphatic secondary amines. A tertiary amine such as dimethylaniline reacts with HONO to produce p-nitrosodimethylaniline. The primary amines, whether aromatic or aliphatic, give the carbylamine reaction (the isocyanide is formed which has a dis- gusting odor); e.g., 0NH2 0N_C + CHCl3 + 3KOH + 3KCl + 3H20 Nitro compounds.-Only the aromatic nitro compounds are of importance. Usually, these are oily liquids or solids, insoluble in water and dilute HC1. They are identified by being reduced to the corresponding amines; e.g., -NO2 + 3H2 -NH2 + 2H20 Cyanides and Isocyanides.-The cyanides are liquids or solids with an agreeable odor. They are hydrolyzed to the correspond- ing acids; e.g., CH3CN + 2H20 -4 CH3COOH + NH3 and are reduced to the primary amines; e.g., CH3 CN + 4H --> CH3 CH2 NH2 The isocyanides or carbylamines possess a disgusting odor. On hydrolysis, they yield formic acid and an amine; e.g. CH3 N==C + 2H20 -> CH3-NH2 + H-COOH Azo compounds.-These are colored solids and include a large class of important dyes. They yield, on reduction, amino compounds; e.g., -N=0N- 4H -NH2 Ao-->ben Azobenzene AZO COMPOUNDS 333 334 THE IDENTIFICATION OF ORGANIC COMPOUNDS Purines, of which uric acid and caffeine are examples, are not easily identified. Most of them give the muroxide test (evaporate the substance on a water bath to dryness with cone. HN03, cool and make alkaline with ammonia or NaOH; a violet or red color is produced). Alkaloids.-These are mostly solids (nicotine, and coniine are exceptions), soluble in alcohol, somewhat less soluble in ether, chloroform and benzene, and usually ; soluble in water. Most of them are levorotatory. They dissolve in acids, forming salts, and are reprecipitated by alkalies. Alkaloids are not easily identified, but as a class they are precipitated by the "alkaloidal reagents," such as tungstic, phosphomolybdic, tannic and picric acids, potassium-mercuric iodide, etc. Many of them are identified by color reactions with H2S04 and an oxidizing agent. Sulfur compounds.-The sulfonic acids have already been treated. The only others that need be mentioned here are the mercaptans (e.g., C2H5SH) and the sulfides (e.g., (C2H5)2S). Both types of compounds have very disagreeable odors. Terpenes and allied compounds.-These substances are flammable, mostly volatile, possess characteristic odors and are insoluble in water, but soluble in many organic solvents. They do not belong to the aliphatic or to the aromatic series of com- pounds and are, as a rule, complex in structure. Certain deriva- tives are usually prepared in order to identify them. Proteins.-These are complex substances consisting, in the main, of linkages of amino acids. They are identified by a number of color tests. With the Millon's reagent (mercuric nitrate containing nitrous acid) most of them give a red color or precipitate. When heated with HN03 a yellow color is developed and this is changed to an orange on the addition of ammonia (xanthoproteic reaction). When mixed with a strong solution of KOH and a drop or two of CuS04 is added, a violet color is obtained (biuret reaction). READING REFERENCES NOYES AND MULLIKEN-Laboratory Experiments on the Class Reactions and Identification of Organic Substances. WESTON-A Scheme for the Detection of the More Common Classes of Carbon Compounds. MEYER AND TINGLE-Determination of Radicals in Carbon Compounds. KINGSCOTT AND KNIGHT--Methods of Quantitative Organic Analysis. MULLIKEN-A Method for the Identification of Pure Organic Compounds. CHAPTER XXXV PLANT AND ANIMAL PIGMENT CHLOROPHYLL, CAROTIN, XANTHOPHYLL, FLAVONES, ANTHO- CYANINS, HEMOGLOBIN AND BILE PIGMENTS Chlorophyll.-The chemistry of chlorophyll, the green pigment in plants, has been worked out by Willstitter and his pupils. Without going into any details, some of the essential points as to its structure and general characteristics may be given. Chlorophyll is really a mixture of two substances: /COOC2oH39 COOC20H39 MgC31H29N3-COOCH3 MgC32H28O2N4 H CO COOCH3 HN Chlorophyll a Chlorophyll b Both contain the element magnesium in organic combination, and both are esters of a tribasic acid, chlorophyllin, combined with phytol, C20H390H (an unsaturated alcohol) and methanol. With alkali the ester groups in chlorophyll are hydrolyzed, giving the corresponding carboxylic acids (chlorophyllins). The COOH groups can next be removed by heating with alkali. Acids (oxalic or HC1) remove the magnesium from the molecule; e.g., COOC20H39 C00C2oH39 MgC32H2802N4 - C32H3002N4/ COOCH3 COOCH3 Chlorophyll b Pheophytin b When chlorophyll a or chlorophyll b is oxidized, we get, among CH3 . C-CO other products, methyl ethyl maleinimide >NH C2H5 -C-CO 335 PLANT AND ANIMAL PIGMENTS CH3 - C-CO and hematinic acid >NH, products which HOOC -CH2- CH2 -C-CO are formed in the oxidation of hemoglobin. Carotin is associated with chlorophyll in the green leaf. It is a hydrocarbon with the formula C40H56. Xanthophyll, also associated with chlorophyll (and carotin), has the formula C40H502. By oxidation, xanthophyll may be obtained from carotin, and vice versa by reduction, xanthophyll yields carotin. It is assumed that both these pigments play an important rble in plant respiration. (Pigments from the egg yolk and blood serum have been isolated which are identical with. carotin and xanthophyll.) Flavones.-A number of yellow substances derived from flavone occur in plants 22' Some of these are chrysin (1, 3-dihydroxyflavone) which occurs in several varieties of poplar; apigenin (1, 3, 4'-trihydroxyflavone) HO- \_D-OH I CO OH found in parsley and celery in the form of glucosides; etc. Anthocyanins are red, violet and blue pigments present in flowers, fruits, leaves of plants, etc., in the form of glucosides. By hydrolysis, the anthocyanins are converted into glucose (or other monosaccharide) and anthocyanidins. It is believed that these anthocyanins are reduction products of flavones (and vice versa, that flavones are oxidation products of anthocyanins), and that changes from one to the other are brought about in the plant by oxidizing and reducing enzymes. 336 HEMOGLOBIN The anthocyanin in the cornflower and the rose is known as "cyanin," and this, on hydrolysis, yields two molecules of glucose and cyanidin (an anthocyanidin): OH Cyanidin This cyanidin, Willstitter has also a hydroxyflavone: obtained by reducing quercitin, OH Quercitin or 1, 3, 3', 4'-tetrahydroxyflavonol Hemoglobin, the red pigment in blood, is a combination of hematin, an iron-containing substance, and globin, a protein belonging to the group of histones. It forms compounds with oxygen and carbon monoxide, forming oxyhemoglobin and car- boxy-hemoglobin, the latter being the more stable. "Hemin " (or "hematin hydrochloride ") is obtained from dried blood by boiling with glacial acetic acid. Very characteristic dark plates and prisms are obtained, which may be identified under the microscope. This method is made use of for the detection of blood. When hemoglobin is treated with H2S04, the iron is set free as ferrous sulfate and hemotoporphyrin, an iron-free hematin, is obtained. From this substance, hemopyrrole, CH3-C-C--C2H5 CH3-C CH NH 337 PROPERTIES OF PARAFFINS (The sodium acetate is the sodium salt of acetic acid, CH3 -COOH. The latter, in turn, may be regarded as methane, CH4, having one of its hydrogens replaced by the COOH group, known as the " carboxyl " group. See p. 79.) Properties.-It is a colorless gas with a slight odor, and burns with an almost non-luminous flame: CH4+202 -- C02+2H20 Methane has high fuel value. If mixed with air and ignited, it explodes; this explains many explosions in coal mines (" fire- damp "). The chemical properties of methane apply to the entire group of saturated hydrocarbons (p. 26) of which methane is the first member. Methane is an inactive and stable compound. (Methane and other hydrocarbons of this series are known as paraffins, which means " little affinity.") The common reagents, such as hydro- chloric, nitric, sulfuric and chromic acids, and sodium and potas- sium hydroxides, do not react with it. On the other hand, the halogens, such as chlorine and bromine, react rather vigorously with methane, particularly in the presence of sunlight: H H-C- H + C1 Cl H H Cl Cl I + H-C- H Cl Cl1 H H Cl _ + Cl 1H -C- H Cl H -- H-C--CI+HCI H (CH3Cl) Cl C1 -* H-C-C1+2Hi H (CH2C2) Cl -- Cl-C--C11-3HCI H (CHC13) PLANT AND ANIMAL PIGMENTS may be obtained-a substance, which is also a decomposition product obtained from chlorophyll. Bile pigments (bilirubin, biliverdin, bilicyanin, etc.) are the substances which are responsible for the characteristic color of bile. They are formdd in the liver and originate from the hemo- globin of the blood. Bilirubin, C32H36N406, a reddish-brown pigment, found in abundance in carnivora, is oxidized (even by the oxygen of the air) to biliverdin, C32H3GN408s, a green pigment, found largely in the bile of herbivora. (Hydrobilirubin, a reduced product of bilirubin, is probably isomeric with stercobilin, the pigment of the feces, and with urobilin, a pigment in urine.) The Gmelin's test for bile pigments-the play of colors obtained when cone. HNO3 is added to bile-is dependent upon the pro- duction of various colored oxidation products of the type of bilirubin, biliverdin, etc. Melanins.-This group includes several different varieties of amorphous black or brown pigments which are insoluble in water, alcohol, ether, chloroform, dilute acids, and which occur in skin, hair, etc. They are said to be derived from the amino acids tyrosine (p. 142) and tryptophan (p. 317). READING REFERENCES PALMER-Carotinoids and Related Pigments. WILLSTXTTER-Chlorophyll. Journal of the American Chemical Society, 37, 323 (1915). HARROw-Plant Pigments: Their Color and Interrelationships. Bio- chemical Bulletin, 4, 161 (1915). 338 CHAPTER XXXVI ENZYMES, VITAMINS, HORMONES EJNZYMES THESE are catalytic substances produced as a result of cellular activity. They are responsible for many of the chemical changes which occur in the body. So far enzymes have not been isolated in the pure condition, but they can be classified because they are "specific " in their action; that is to say, ptyalin, the enzyme found in saliva, will act on starch and one or two other carbohydrates, but not on proteins, whereas pepsin, the enzyme found in the gastric juice of the stomach, will act on proteins but not on carbohydrates. A few of the common enzymes, giving their distribution, the substances acted upon ("substrates ") and the end products formed, are given on the following page. The ending ase has been adopted to denote an enzyme; for example, sucrase is an enzyme, its name also suggesting that it acts on the sugar sucrose. However, old names, such as pepsin, trypsin and rennin, still remain. Enzymes are soluble in water, dilute salt solutions, dilute alcohol and glycerol. Like the proteins, they are precipitated by ammonium sulfate and concentrated alcohol. They are very easily. adsorbed by various substances and show colloidal prop- erties. They are, as a rule, destroyed at the temperature of boiling water, and their action is inhibited, but not destroyed at 0 0C. The enzymes act best (or show an optimum activity) around 37-450 C. Enzymes are extremely susceptible to changes in hydrogen ion concentrations, and for each enzyme there is a particular PH at which its reactivity is at a maximum ("optimum reaction "). For example, the pa of trypsin is 8.0, that of pepsin 1.4, and of ptyalin 6.7. Since the neutral point is pa 7, this means that trypsin acts best in an alkaline solution, whereas pepsin acts 339 ENZYMES, VITAMINS, HORMONES best in a decidedly acid solution, and ptyalin is most reactive in a slightly acid medium. Distribution Name and Class Ptyalin Lactase Maltase Sucrase or invertase Zymase Urease Steapsin or lipase Catalase . Peroxidase Erepsin Rennin Thrombin Trypsin Pepsin Micrococcus ure bean, etc. Pancreatic juice Plant and anir sues Plant and anir sues Substrate Starch, dextrin, etc. Lactose Maltose Sucrose Sugars ae, soy Urea Fats nal tis- Hydrogen peroxide nal tis- Organic peroxides Intestinal mucosa and juice, other tissues Gastric juice Blood Pancreatic juice Gastric juice Peptids, also pep- tones and casein Casein Fibrinogen Proteins Proteins Saliva Intestinal juice and mucosa Blood serum, liver, saliva, pancreatic and intestinal juices and lymph Intestinal juice and mucosa Yeast VITAMINS It has recently been found that besides proteins, fats, carbo- hydrates and mineral salts, there are other, as yet, ill-defined substances which, though needed in but minute quantities, are essential to life. These substances are known as vitamins. At End-products Maltose Glucose and galactose Glucose Glucose and fructose Alcohol, CO2, etc. Carbon dioxide and ammonia Fatty acid and glycerol Oxygen or oxi- dation prod- ucts Oxygen or oxi- dation prod- ucts Simpler peptids and amino acids Paracascin Fibrin Proteoses, pep- tones, peptids, amino aOcids Proteoses,/ pep- tones, and peptids 340 VITAMINS least three well-defined vitamins have been detected, though there is persistent talk of a possible fourth. For purposes of identifi- cation, the vitamins are often called "fat-soluble A," "water- soluble B," and "water-soluble C," (or vitamins A, B, and C). The presence of all three of these vitamins is essential to well- being. As a matter of fact, very few foods contain all three. Milk is one of the rare exceptions, but even then the quantity of vitamin C, which it contains is dangerously small. It is only by eating a variety of foods that we assure ourselves a liberal allow- ance of all three types of vitamins. Fat-soluble A.-This is present in abundance in milk, butter, egg-yolk, cod-liver .oil, and to a lesser extent, in beef fat and in many vegetable foods (lettuce, spinach, cabbage, carrots, pota- toes, etc.). Lard and vegetable oils, such as olive oil are practic- ally devoid of it. Cereals in general (wheat, rye, barley, etc.) contain little. In a general way, the statement may be made that this vitamin is present in green leaves and in the embryos of many seeds. Water-soluble B.-This is more abundant than either of the other two. In fact, nearly all natural foods contain some of it. Yeast is particularly rich in this vitamin; so are milk and orange juice. The cereals contain it but only the outer layers, so that in patent flour there is much less of this vitamin than in whole wheat flour. Water-soluble C.-Most fresh fruits and fresh vegetables con- tain this vitamin. The emphasis is advisedly put on fresh material. The orange and the tomato are particularly good examples. Effect of heat and oxidation.-All three vitamins are more or less susceptible to heat, so that any process involving this opera- tion-cooking or canning-is apt to destroy, or greatly lessen, the efficacy of the vitamins. The general experience has been that heating for a long time at a comparatively low temperature is even more harmful than heating for a short time at a compara- tively high temperature. Of the three, the vitamin .C seems the most susceptible to heat and the vitamin B least susceptible. The activity of all three vitamins is lessened by exposure to air or oxidation. This is particularly true of vitamins A and C. Diseases due to lack of vitamins.-Three diseases have been identified as being due to vitamin deficiency. One of them is 341 ENZYMES, VITAMINS, HORMONES beri-beri, involving a general paralysis of the system and is due to a lack of vitamin B; another is scurvy, involving choppy gums and loose teeth and is due.to lack of vitamin C; and the third is xerophthalmia, an eye disease, involving a lack of vitamin A. (Rickets, at one time supposed to be due to a lack of vitamin A, has a more complex origin.) HORMONES In the body there are various ductless glands (glands without tubes), such as the thyroid, the pituitary, the adrenals, etc., which manufacture specific substances that find their way into the blood stream and influence other organs of the body. The substances so manufactured are called "hormones" (from the Greek "to excite") or "chemical messengers." These hormones profoundly influence various activities of the body. In at least two instances hormones have been-isolated in the pure condition, Adrenaline.-One of the hormones of the adrenal glands. may be isolated from the latter by first treating concentrated adrenal extracts with alcohol, lead acetate, etc.; then precipitat- ing the active substance by the addition of concentrated ammonia. The precipitate is purified by repeatedly dissolving in acid and reprecipitating with ammonia. The adrenaline may be synthe- sized by the following reactions: HO- 0 + CH2CI COC1 -- HO- U Chloroacetyl chloride Catechol HO- -CO.CH2C1 + CH3 NINH2 HO- Chloroacetyl catechol HO- CO-CH2-NH-CH3 + H2 HO- __---) OH- -CHOH CH2. NH-CH3 OH d Adrenaline 342 READING REFERENCES Adrenaline is most frequently used to constrict the blood vessels and thereby increase the blood pressure. It is by far the most powerful known hemostatic (checks bleeding). Thyroxin is the hormone in the .thyroid gland. Kendall, who has isolated it from the gland, has given it the formula I H H \/ S4--=--C-CH2-CH2-COOH 2\OH H 4, 5, 6-Trihydro-4, 5, 6-triiodo-2-hydroxy--indolepropionic acid. It is administered in diseases involving a deficient secretion of the thyroid gland. Insulin.-This is the hormone present in the pancreas, and its absence, as Banting and Macleod have recently shown, gives rise to diabetes. Insulin has not, as yet, been isolated in the pure state, but some very active extracts are obtainable. An extract containing insulin is now universally used in the treatment of diabetes. The extract has to be injected. Pituitrin, an impure extract of the pituitary body, which contains the hormone, is used to promote uterine contractions and to stimulate peristalsis. Secretin represents a hormone present in the intestinal mucosa which plays an important part in controlling the flow of pancreat,ic juice into the small intestine, and thereby aids in digestion READING REFERENCES BAYLIss-The Nature of Enzyme Action. BARGER-The Simpler Natural Bases. (1914), pp. 81-101 (Adrenaline). FALK-The Chemistry of Enzyme Actions. HARRow-Contemporary Science. (1921), pp. 76-84 (What Are Enzymes?) HARRow-Vitamins-Essential Food Factors. SHERMAN AND SMITH-The Vitamins. HARRow-Glands in Health and Disease. 343 CHAPTER XXXVII NOMENCLATURE OF ORGANIC COMPOUNDS THE number of organic compounds is in excess of 225,000, and the naming of such compounds presents no little difficulty. Some of the methods adopted for naming organic compounds have been referred to in the various chapters of the book. In the present chapter, the methods adopted will be briefly sum- marized. In addition, the naming of various groups, and the principles involved in the naming of a number of somewhat complex compounds, will be given. It is hoped that such an outline will prove of value to the student of chemistry who is about to begin more advanced work in organic chemistry, or in one of its many applications, and who will have occasion to con- sult the standard reference books and the current literature. It would be well, at the outset, for the student to review the chart at the beginning of the book, which gives type formulas. From this chart, as well as from various chapters in the book, we may deduce the following rules: A word ending in -ane -ene or -ylene -ine -diene -diine -ene -ol -diol -al -one -ic (sometimes -oic) -ase -ose -ate, -ite Indicates paraffin olefin acetylene diolefin diacetylene aromatic hydrocarbon (as ar ) hydroxyl group two hydroxyl groups aldehyde ketone (or quinone) acid enzyme sugars salts, esters 344 NOMENCLATURE OF ORGANIC COMPOUNDS In naming1 a compound so as to indicate that oxygen is replaced by sulfur, the prefix thio is used; e.g., HCNS, thiocyanic acid; CS(NH2)2, thiourea. Hydroxyl derivatives of hydrocarbons end in -ol, as glycerol, resorcinol, pyrocatechol. The names of the groups NH2, NHR, NR2, NH or NR end in -ido only when they are substituents in an acid group, otherwise in -ino; e.g., CH3 C=NH, ethyl imidoacetate; CH2 -CH2 COOH, OC2H5 NH2 0-aminopropionic acid. Hydroxy is used to designate the hydroxyl group; e.g., CH2. COOH, hydroxyacetic acid. OH Salts of organic bases with hydrochloric acid are called hydro- chlorides; e.g., / NH2 - HCl, aniline hydrochloride. Compounds which are not alcohols, but have received names ending in -ol are spelled -ole, as anisole, indole. C6H6 is called benzene (not benzol), C7Hs toluene, etc. The endings -ine are used for basic substances, and -in for glycerides, glucosides, bitter principles, proteins, etc.; e.g., aniline, purine, morphine; but gelatin, palmitin, amygdalin, albumin, protein. In naming organic compounds the connective o is used in such names of substituent radicals as amino-, bromo-, cyano-, and iodo-; e.g., bromobenzene, chloroacetic acid, nitroaniline. Acid radicals, such as CrH5CO, end in -yl, and their compounds with halogens, as C6H5COC1, are called chlorides, bromides, etc.; e.g., benzoyl chloride. The names butane, pentane, etc., are used only for the normal hydrocarbons, with the prefix cyclo-, for saturated cyclic hydro- carbons. To designate ortho-, meta-, para-, dextro-, levo-, racemic, symmetrical, secondary, tertiary and meso, we use o-, m-, p-, d-, l-, dl-, sym-, sec-, tert- and meso-, respectively. 1These suggestions are taken from the publications of the American Chemical Society. 345 346 NOMENCLATURE OF ORGANIC COMPOUNDS Numerals precede the part of the name to which they refer; e.g., 2-bromo-3-methylbenzenesulfonic acid. For complex cyclic compounds requiring fixed numberings, the student is referred to Richter's Lexikon der Kohlenstoff- Verbindungen, Vol. 1. The following list gives the names of a number of important organic radicals: 2 acetamido CH3CONH- acetenyl = ethinyl acetimido CH3C(: NH)- acetonyl CH3COCH2- acetoxy CH3CO 0-- acetyl CH3CO- acetylene = CH - CH= acrylyl CH2 : CHCO- adipyl -OC (CH2)4 - CO- alanyl CH3. -CHNH2 - CO- alkoxy RO-(any alkyl radical attached by oxygen) allyl CH2 : CH - CH2- p-allyl = isopropenyl amidoxalyl H2N. CO - CO- amino (amido) H2N- amoxy CH3- (CH2)4 0- amyl CH3- (CH2)4- or C5H1l CH3CH2 tert-amyl (CH3)2 (CH3)2/ amylidene CHa3 (CH2)3. CH= anilino C6H5NH- anisal p-CH30 C6H4. CH= anisoyl p-CH30 - C6H4- CO- anisyl (o, m or p) CHa30 C6H4- anisylidene = anisal CO anthranilo o-CeH4 I \N- anthranoyl o-H2N C6H4 - CO-. anthraquinonyl (from anthraquinone, 2 isomers) anthryl (from anthracene, 5 isomers) 2 The list is taken from one prepared by the editors of Chemical Abstracts or the "Decennial Index" and brought up to date in subsequent editions. NOMENCLATURE OF ORGANIC COMPOUNDS anthrylene (from anthracene, 11 isomers) antipyryl (from antipyrine) OC. N(C6H5) N(CH3) C(CH3): C- 51 2 3 4 arseno -As=As- arsino (from arsinic acid) (OH)OAs- arsinoso 0 : As- arsono (from arsonic acid) (HO)2OAs- arsylene HAs: asaryl 2,4,5-(CH30)3. CGH2- asparagyl H2N CO. CH2 CHNH2 - CO- aspartyl -CO - CH2. CHNH2 - CO- auro Au- azido = triazo azimino (azimido) -N : N NH- azino =-N- N azo -N : N- azoxy --N 0 N- benzal CoH5 CH= benzamido C6H5. CONH- benzenyl C6H5. C= benzilyl Ph2C(OH)CO- benzidino (from benzidine) H2N. CG6H C6H4. NH- benzimido C6H,. C(: NH)- benzohydryl (C6H)2CH- benzohydrylidene = diphenylmethylene benzoxy C6H5 COO- benzoyl C6H5, CO- benzoylene --CH4. CO- benzyl C6H5- CH2- benzylidene = benzal biphenylene -C6H4" C6H4- biphenylenedisazo -N : N C6H4 C6H4 N : N- bornyl (from borneol) 7 F--C(CH3)2--- CH2 CH - CH2. CH2. C(CH3) CH- 3 4 5 6 1 2 347 20 SATURATED HYDROCARBONS OR PARAFFINS IH C1 C1 C1 I I cl I1H]-C- Cl Cl >C1l-C-C1+4HCI I + 1 IH Cl C1 Cl (CCl4) You will notice, in these examples, that the chlorine replaces the hydrogen in the molecule. Whenever an element or a group of elements replaces another element or group of elements in a compound, the process is known as " substitution." Such reac- tions are characteristic of saturated hydrocarbons. CH3C1, CH2C12, CHC13 and CC14 are chlorine substitution products of methane. CH3Cl = methyl chloride or monochloromethane; (CH3= methyl group) (monovalent). CH2C12 = methylene chloride or dichloromethane; (CH2 = methylene group) (divalent); CHCl3 = trichloromethane or chloroform. CC14 = tetrachloromethane or carbon tetrachloride. (Many of these names need not be memorized. If the student will but remember that these compounds are substitution products of methane, he will have little difficulty in naming them. In CH3C1, for example, the compound may logically be regarded as methane in which one of the hydrogen atoms has been replaced by chlorine; hence the name " monochloromethane." But it must also be remembered that the CH3 group is known as a " methyl " group; hence also the name " methyl chloride.") Ethane, C2H6. This is the second member of the paraffin series, and in its general physical and chemical properties shows resemblances to methane. It is found in natural gas and petro- leum. Its formula is represented by H H H-C-C-H H H 348 NOMENCLATURE OF ORGANIC COMPOUNDS borylO : B- bromo Br- A'-butenyl CH3CH2CH : CH- A2-butenyl CH3 - CH : CH - CH2- A3-butenyl CH2 : CH (CH2)2- butoxy CH3 (CH2)3 0- butyl CH3(CH2)3- CH3CH2\ sec-butyl CH3C H- CH3/ tert-butyl (CH3)3C- butylene -CH2 CH2 - CH2 - CH2- [1,4-form] butylidene CH3- (CH2)2. CH= butyryl CH3. (CH2)2 - CO- camphanyl (from camphane) CloH17 camphoroyl (from camphoric acid) CsH14(CO)2: camphoryl (from camphor) CloH50- camphorylidene (from camphor) CloH140: carbamido H2N -CO. NH-- carbamyl H2N- CO- carbanilino = phenylcarbamyl carbazyl (from carbazole, 5 isomers) C12HsN- carbethoxy C2H50 OC- carbomethoxy CH30 OC- carbonyl OC= carbonyldioxy -0 - CO - 0- carboxy HO - OC- (4) (CH3)2CH carvacryl (CoH.--(2) (1) CH3/ cetyl CH3(CH2)14CH2- chloro Cl- chloromercuri C1Hg- cinnamal C6H5- CH : CH- CH= cinnamenyl = styryl cinnamyl C6H5CH : CHCO- cinnamylidene = cinnamal cresotyl (from cresotic acid) 2, 3-(OH)(CH3)C6H3CO)- cresoxy = toloxy cresyl (10 isomers) (o, m or p) (HO) (CH3) C6H3- cresylene = tolylene NOMENCLATURE OF ORGANIC COMPOUNDS crotonyl CH3CH : CHCO- cumal p-(CHa)2CH . C6H4 CH= cumenyl (CH3)2 -CH. C6H4- cuminal = cumal cyano NC- cyclobutyl CH2 CH2 CH2. CH- cyclohexenyl (from cyclohexene, 3 isomers) CoHj-- cyclohexyl (from cyclohexane) C6HI1- cyclohexylidene CH2 C CH2 CH2 CH2 C C cyclopentenyl (from cyclopentene) C5H7- cyclopentyl (from cyclopentane) C5H-- cyclopropyl CH2 CH2 - CH- (4) (CH3)2CH cymyl (1)CH3C6H3-(3) (1) CH/ desyl CH- C6H5.CO/ diazo -N : N- diazoamino = azimino diazo6xy -N(: 0): N- epoxy -0- (to different atoms already united in some other way) ethene = ethylene ethenyl CH3C-- ethinyl CH i C- ethoxalyl C2H50- OC. CO- ethoxy C2H50- ethyl CH3CH2- ethylene -CH2 - CH2- ethylenedioxy -0 - (CH2)2 0- ethylidene CH3CH= fluoro F- fluorylidene (from fluorene) C13Hs : fluoryl (from fluorene, 5 isomers) C13H9- formamido HCONH- C6H5sN : N formazyl C - C6H5. NH N - formyl OCH- 349 350 NOMENCLATURE OF ORGANIC COMPOUNDS fural (2 isomers). - CH : CH CH : C CH= furfural = fural furfuryl= furyl furfurylidene = fural furoyl OCH : CH CH : C- CO- furyl (2 isomers) O CH : CH CH : C- furylidene = fural geranyl (from geraniol) C1oH17- glutamyl -OC - CHNH2 - (CH2)2 CO- glutaryl -OC (CH2)3 CO- glyceryl -CH2 CH - CH2- glycolyl HOCH2 - CO- glycyl H2NCH2 - CO- glyoxyl OCH - CO- guaiacyl = o-anisyl guanido H2N C(: NH) NH- guanyl H2N. C(: NH)- hendecyl CH3. (CH2)10- heptyl CH3- (CH2) 6- hexadecyl = cetyl hexyl CH3 (CH2)5- hippuryl PhCONHCH2CO- homopiperonyl (3,4) (CH202) ' C6H3. CH2 CH2- NH hydrazi I (to same atom) hydrazino H2N.NH- hydrazo -HN. NH- (to different atoms) hydrazono H2N- N= hydroxamino HONH- hydroximino = isonitroso hydroxy (hydroxyl) HO- -idene added to any radical usually means a double bond at point of attachment imidazolyl (from imidazole, 4 isomers) C3H3N2- imino (imido) NH= indenyl (from indene, 7 isomers) CHs8- NOMENCLATURE OF ORGANIC COMPOUNDS indyl (from indole, 7 isomers) CsH6N- indylidene (from indole) CsH7N : iodo I- iodoso OI- iodoxy 021I- isoallyl = propenyl isoamoxy (CH.3)2. CH. CH2 -CH20- isoamyl (CH3)2 CH-CH2 CH2- isoamylidene (CH3)2 CH CH2 . CH= isobutenyl (CH3)2 C OCH- isobutoxy (CH3)2. CH. CH20- isobutyl (CH3)2CH. CH2- isobutyryl (CH3)2. CH. CO- isocyano C : N- N isodiazo I (to some atom) HN/ isohexyl (CH3)2 - CH - (CH2)3- isoindyl (from isoindole, 4 isomers) CsH8-N- isoleucyl CH3. CH2 . CH(CH3). CHNH2 - C0- isonitro HOON= isonitroso HON= A2-isopentenyl (CH3)2 . CH - CH : CH- isophthalal (m) = HC C6H4. CH== isophthalylidene = isophthalal isopropenyl CH3 C- CH2'/ isopropoxy (CH3)2 CHO- isopropyl (CH3)2 - CH- isopropylidene (CH3)2. C- isoquinolyl (from isoquinoline, 9 isomers) CgHoIN- isothiocyano S : C : N- isovaleryl (CH3)2 - CH - CH2 - CO- isoxazolyl (from isoxazole, 5 isomers) C3H20N- keto 0= (to same atom) leucyl (CH3)2 CH' CH2 - CHNH2 - CO- malonyl -OC - CH2 - CO- menthyl (from menthane) CH3 - CH. (CH2)2 - CH(i-C3H7) - CH2 - CH- 351 352 NOMENCLATURE OF ORGANIC COMPOUNDS mercapto HS- mercuri HHg- or -Hg- mesityl (from mesitylene) 3,5-(CH3)2C6H3CH2- methene = methylene methenyl CH= methionyl -S02CH2S02- methoxy CH30- methyl CH3- methylene CH2= methylenedioxy -0 -0. CH2 O- methylol = (hydroxymethyl) naphthal CloH7CH= naphthalimido (from naphthalic acid) C1oH6(CO)2N- naphthenyl C1oH7C- naphthobenzyl Cl0H7CH2- naphthoxy CloH70- naphthoyl CloH7CO- naphthyl (1- or 2-) C1oH7- naphthylene CoH6=-- naphthylidene CloHs : nitramino 02N NH- nitrilo NF nitro 02N- aci-nitro = isonitro nitroso ON- octyl CH3 -(CH2)7- oxalyl -OC CO- oxamido H2N CO - CONH- oximido = isonitroso oxy -0- (used as a connective; cf. epoxy and keto) pentamethylene -CH2(CH2)3CH2- pentazido N=N-N=N-N- pentenyl (like butenyl) pentyl = amyl perimidyl (from perimidine, 8 isomers) CilH7N2- perthio (replacing 0 only) S : S- phenacyl C6H5- CO. -CH2- phenacylidene PhCOCH : phenanthryl (from phenanthrene, 9 isomers) C14H9- 353 NOMENCLATURE OF ORGANIC COMPOUNDS phenanthrylene (from phenanthrene) C14H8 : phenethyl C6H5- CH2CH2- phenetido C2H50. C6H4 NH- phenetyl (o, m or p) C2H50 C6H4- phenoxy CGHs0- phenyl C6H5- phenylazo C6H -N : N- phenylcarbamido CHs. NHCONH- phenylene (o, or p) C6H4= phenylenedisazo -N : NC6H4N : N- phenylidene (o or p) CH : CH CH2- CH : CH. C phenylureido = phenylcarbamido phosphazo -N : P- phthalal =CH-. CH4 -CH= (o) phthalamido (o) H02C C6H4 CONH- phthalidene (from phthalide) C6H4 C o phthalimido (o) C6H4(CO)2N- phthalyl -OC - COH4 CO- (o) picryl (2,4,6)(N02)3. C6H2- piperidyl (from piperidine, 4 isomers) C5H1oN- piperonyl (3,4) (CH202) C6H3 CH2- piperonylidene (3, 4) (CH202) C6H3 CH= pivalyl (from pivalic acid) (CH3)3CCO- 7 prolyl (from proline) NH- CH2. CH2 CH2 - CH- CO- propargyl HC ! C-CH2- propenyl CH3 CH : CH- propenylidene CH3CH : C : propiolyl HC C.-CO- propionyl CH3 - CH2 - CO- propoxy CH3 CH2 CH20- propyl (n) CH3 CH2 CH2- propylene -CH(CH3)- CH2- propylidene CH3 CH2 CH= pseudoallyl = isopropenyl s-pseudocumyl (1,3,4) (CH3)3' C6H2- 354 NOMENCLATURE OF ORGANIC COMPOUNDS pseudoindyl (from pseudoindole, 7 isomers) CsH6N- pyrazolyl (from pyrazole, 4 isomers) C3H3N2- pyridyl (from pyridine, 3 isomers) C5H4N- pyrimidyl (from pyrimidine) C4H3N2- pyrroyl CH : CH CH : CH-NCO- pyrryl (from pyrrole, 3 isomers) C4H4N- quinolyl (from quinoline, 7 isomers) C,HN- quinonyl = quinoyl quinoxalyl (from quinoxaline) CsH,N2- salicyl (o) HO - C6H4- salicylal (o) HO C;H4. CH= salicylyl (o) HO C6H4 CO- selenino (HO)O Se- seleno Se= selenocyano NCSe- selenono (OH)2OSe- selenonyl -SeO2- silicono (OH)O Si- silicyl H3Si- silicylene H2Si= stearyl CH3 - (CH2)16. CO- styrene -CH(C6Hs) CH2- styrolene = styrene styryl C6H5 CH : CH- succinamyl H2N. CO - CH2CH2 CO- succinyl -OC - CH2CH2 - CO- sulfamino H03S- NH- sulfamyl H2NO OS- sulfhydryl = mercapto sulfino H02S- sulfinyl OS= sulfo H03S- sulfonamido R -SO2. NH- sulfonyl R S02- sulfuryl = sulfonyl tauryl H2N. CH2CH2SO2- telluro Te= terephthalal (from terephthalaldehyde) :HCCoH4CH : tetramethylene = 1,4-butylene tetrazyl (from tetrazine, 2 isomers) CHN4- NOMENCLATURE OF ORGANIC COMPOUNDS thiazyl (from thia:ole, 3 isomers) CsH2NS- thienyl (from thiophene, 2 isomers) C4H3S- thio -S- thiocarbonyl SC= thiocyano NCS- thiohydroxy = mercapto thiol (S replacing 0 in OH) Used in place of "thio " only thiono (S replacing 0 in CO) when required for distinction thionyl = sulfinyl thujyl (from sabinane, attached at 2 position) C1oH17- thymyl (from thymol) HO C : C(CH3) CH : CH C(i-C3aH) : C- toloxy (o, m or p) CH3 - CoH40- toluino (o, m or p) CH3 - C6H4 - NH- toluyl (o, m or p) CH3 CoH4. CO- a-toluyl C6H5 CH2 - CO- tolyl (o, m and p) CH3 - C6H4- a-tolyl = benzyl tolylene (6 isomers) CH3 CGH3= a-tolylene = benzal triazeno NH2-N : N- triazo N :N. N- triazolyl (from tria:ole) C2H2Na- trimethylene -CH2CH2CH2- tryptophyl (from tryptophan) C11H1102N2- tyrosyl (from tyrosine) p-HO- CH4 -CH2CHNH2 - CO- undecyl= hendecyl (in sense C1IH23-) uramino = carbamido ureido (by some used synonymously with carbamido) -NH CO NH- valeryl CH3- (CH2)3 - CO- valyl (from valine) (CH3)2 -CH. CHNH2 - CO- vanillal (3,4) (CH3O)(HO) - C6H3. CH= vanilloyl (3,4) (CH30)(HO) - C6H3- CO- vanillyl (3,4) (CH30) (HO) - C6H3 CH2- veratral (3,4) (CH30)2- C6H3 - CH veratroyl (3,4) (CH30)2 C6H3 - CO- veratryl (3,4) (CH30)2 - CGH3 CH2- veratrylidene = veratral vinyl H2C : CH- 355 356 NOMENCLATURE OF ORGANIC COMPOUNDS vinylene -CH : CH- vinylidene H2C : C : xanthyl (from xanthene, 6 isomers), C13H90- xyloyl (from xylic acid, 7 isomers) (CH3)2 - C6H3 CO- xylyl (9 isomers) (CH3)2 C6H3- xylylene --H2C C6H114 CH2- We shall now illustrate with a number of examples some of the methods employed in naming compounds: H H H H Br H H I I I I I iI 1. H--C1- C2--C3--C4 C5 C6 7C- H I I I I I I I H H C2H,5 H H CH3 H (a) In naming this compound, first select the longest straight chain. In this case, it would be a seven-carbon chain. There- fore, the naming will center around the saturated hydrocarbon heptane. (b) Consider the elements and groups other than hydrogen as substituents. (c) Therefore the name of this compound becomes: 3-ethyl-6-methyl-5-bromoheptane 1 23 4 2. CH2=C-CH=CH2 CH3 (a) Selecting the longest chain, we have four carbon atoms. (b) Since there are two double bonds in this chain, the name of the compound must end in -diene and center around the unsatu- rated hydrocarbon butadiene. (c) The name of this compound becomes 2-methyl butadiene. (d) But to indicate the positions of the double bonds, the final name becomes 2-methyl-1, 3-butadiene (isoprene). H C N 02N- 62 -N02 SCH NO2 CRH3 NOMENCLATURE OF ORGANIC COMPOUNDS CH (a) This compound contains the benzal 0 (divalent) group wherein the three hydrogens in positions 2, 4, 6, are replaced by three nitro groups. (b) In addition, we have p-toluidine, where in place of the two hydrogens in the amino group, there is a double bond. (c) Therefore, the name of this compound becomes 2, 4, 6-trinitrobenzal-p-toluidine. C12-CH-COOH 4. NH2 OH This compound is named a-amino---p-hydroxyphenylpro- pionic acid (tyrosine), because it has an amino group attached to the a-carbon atom and the p-hydroxyphenyl group attached to the 0-carbon atom. OH NH2 2 5. HO3S- 4 5 4 SO3H This compound is named 1-amino-8-hydroxy-3,6-naphtha- lenedisulfonic acid. ("H-acid ") OH 6. C O H OH 357 ISOMERISM and it differs from methane by CH2. It may be regarded as methane in which one of the hydrogens is replaced by a CH3 group; that is, CH3 CH3, methyl methane, or dimethyl. Further light on the structure of ethane is shed by the way in which it can be synthesized. Methyl iodide reacts with sodium in the following way (Wurtz synthesis): H H H H I II I H-C- II + 2Na + I -C-H - H-C-C-H + 2NaI H H H H In other words, the formation of ethane is here shown to be a coupling of two methyl groups. Isomerism.-Experience has shown that only one mono-sub- stitution product of ethane can be obtained, but it is possible to obtain two di-substitution products, both having the same molecu- lar formula, C2H4C12, but differing from one another in physical and chemical properties. Here we clearly have a case of isomer- ism, and the graphic formulas bear this out: H H H H II - I I H-C-C-Cl H-C-C-Cl I I I I H Cl Cl H (1) (2) for in (1) we see two chlorine atoms attached to the same carbon atom, and in (2) the two chlorine atoms are attached to two dif- ferent carbon atoms. Whenever we have two or more com- pounds having the same molecular formula, but differing in physi- cal and chemical properties, we have an example of isomerism, and the individual compounds are known as isomers. (Let us illus- trate this question of isomerism with an analogy. Suppose we take the figures 4, 7, 5. It obviously makes very much of a dif- ference as to whether we write 475 or 754 or 547. Yet all we have done is to rearrange the figures; and by merely rearranging the numerals we have obtained totally different sums. So it may be with two compounds such as are illustrated above: they may have the same empirical formulas, yet be quite different sub- 358 NOMENCLATURE OF ORGANIC COMPOUNDS This compound is named 1, 4-dihydroxyanthraquinone (quini- zarin.) H H I I SC-C-COOH 7. I 1 SH NH2 N H This compound is named a-amino-3-indolcpropionic acid (Tryptophan). CO H2C6 2CH2 8. H\C H C 0 CNH This compound is named 3,5 - diphenyl- 4 - cyanocyclohexa- none-1. As= As- 9. HgN-O -NH - CH2 - OSONa OH OH This compound is named sodium 3, 3'-diamino-4, 4'-dihydroxy- arsenobenzene-N-methylenesulfinate. APPENDIX GLOSSARY Active principles include carbohydrates, alkaloids, glucosides organic acids, resins, oils and fats, volatile oils, protein bodies and ferments. Analgesics are drugs which relieve pain when absorbed into the blood. Anesthetics are drugs which produce insensibility to pain. (Local anesthetics are drugs which produce insensibility to pain at the site of application.) Anodynes are drugs which relieve pain when applied locally. They are usually milder in action than the analgesics. Antacids are drugs which neutralize acids. Antidote is an agent which affects a poison either physically or chemically or both so as to remove it from the body or alter its character by forming with it an insoluble or inert compound. Antifebrin is another name for acetanilide (used to decrease fever). Antipyretics are drugs which reduce fever. Antiscorbutic is an agent effective against scurvy. Antiseptics are substances which check the growth of bacteria. Antispasmodics are drugs which lessen contractions of muscles, and also lessen convulsions. Aperients are substances which produce mild movements of the bowels. Aromatics are spicy substances which increase the secretion of the stomach and the intestines. Astringents are drugs which contract or harden the tissues. 359 APPENDIX Bactericide is an agent which destroys bacteria. Balsams are semi-fluid, resinous and fragrant vegetable juices of many varieties. Bitters are drugs which increase the appetite because of their bitter taste. Cardiac stimulants are drugs which increase the activity of the heart. Cardiac depressants are drugs which lessen the heart action. Carminatives are drugs which produce a feeling of comfort in the stomach and relieve the formation of gas in the stomach and the intestines. Catabolism is the breaking down of tissue material in the body. Cathartics are drugs which cause movements of the bowels. Caustics are substances which burn or destroy tissues. Counterirritants are drugs which act on the skin. Cyanosis signifies "blueing" of the skin. Deodorants are remedies which destroy unpleasant odors. Disinfectants are drugs which check the growth of bacteria. Diuretics are drugs which increase the flow of urine. Emetics are drugs which produce vomiting. Expectorants are drugs which increase coughing and bronchial secretions. Febrifuges are drugs which reduce fever. Gums are amorphous, transparent substances which are widely disseminated in plants. Hemostatics are substances which check bleeding. Hypnotics are drugs which produce sleep. Lachrymator is a substance which produces the secretion and discharge of tears. Lacteal is any one of the intestinal lymphatics which absorbs fats. Laxatives are drugs which produce mild movements of the bowels. Myotics are drugs which narrow (contract) the pupil of the eye. Mydriatics are drugs which widen (dilate) the pupil of the eye. Narcosis is the state of profound unconsciousness produced by a drug. 360 GLOSSARY Narcotic is a drug which produces stupor or complete insensibility. Parasiticide is an agent which destroys the animal and vegetable parasites found upon the human body. Peristalsis is the worm-like movement by which the alimentary canal propels its contents. Purgatives are drugs which produce moderately active and fre- quent movements of the bowels. Putrefaction is the decomposition of animal or vegetable substances effected largely through micro-organisms, and resulting in the production of various solids, liquids and gases, some of which have a foul odor. Refrigerants are substances which relieve thirst and cool the patient, in fever. Resins are complex bodies of resinous character. They are generally considered to be oxidation products of hydrocarbons such as terpenes. Respiratory stimulants are drugs which increase the depth and frequency of breathing. Respiratory depressants are drugs which lessen the frequency and depth of breathing. Rubefacients are drugs which redden the skin by widening (dilat- ing) the capillaries. Sedatives are drugs which lessen the activity of an organ or part of the body. Somnifacients or Soporifics are drugs which produce sleep. Styptics are substances which stop bleeding. Trypanocidal power is the power possessed by certain bodies of destroying certain parasites found in the blood of man and of animals. Vaso-constrictor is a drug which increases arterial pressure. Vaso-dilator is a drug which lowers arterial tension. Vermicides are drugs which destroy worms. Vertigo means dizziness. Vesicatories or Vesicants are drugs which produce blisters. 361 APPENDIX BOILING AND MELTING POINTS OF A NUMBER OF ORGANIC COMPOUNDS Since very few physical constants are given in the body of the work, we shall here give the boiling and melting points of a number of compounds which the student is apt to encounter. NAME in. p., o C. b. p., o C. Acetaldehyde. ............... Acetam ide ................... Acetanilide................ Acetic acid .................. Acetic anhydride ............. Acetone..................... Acetonitrile. ................. Acetyl chloride. .............. Allyl alcohol. ................ Amyl acetate .............. Aniline...................... Aniline hydrochloride ......... Anthracene.................. Anthraquinone............... Benzaldehyde ................ Rangnela Benzenesulfonic acid............ Benzidine .................... Benzoic acid ................. Butyl alcohol. ................ Camphor ..................... Carbon disulfide ............... Carbon tetrachloride ........... Chloroform. ................... Cinnamic acid ................. Citric acid .................. .. o-Cresol ..................... m-Cresol ..................... p-Cresol .................... .. p-Cymene. .................... Dimethylaniline. ............... Diphenyl ..................... Ethyl acetate .................. Ethyl alcohol .................. Ethyl bromide ................. Ethyl butyrate................ ......... ......... ......... I . . -120 82 114 16.7 - 94 - 45 -129 - 75 - 6.5 198 216 285 - 13.5 5.4 52 127 121 - 79 176 -111 - 23 - 63 133 153 30 11 35 - 73 2 70.5 - 82 -114 -115 - 93 1 For others, consult Olsen-Chemical 362 21 222 305 119 139 55.6 81 55 96 148 184.4 245 360 380 179 80.4 400 249 116 209 46 78 61 300 decomposes 191 202 202 175 194 254 77 78.4 45 120 . . Annual (Van Nostrand). BOILING AND MELTING POINTS NAME m. p., C. Ethyl chloride ............... .......... -140 Ethyl ether .................. ........ -116 Ethyl iodide ............................ -118 Ethylene glycol. ........................ - 17 Formaldehyde ......................................... Formic acid ............ ............. 7.5 Furfural ............................. Glucose ............................ Glycerol................................ Hydrocyanic acid ........................ Iodoform. ........................... Isoamyl alcohol ......................... Isopropyl alcohol ........................ Lactic acid ............................. Methanol.............................. Methyl iodide......................... M ethyl salicylate........................ Naphthalene............................ a-Naphthol............................ -Naphthol ............................ a-Naphthylamine. ........................ p-Naphthylamine...................... Nitrobenzene ........................... O xalic acid ............................. Phenol................................ Phthalic acid ........................... Phthalic anhydride..... ............... Pyridine .............. ................. Pyrogallol. ............................. Resorcinol. ............................. Saccharin............................... Salicylic acid ........................... Sulfanilic acid .......................... Thymol ............................... Toluene............ ................ o-Toluidine............................. mn-Toluidine .......................... p-Toluidine. ............................ Urea.............. ...... ........ Vanillin ................... .......... o-Xylene........................ m-Xylene ............................ p-X ylene............................... b. p., C. 12.5 35 72 199 - 21 100 55 (17 mm.) 291 26 sublimes 131 83 119 (12 mm.) 65 45 222 218 279 285 .300 306 210.8 150 + sub. 182.6 284.5 116 293 280 sub. sub. 231.8 111 199.7 203 200 dec. 285 dec. 144 139 138 363 - 36 146 17 - 10 119 -117 - 85 18 - 95 - 66 - 8 80 96 122 50 111 5 189 45 213 131 - 42 132.5 118 228 dec. 157 288 50 - 93 - 21 - 13 45 132 81 - 27 - 53 15 REFERENCE BOOKS ELEMENTARY ORGANIC TEXTBOOKS BARNETT-Textbook of Organic Chemistry. (Blakiston.) BUNGE-Textbook of Organic Chemistry for Medical Students. (Longmans.) CHAMBERLAIN-Textbook of Organic Chemistry. (Blakiston.) CLARKE-Organic Chemistry. (Longmans.) COHEN-A Class-Book of Organic Chemistry. (Macmillan.) COHEN-Theoretical Organic Chemistry. (Macmillan.) HASKINS-Organic Chemistry. (Wiley.) HOLLEMAN-Textbook of Organic Chemistry. (Wiley.) LOWY AND DOWNEY-Study Questions in Elementary Organic Chemistry. (Van Nostrand.) MOORE-Outlines of Organic Chemistry. (Wiley.) MoUREAU-Fundamental Principles of Organic Chemistry. (Harcourt.) McCoLLuM-Organic Chemistry for Students of Medicine and Biology. (Macmillan.) NoRRIs--Organic Chemistry. (McGraw-Hill.) NoYEs-Organic Chemistry. (Holt.) PERKIN AND KIPPING-Organic Chemistry. (Lippincott.) PORTER-The Carbon Compounds. (Ginn.) REMSEN AND ORNDORFF-Organic Chemistry. (Heath.) SMITH AND SMITH-Chemistry for Dental Students, Vol. II. (Wiley.) STODDARD-Introduction to Organic Chemistry. (Blakiston.) WALKER-Medical Organic Chemistry. (Van Nostrand.) WEsT--Organic Chemistry. (World Book.) Organic Chemistry for Advanced Students ALEXEYEFF AND MATTHEWs-General Principles of Organic Syntheses. (Wiley.) BERNTHSEN-Textbook of Organic Chemistry. (Van Nostrand.) COHEN-Organic Chemistry for Advanced Students. (Longmans.) HENRICH-Theories of Organic Chemistry. (Wiley.) MEYER AND JACOBSON-Lehrbuch der Organischen Chemie. (Veit & Co. Leipzig.) REFERENCE BOOKS POPE --Modern Research in Organic Chemistry. (Van Nostrand.) RICHTER-Organic Chemistry. (Blakiston.) SIDGWICK-Organic Chemistry of Nitrogen. (Oxford.) STEWART-Recent Advances in Organic Chemistry. (Longmans.) Laboratory Books in Organic Chemistry ADAMS, etc.-Organic Syntheses. (Wiley.) BARNETT-Preparation of Organic Compounds. (Blakiston.) COHEN--Practical Organic Chemistry. (Macmillan.) COOK-Laboratory Experiments in Organic Chemistry. (Blakiston.) ELns-Ubungsbeispiele ftir die elektrolytische Darstellung Chemischer Pri- parate. (Knappe, Halle.) FIsHER-Laboratory Manual of Organic Chemistry. (Wiley.) FIscHER-Preparation of Organic Compounds. (Van Nostrand.) GARRETT AND HARDEN-Practical Organic Chemistry. (Longmans.) GATTERMAN-Practical Methods of Organic Chemistry. (Macmillan.) HEIDELBERGER-Advanced Laboratory Manual of Organic Chemistry. (Chemical Catalog.) HOLLEMAN-Laboratory Manual of Organic Chemistry. (Wiley.) HOUBEN AND WEYL-Die Methoden der Organischen Chemie. (Thieme, Leipzig.) JONEs-Laboratory Outline of Organic Chemistry. (Century.) KELLAR-Practical Organic Chemistry. (Oxford.) LAssAR-CoHN-Arbeitsmethoden ftir Organisch-chemische Laboratorien. (Voss, Hamburg.) LAssAR-CoHN-Applications of Some General Reactions to Investigations in Organic Chemistry. (Wiley.) MOORE-Experiments in Organic Chemistry. (Wiley.) NoRms-Experimental Organic Chemistry. (McGraw-Hill.) NoYEs-Organic Chemistry for the Laboratory. (Chemical Publishing.) ORNDORFF-Laboratory Manual in Organic Chemistry. (Heath.) PRICE AND TWIss-Practical Organic Chemistry. (Longmans.) STEEL-Laboratory Manual of Organic Chemistry for Medical Students. (Wiley.) SUDBOROUGH AND JAMEs-Practical Organic Chemistry. (Van Nostrand.) TITHERLEY-A Laboratory Course in Organic Chemistry. (Van Nostrand.) VANINo-Handbuch der Pridparativen Chemie. (Enke, Stuttgart.) WEST-Experimental Organic Chemistry. (Globe Book.) Analytical Books ALEN-Commercial Organic Analysis. (Blakiston.) AUTENRIETH-Detection of Poisons and Powerful Drugs. (Blakiston.) BARNETT AND THORPE-Organic Analysis. (Van Nostrand.) BROWNE-A Handbook of Sugar Analysis. (Wiley.) 366 REFERENCE BOOKS CLARKE-Organic Analysis. (Longmans.) FULLER-Chemistry and Analysis of Drugs and Medicines. (Wiley.) GILL-Oil Analysis. (Lippincott.) GRIFFIN-Technical Methods of Analysis. (McGraw-Hill.) HOLDE AND MUELLER-Examination of Hydrocarbon Oils. (Wiley.) KAMM-Qualitative Organic Analysis. (Wiley.) KINGSCOTT AND KNIGHT-Methods of Quantitative Organic Analysis. (Long- mans.) LEACH-Food Inspection and Analysis. (Wiley.) MEYER AND TINGLE-Determination of Radicles in Carbon Compounds. (Wiley.) MULLIKEN-Identification of Pure Organic Compounds. (Wiley.) NEAVE AND HEILBRON-IdentificationofOrganic Compounds. (Van Nostrand.) NOYES AND MULLIKEN-Identification of Organic Substances. (Chemical Publishing.) SHERMAN-Organic Analysis. (Macmillan.) WESTON-A Scheme for the Detection of the More Common Classes of Carbon Compounds. (Longmans.) WiLEY-Principles and Practice of Agricultural Analysis. (Chemical Pub- lishing.) WINTON-Food Analysis. (Wiley.) Industrial BAILEY-A Textbook of Sanitary and Applied Chemistry.. (Macmillan.) HALE-Modern Chemistry Pure and Applied (Vols. 3,4,5,6). (Van Nostrand.) MRTiN--Industrial and Manufacturing Chemistry, A Practical Treatise. (Appleton.) MoLINAR--Industrial Organic Chemistry. (Appleton.) ROGERs-Industrial Chemistry for the Student and Manufacturer. (Van Nostrand.) SADTLER-Industrial Organic Chemistry. (Lippincott.) SADTLER AND MATos--Industrial Organic Chemistry. (Lippincott.) THORPE-A Dictionary of Applied Chemistry. (Longmans.) THORPE-Outlines of Industrial Chemistry. (Macmillan.) ULLMANN-EnzyklopiLdie der Technische Chemie. (Urban & Schwartzcen- berg, Berlin.) Catalysis EFFRONT AND PRESCOTT-Biochemical Catalysts inLifeandIndustry. (Wiley.) FALK-Catalytic Action. (Chemical Catalog.) HENDERSON-Catalysis in Industrial Chemistry. (Longmans.) JOBLING-Catalysis. (Churchill, London.) RIDEAL AND TAYLOR-Catalysis in Theory and Practice. (Macmillan.) SABATIER AND REID-Catalysis in Organic Chemistry.' (Van Nostrand.) 367 22 SATURATED HYDROCARBONS OR PARAFFINS stances because of the different arrangement of the atoms within the molecule.) Experience has also shown that there are but two tri-, two tetra-, one penta-, and one hexa- substitution products of ethane; and the student can confirm this by studying the graphic for- mulas: H Cl C Cl Cl Cl I I I I I I H-C-C-C1 H-C-C-Cl H-C-C--C H C1 H H H Cl C1 Cl C1 C1 Cl Cl I I I I I I C-C-C-CI C1-C-C-C Cl-c-c-cl H H H Cl C1 C1 In naming substitution products of ethane, the system adopted for methane is used: CH4 CH3 Methane Methyl radical C2HG C2H5 Ethane Ethyl radical C2H5I, for example, is ethyl iodide, or iodoethane, and C2Hs501H is ethyl hydroxide, or hydroxyethane. (The name for the radical corresponding to the hydrocarbon is obtained by changing the suffix-ane into -yl.) Propane, C3Hs.-We have seen that ethane, C2H116, may be regarded as methane, CH4, to which CH2 has been added. Sim- ilarly, propane, C3H8, may be regarded as ethane, C2H16, to which CH2 has been added; or as C2116 in which one of the hydrogens has been replaced by a CH3 group. Its structure becomes evident by examining its synthetic method of preparation. Ethyl iodide and methyl iodide react in the presence of sodium to form propane. The principle was made use of in the synthesis of ethane, and may be made use of in the synthesis of other hydrocarbons. H H H H H H 1H-C- I+2Na+I -C-C--H -- H-C-C-C-H + 2Nal I I I I I I H H H 11 H II REFERENCE BOOKS Bio-chemistry ABERHALDEN-Textbook of Physiological Chemistry. (Wiley.) ARRHENIUS-Quantitative Laws in Biological Chemistry. (Harcourt.) BAYLIss-The Nature of Enzyme Action. (Longmans.) BUNGE-Physiologic and Pathologic Chemistry. (Blakiston.) CATHCART-Physiology of Protein Metabolism. (Longmans.) DAKIN-Oxidation and Reduction in the Animal Body. (Longmans.) EULER-General Chemistry of the Enzymes. (Wiley.) EFFRONT-Enzymes and Their Application. (Wiley.) FALK-The Chemistry of Enzyme Actions. (Chemical Catalog.) HALLIBURTON-The Essentials of Chemical Physiology. (Longmans.) HAMMERSTEN-A Textbook of Physiological Chemistry. (Wiley.) HARRow-Glands in Health and Disease. (Dutton.) HARBEY-The Nature of Animal Light. (Lippincott.) HAWK-Practical Physiological Chemistry. (Blakiston.) MACCLEAN-Lecithin and Allied Substances., (Longmans.) MATHEWs-Physiological Chemistry. (Wood.) MELDOLA-Chemical Synthesis of Vital Products. (Longmans.) PETTIBONE-Physiological Chemistry. (Mosby.) PLIMMER-Practical Organic and Bio-Chemistry. (Longmans.) SALKOWSKI-Laboratory Manual of Physiological and Pathological Chem- istry. (Wiley.) Organic Chemistry in Relation to Medicine BAYLss-Principles of General Physiology. (Longmans.) BLUMGARTEN-Materia Medica for Nurses. (Macmillan.) CLAnRK-Applied Pharmacology. (Blakiston.) CULBRETH-A Manual of Materia Medica and Pharmacology. (Lea & Febiger.) DAKIN AND DUNHAM-Handbook of Disinfectants. (Macmillan.) DORLAND-Medical Dictionary. (Saunders.) FowLER-Introduction to Bacteriological and Enzyme Chemistry. (Lcrg- mans.) FRANCIS, FORTESCUE AND BRICKDALE-The Chemical Bases of Pharmacology. (Arnold, London.) GARRISON-An Introduction to the History of Medicine. (Saunders.) HARRow--Glands in Health and Disease. (Dutton.) KRAEMER-Scientific and Applied Pharmacognosy. (Wiley.) MACLEOD-Physiology and Biochemistry in Modern Medicine. (Mosby.) MAY-The Chemistry of Synthetic Drugs. (Longmans.) McGUIAR-Chemical Pharmacology. (Blakiston.) OSBORNE-Principles of Therapeutics. (Saunders.) OSBORNE AND FISHBEIN-Handbook of Therapy. (Amer. Med. Ass.) 368 REFERENCE BOOKS 369 OSLER-Principles and Practice of Medicine. (Appleton.) PATON-Nervous and Chemical Regulators of Metabolism. (Macmillan.) POTTER-Therapeutics, Materia Medica and Pharmacy. (Blakiston.) REMINGTON-Practice of Pharmacy. (Lippincott.) SPIEGEL-Chemical Constitution and Physiological Action. (Van Nostrand.) STEWART-Handbook of Anaesthetics. (Wood.) TOLLMAN-Manual of Pharmacology. (Saunders.) VINCENT-Internal Secretion and the Ductless Glands. (Longmans.) WELLs-Chemical Pathology. (Saunders.) WITTHAus-Manual of Toxicology. (Wood.) WooD-Chemical and Microscopical Diagnosis. (Appleton.) Organic Chemistry in Relation to Agriculture, Botany, etc. CHAMBERLAIN-Organic Agricultural Chemistry. (Macmillan.) HAAS AND HILL-Chemistry of Plant Products. (Longmans.) INGLE-Elementary Agricultural Chemistry. (Lippincott.) KAHLENBERG AND HART-Chemistry and Its Relation to Daily Life for Students of Agriculture. (Macmillan.) RUSSELL-Soil Condition and Plant Growth. (Longmans.) STODDART-The Chemistry of Agriculture. (Lea & Febiger.) THATCHER AND HART-Chemistry of Plant Life. (McGraw-Hill.) WILEY-Principles and Practice of Agricultural Analysis. (Chemical Pub- lishing.) Organic Chemistry in Relation to Food BAILEY-Food Products, Their Source, Chemistry and Use. (Blakiston.) BAILEY-The Chemistry of Wheat Flour. (Blakiston.) CARTER, HOWE & MAsoN-Nutrition and Clinical Dietetics. (Lea & Febiger.) DOWD AND JAMESON-Food. (Wiley.) EDDY-The Vitamin Manual. (Williams & Wilkins.) ELLIS AND MAcLEOD-Vital Factors of Foods: Vitamines and Nutrition. (Van Nostrand.) FUNK-The Vitamines. (Williams & Wilkins.) GRouT---Chemistry of Bread Making. (Longmans.) HARROW-Vitamines. (Dutton.) HARROW-What to Eat. (Dutton.) HUTCHINSoN-Foods and the Principles of Dietetics. (Wood.) LUsK-Science of Nutrition. (Saunders.) MENDEL-Nutrition. (Yale University Press.) McCOLLOM-Newer Knowledge of Nutrition. (Macmillan.) OSBORNE-The Vegetable Proteins. (Longmans.) PLIMMER-Vitamines and the Choice of Food. (Longmans.) SHERMAN-The Chemistry of Food and Nutrition. (Macmillan.) SHERMAN-Food Products. (Macmillan.) REFERENCE BOOKS SHERMAN AND SMITH-Vitamines. (Chemical Catalog.) SNYDER-Dairy Chemistry. (Macmillan.) THURsTON-Pharmaceutical and Food Analysis. (Van Nostrand.) VULTE AND VANDERBILT-Food Industries. (Chemical Publishing.) Physical Chemistry in Relation to Organic Chemistry BANCROFT--Applied Colloid Chemistry. (McGraw-Hill.) CLARK-Determination of Hydrogen Ions. (Williams & Wilkins.) CLAYTON-Theory of Emulsions and Emulsifications. (Blakiston.) FALK-Chemical Reactions, Their Theory and Mechanism. (Van Nostrand.) FINDLAY-Physical Chemistry and Its Applications in Medical and Bio- logical Sciences. (Longmans.) HATSCHEK-Introduction to Chemistry and Physics of Colloids. (Blakiston.) LEWIs--Valence and the Structure of Atoms and Molecules. (Chemical Catalog.) LOEB-Proteins and the Theory of Colloidal Behavior. (McGraw-Hill.) PAULI-Physical Chemistry in the Science of Medicine. (Wiley.) OsTWALD-Handbook of Colloid Chemistry. (Blakiston.) OSTWALD-Introduction to Theoretical and Applied Colloid Chemistry. (Wiley.) ROBERTSON-The Physical Chemistry of the Proteins. (Longmans.) SMILEs-Relation between Chemical Constitution and Some Physical Prop- erties. (Longmans.) TAYLOR-Chemistry of Colloids. (Longmans.) VAN'T HoFF-Chemistry in Space. (Oxford.) WATSON-Color in Relation to Chemical Constitution. (Longmans.) ZsIGMONDY-Chemistry of Colloids. (Wiley.) Dyestuffs BARNETT--Coal Tar Dyes and Intermediates. (Van Nostrand.) BEACALL, etc.-Dyestuffs and Coal Tar Products. (Appleton.) CAIN-Manufacture of Dyes. (Macmillan.) CAIN-Manufacture of Intermediate Products for Dyes. (Macmillan.) CAIN AND THORPE-Synthetic Dyestuffs and the Intermediate Products for Dyes. (Griffin, London.) DRAPER-Chemistry and Physics of Dyeing. (Blakiston.) FAY-Coal Tar Dyes. (Van Nostrand.) FORT AND LLOYD-The Chemistry of Dyestuffs, a Manual for Students of Chemistry and Dyeing. (Cambridge University Press.) GEORGEVICS AND GRANDMOUGIN-Textbook of Dye Chemistry. (Van Nos- trand.) GREEN-Systematic Survey of the Organic Coloring Matters. (Macmillan.) GREEN-Analysis of Dyestuffs and Their Identification in Dyed and Colored Materials, Lake Pigments, Foodstuffs, etc. (Griffin, London.) 370 REFERENCE BOOKS HEWITT-Synthetic Coloring Matters: Dyestuffs Derived from Pyridine, Quinoline, Acridine and Xanthene. (Longmans.) KNECHT AND FOTHERGILL-Principles and Practice of Textile Printing. (Lip- pincott.) LUCKIESH-Color and Its Application. (Van Nostrand.) MULLIKEN-Method for the Identification of Commercial Dyestuffs. (Wiley.) LOEWENTHAL-Manual of Dyeing. (Lippincott.) PERKIN AND EVEREST-Natural Organic Coloring Matters. (Longmans.) RAMSEY AND WESTON-Artificial Dyestuffs. (Routledge, London.) SHREVE-Dyes Classified by Intermediates. (Chemical Catalog.) ScHuLTz-Farbstoff-Tabellen. (Weidmannsche Buchhandlung, Berlin.) THORPE AND INGOLD-Synthetic Coloring Matters, Vat Colors. (Longmans.) WAHL-Manufacture of Organic Dyestuffs. (Bell, London.) WATSON-Color in Relation to Chemical Constitution. (Longmans.) WHITTAKER-Dyeing with Coal Tar Dyestuffs. (Van Nostrand.) WOOD-The Chemistry of Dyeing. (Van Nostrand.) History of Chemistry ARMITAGE-History of Chemistry. (Longmans.) BRowN-History of Chemistry. (Blakiston.) HAMOR-Chemistry (Vol. IV, Science-History of the Universe). (Current Literature Pub. Co., New York.) HILDITCH-History of Modern Chemistry. (Van Nostrand.) LADENBURG-History and Development of Chemistry Since Lavoisier. (Van Nostrand.) LowRY-Historical Introduction to Chemistry. (Macmillan.) MEYER-History of Chemistry. (Macmillan.) MOORE-History of Chemistry. (McGraw-Hill.) SMITH-Chemistry in America. (Appleton.) THORPE-Essays in Historical Chemistry. (Macmillan.) THORPE-History of Chemistry. (Putnam.) VENABLE-HistOry of Chemistry. (Heath.) Biographical Chemical Society Memorial Lectures. (Gurney & Jackson, London.) FISCHER-Aus Meinen Leben. (Springer, Berlin.) HARROW-Eminent Chemists of Our Time. (Van Nostrand.) HOESCH-Emil Fischer. (Verlag Chemie, Berlin.) MEYER-Victor Meyer. (Akademische Verlagsgesellschaft, Leipzig.) ROBERTS-Famous Chemists. (Macmillan.) TILDEN-Famous Chemists. (Dutton.) VALLERY-RADOT--The Life of Pasteur. (Doubleday.) 371 REFERENCE BOOKS General Reference Books for Organic Chemistry BEILSTEIN-Organische Chemie. (Springer, Berlin.) OLSEN-Chemical Annual. (Van Nostrand.) RICHTER-Lexikon der Kohlenstoffverbindungen. (Voss, Hamburg.) SCUDDER-The Electrical Conductivity and Ionization Constants of Organic Compounds. (Van Nostrand.) SEIDELL-Solubilities of Inorganic and Organic Substances. (Van Nostrand.) STELZNER-Literatur Register der Organischen Chemie. (Vieweg, Braun- schweig.) WINTHER-Zusammenstellung der Patente auf dem Gebiete der Organischen Chemie. (Topelmann, Gieszen.) Popular Books ANON.-A Wonder Book of Rubber. (Goodriqh Rubber Co.) AULD-Gas and Flame. (Doran.) BULL-Chemistry of Today. (Lippincott.) CALDWELL AND SLOSSON-Science Remaking the World. (Doubleday.) COCHRANE-Modern Industrial Progress. (Lippincott.) CREssY-Discoveries and Inventions of the Twentieth Century. (Dutton.) DUNcAN-Chemistry of Commerce. (Harpers.) DUNCAN-Some Chemical Problems of Today. (Harpers.) DUsHMAN-Chemistry and Civilization. (Badger.) FINDLAY-Chemistry in the Service of Man. (Longmans.) FINDLAY-The Treasures of Coal Tar. (Van Nostrand.) FULLER-The Story of Drugs. (Century.) GEER-Reign of Rubber. (Century.) HARROW-Contemporary Science. (Boni & Liveright.) HENDRICK-Everyman's Chemistry. (Harpers.) LAssAR-CHN-Chemistry in Daily Life. (Lippincott.) LowY-Coal Products Chart. (Van Nostrand.) MARTIN-Modern Chemistry and Its Wonders. (Van Nostrand.) MARTIN-Story of a Piece of Coal. (Appleton.) MILLs-Within the Atom. (Van Nostrand.) MooRE--Origin and Nature of Life. (Holt.) PHILIP-Romance of Modern Chemistry. (Lippincott.) RUSSELL-A. B. C. of the Atoms. (Dutton.) SADTLER-Chemistry of Familiar Things. (Lippincott.) Science Service News. (Washington, D. C.) SLossoN-Chats on Science. (Century.) SLossoN-Creative Chemistry. (Century.) SODDY-Science and Life. (Dutton.) STARLING-Feeding of Nations. (Longmans.) SURFACE-Story of Sugar. (Appleton.) 372 MISCELLANEOUS TALBOT--The Oil Conquest of the World. (Lippincott.) TILDEN-Chemical Inventions and Discoveries of the Twentieth Century. (Dutton.) TILDEN-Progress of Scientific Chemistry in Our Own Times. (Van Nos- trand.) TowER--Story of Oil. (Van Nostrand.) YERKES-The New World of Science. (Century.) Miscellaneous ABRAHAM-Asphalts and Allied Substances. (Van Nostrand.) ALEXANDER-Glue and Gelatine. (Chemical Catalog.) ANoN.-New and Non-official Remedies. (Amer. Med. Ass.) ARMSTRONG-The Simple Carbohydrates and Glucosides. (Longmans.) BACON AND HAMOR-American Fuels. (McGraw-Hill.) BACON AND HAMOR-The American Petroleum Industry. (McGraw-Hill.) BARGER-Simpler Natural Bases. (Longmans.) BARNETT-Anthracene and Anthraquinone. (Van Nostrand.) BARROWCLIFF AND CARR-Organic Medicinal Chemicals. (Van Nostrand.) BASKERVILLE-Municipal Chemistry. (McGraw-Hill.) BELL-American Petroleum Refining. (Van Nostrand.) BoGUE-Gelatine and Glue. (McGraw-Hill.) BONE-Coal and Its Scientific Uses. (Longmans.) BROOKs-Chemistry of the Non-benzenoid Hydrocarbons and Their Simple Derivatives. (Chemical Catalog.) CAIN-The Chemistry of Diazo Compounds. (Arnold, London,) Chemical Engineering Catalog. (Chemical Catalog.) CHRISTIAN-Disinfection and Disinfectants. (Scott, Greenwood, London.) CLAISEN-Beet Sugar Manufacture. (Wiley.) CLAYTON-Margarine. (Longmans.) COHN-Indicators and Test Papers. (Wiley.) Condensed Chemical Dictionary. (Chemical Catalog.) COOPER-Textile Chemistry. (Dutton.) CROSS AND BEvAN-Cellulose. (Longmans.) DAKIN AND HUNHARNE-Handbook of Antiseptics. (Macmillan.) DORLAND-American Illustrated Medical Dictionary. (Saunders.) DUBOSC AND LUTTRINGER-Rubber-Its Production, Chemistry and Synthesis. (Griffin, London.) ELLIs-Synthetic Resins. (Chemical Catalog.) ELLIs-Hydrogenation of Oils. (Van Nostrand.) FALK-The Chemistry of Enzyme Actions. (Chemical Catalog). FRIES AND WEsT--Chemical Warfare. (McGraw-Hill.) FRY-Electronic Conception of Valence and the Constitution of Benzene. (Longmans.) GIBsoN-Chemistry of Dental Materials. (Benn Bros., London.) GILDMEISTER AND HOFFMAN-The Volatile Oils. (Wiley.) GRocGGINs-Aniline and its Derivatives. (Van Nostrand.) 373 REFERENCE BOOKS HALE-Synthetic Use of Metals in Organic Chemistry. (Churchill, London.) HAMOR AND PADGETr-The Technical Examination of Crude Petroleum, Petroleum Products and Natural Gas. (McGraw-Hill.) HANTZSCH-The Elements of Stereochemistry. (Chemical Publishing.) HARDEN-Alcoholic Fermentation. (Longmans.) HOWLEY-Wood Distillation. (Chemical Catalog.) KoPPE-Glycerine. (Van Nostrand.) KOPPERS CoMPANY-By-product Coke and Gas Oven Plants: Benzol Recov- ery Plants, Tar Distilling Plants: Ammonia Recovery Apparatus. (Kop- pers Co., Pittsburgh.) JONEs-Nucleic Acids. (Longmans.) LACHMAN-The Spirit of Organic Chemistry. (Macmillan.) LANDOLT-The Optical Rotating Power of Organic Substances and Its Prac- tical Applications. (Chemical Publishing.) LEATHES-The Fats. (Longmans.) LESLIE-Motor Fuels. (Chemical Catalog.) LEwKOWITSCH-Chemical Technology and Analysis of Oils, Fats and Waxes. (Macmillan.) LOB AND LORENz-Electrochemistry of Organic Compounds. (Wiley.) LUFF-The Chemistry of Rubber. (Van Nostrand.) MAcKENZIE--Sugars and Their Simple Derivatives. (Lippincott.) MARSHALL-Explosives. (Blakiston.) MARTIN-The Modern Soaps and Detergent Industry. (Van Nostrand.) MAssELoN-Celluloid. (Lippincott.) MATTHEWS-The Textile Fibers. (Wiley.) MERcK-Chemical Reagents. (Van Nostrand.) MORGAN-Organic Compounds of Arsenic and Antimony. (Longmans.) MYDDLETON AND BARNY-Fats: Natural and Synthetic. (Van Nostrand.) McINTOsH-Industrial Alcohol. (Van Nostrand.) McKEE-Shale Oil. NATIONAL FORMULARY-Amer. Pharmaceutical Assoc. (Lippincott.) OPPENHEIMER-Ferments and Their Actions. (Lippincott.) PALMER-Carotinoids and Related Pigments. (Chemical Catalog.) PARRY-Chemistry of Essential Oils and Artificial Perfumes. (Scott, Green- wood, London.) PARRY-Gums and Resins. (Scott, Greenwood, London.) PARRY-Perfumery. (Scott, Greenwood, London.) PATTERSON-French-English Dictionary for Chemists. (Wiley.) PATTERSON-German-English Dictionary for Chemists. (Wiley.) PoucHER-Perfumes and Cosmetics. (Van Nostrand.) The Pharmacopoeia of the United States of America. (Blakiston.) PICTET-The Vegetable Alkaloids. (Wiley.) PILCHER, BUTLER AND JoNEs-What Industry Owes Technical Science. (Con- stable, London.) PLIMMER-Chemical Constitution of the Proteins. (Longmans.) PoRRrr--The Chemistry of Rubber. (Van Nostrand.) PRIcE-Atomic Form. (Longroans.) PRINz-Dental Formulary. (Kempton, London.) 374 PERIODICALS RAIZISS AND GAVRON-Organic Arsenic Compounds. (Chemical Catalog.) REDWOOD-Petroleum. (Lippincott.) REMINGTON, ETc.-Dispensatory of the U. S.'of America. (Lippincott.) ROLFE-The Polariscope. (Macmillan.) SINDALL-Paper Technology. (Lippincott.) SMITH-T.N.T. and Other Nitrotoluenes. (Van Nostrand.) SPARKs-Chemical Literature, and Its Use. (University of Illinois.) SPIELMAN-The Genesis of Petroleum. (Van Nostrand.) STEWART-Stereo-Chemistry. (Longmans.) TRESSLER-Marine Products. (Chemical Catalog.) TRIMBLE-Tannins. (Lippincott.) WALTER-Manual for Essence Industry. (Wiley.) WATTrs-Dictionary of Chemistry. (Longmans.) WERNER-Chemistry of Urea. (Longmans.) WEST AND GILMAN-Organomagnesium Compounds in Synthetic Chemistry. (National Research Council.) WHITMORE-Organic Compounds of Mercury. (Chemical Catalog.) WILsoN-Chemistry of Leather Manufacture. (Chemical Catalog.) WOOLMAN AND McGowAN-Textiles. (Macmillan.) WORDEN-Technology of Cellulose Esters. (Van Nostrand.) WREN-The Organo-Metallic Compounds of Zinc and Magnesium. (Van Nostrand.) Periodicals Annales de Chimie et de Physique. Berichte der Deutschen Chemischen Gesellschaft. Chemical Abstracts. Chemical and Metallurgical Engineering. Chemisches Zentralblatt. Comptes R ~r dus. Helveti=-. Ch.mica Acta. Journ.i ot Industrial and Engineering Chemistry. Journal of the American Chemical Society. Journal of the Chemical Industry. Journal of the Chemical Society of London. Liebig's Annalen der Chemie. Monatshefte fir Chemie. 375 INDEX A Accelerator, 226 Acenaphthene, 287 Acetaldehyde, 70, 75 properties, 71, 72, 73 Acetamide, 108, 112 Acetanilide, 225 Acetic acid, chart, facing p. 85 Acetic acid, 84 glacial, 84 Acetic anhydride, 107, 108 preparation, 108 Acetoacetic acid, 127 Acetoacetic ester, 127 uses, 127 Acetone, chart, facing p. 78 Acetone, 70, 78 properties, 71, 72, 73 Acetonitrile, 155 Acetophenone, 248 Acetyl acetic acid, 127 Acetyl chloride, 109 preparation, 109 properties, 109 Acetylene, 35 preparation, 35 properties, 36 series, 34 Acetylides, 36 Acetyl salicylic acid, 272 Acids, table, 83 Acid amides, 111 identification, 331 preparation, 112 properties, 112 Acid anhydrides, 107 identification, 331 preparation, 108 Acid hydrolysis, 130 Acid imides, identification, 331 Acids, 79 identification, 330 nomenclature, 79 preparation, 81 properties, 82 substituted, 80 type of, 80 Acids, aromatic, 263 Acids, dibasic, unsaturated, 88 Acids, halogen substituted, 117 preparation, 117 properties, 118 Acids, monobasic, 81, 86 Acids, unsaturated, monobasic, 85 Acridine, 318 Acriflavine, 318 Acrolein, 61, 77 Acrylaldehyde, 77, 103 Acrylic acid, 85 Acyl halides, 109 identification, 331 Addition, 210 Adenine, 150 Adrenaline, 342 Alanine, 141, 146 Albolene, 29 Albumins, 143 Albuminoids, 144 Alcohol, denatured, 59 Alcohol, ethyl, 58 preparation, 58 Alcohols, 48 absolute, 58 aromatic, 235 identification, 328 nomenclature, 48 377 BUTANES (Why may propane be called ethyl methane, or dimethyl methane, or methyl ethane, or methyl ethyl?) (If C3Hs is propane, what would its radical, C3H7, be called?) We pointed out that in ethane we have but one mono-sub- stitution product and two di-substitution products, and we saw how the graphic formulas helped to explain these facts. When we come to propane, we find that two mono-substitution products are possible, one differing from the other in physical and chemical properties. Here again the graphic formulas are helpful in ex- plaining experimental facts: H.H H H H H I I I H-C-C-C-H H-C-C-C-H H HI HI H (1) (2) for it will be seen that in (1) the iodine atom is attached to a carbon atom, which in turn is attached to two hydrogen and one carbon atoms, whereas in (2) the iodine atom is attached to a carbon atom which in turn is attached to two carbon and one hydrogen atoms. Butanes, C4H10o.-Two butanes with this formula are known. In the preceding paragraph we pointed out that there are two isomeric propyl iodides which, for convenience, we shall now write according to the " structural " or " constitutional " for- mulas. CH3 CH2 CH2I and CH3 CHI- CH31 (1) (2) Now, it may be asked, what will happen if first (1) and then (2) are treated with methyl iodide in the presence of sodium? Are 1 Periods are often used in place of bonds when writing structural or constitutional formulas, so that CH3,CH2-CH2I really means CH3--CH2-CH2,I, which in turn indicates HHH I I I H----C-C--I HHH As the student proceeds with his studies in organic chemistry, he will find it unnecessary to indicate either dots or dashes for at least some of the simpler types of compounds. 378 Alcohols, polyatomic, 62 preparation, 53 primary, 50 properties, 56 secondary, 51 table, 57 tertiary, 51 Aldehyde resin, 76 Aldehydes, aromatic, 245 properties, 246 Aldehydes, 67 identification, 329 nomenclature, 67 preparation, 69 properties, 69 test for, 76 Aldol, 76 Aliphatic compounds, 16 Alizarin, 300 Alkaloids, 319 identification, 334 Alkyl cyanides, 155 preparation, 155, 156 properties, 156 Alkyl halide, 40 preparation, 41 properties, 42 table, 41 Alkyl isocyanides, 156 preparation, 156 properties, 156 Allantoin, 152 Alloxan, 152 Allyl alcohol, 63 Allyl ether, 66 Allyl isothiocyanate, 15 Aluminium carbide, 18 Amidol, 268 Amines, aliphatic, 132 identification, 332 preparation, 134 primary, 132, 133 properties, 134 secondary, 134 tertiary, 134 types, 132 Amines, aromatic, 222 preparation, 223 INDEX Amiues, reactions, 224 Amino acid, table, 146 Amino acids, 141 nomenclature, 137 preparation, 137 properties, 138 Aminophenol, 267 Ammonium carbamate, 179 Ammonium carbonate, 179 Amygdalin, 167 Amyl butyrate, 96 Analysis, elementary, 10 proximate, 10 ultimate, 10 Anesthesine, 273 Anethole, 267 Anhydrides, inner, 119 Aniline, 224 Aniline hydrochloride, 225 Anisaldehyde, 270 Anisole, 238, 243 Anthocyanins, 336 Anthracene, 285 Anthranilic acid, 274 Anthraquinone, 286 Antifebrin, 225 Antipyrine, 311 Applications of organic chemistry, 4 Arabinose, 161 Arabitol, 62 Arbutin, 167 Arginine, 143, 146 Argyrol, 147 Aromatic compounds, 16 Arsanilic acid, 322 Arsenic compounds, 186, 322 Arsenophenylglycine, 322 Artificial silk, 172' Aseptol, 266 Aspartic acid, 142, 146 Aspirin, 272 Asymmetric carbon atom, 122 Atoxyl, 322 Atropine, 320 Auxochrome, 291 Azobenzene, 220, 234 Azo compounds, 222, 229 identification, 333 INDEX Azo compounds, reactions, 229 Azoxybenzene, 220 B Baekeland, portrait, 240 Baeyer, portrait, 315 Bakelite, 74, 238 Barbital, 115 Bases, organic, 132 Bayer, "205," 301 Beeswax, 103 Benedicts' reagent, 165 qualitative, 165 quantitative, 165 Benzal chloride, 215 Benzaldehyde, 245 Benzaldoxime, 247 Benzamide, 255 Benzene, 191, 199, 201 constitution, 191 preparation, 202 structure, 194, 197 Benzenediazonium chloride, 230 Benzenedisulfonic acid, 216 Benzencsulfonic acid, 216 Benzenesulfonyl chloride, 217 Benzidine, 234 Benzine, 199 Benzohydrol, 236 Benzoic acid, 253 Benzoic anhydride, 255 Benzoin, 249 Benzol, 199 Benzonitrile, 255 Benzophenone, 236, 248 Benzoquinone, 250 Benzotrichloride, 215 Benzoyl chloride, 247 Benzyl alcohol, 235 Benzylamine, 222 Benzyl chloride, 210 Benzylidene chloride, 215 Benzyl cyanide, 256 Betaine, 105 Bile pigments, 338 Biuret, 114 reaction, 114, 146 Boiling points, 362-363 Borneol, 306 Bromal, 76 Bromoaniline, 225 Bromoform, 46 Brucine, 320 Butane, n-, 24 Butanes, 23 Butanone, 68 Butylenes, 34 Butyn, 274 Butyraldehyde, 68 Butyric acid, 85, 98, 177 Butyrolactam, 141 Butyrolactone, 121 C Cacodyl, 186 Cacodyl oxide, 186 Cadaverine, 136 Caffeine, 153 Calcium carbide, 37 Calcium cyanamide, 155 Calcium formate, 70 Camphor, 305 artificial, 303, 305 natural, 305 Candle, 85 Cane sugar, 169 Caproic acid, 177 Carbazole, 285, 318 Carbinol, 49, 57 Carbocyclic compounds, 188, 309 Carbohydrates, 160, 174 identification, 332 Carbou monoxide, 84, 87 Carbonyl group, 67 Carbon tetrachloride, 46 preparation, 46 uses, 46 Carboxyl group, 79 Carbylamine, 156 reaction, 134 Carnauba wax, 103 Carotin, 336 Carvone, 305 Catalase, 340 Celluloid, 172, 305 Cellulose, 171 379 INDEX Cellulose nitrate, 172 Cellulose xanthate, 185 Cephalin, 105 Cerasin, 105 Cetyl alcohol, 103 Chinese wax, 103 Chitin, 171 Chloral, 76 Chloral alcoholate, 76 Chloral hydrate, 76 Chloramine-T, 266 Chloretone, 45 Chloroacetic acid, 119 Chloroanilines, 262 Chlorobenzene, 214 Chloroform, 44 preparation, 44 properties, 45 uses, 45 Chlorophyll, 335 Chloropicrin, 45 Chlorotoluenes, 211, 215, 262 Cholesterol, 105 Choline, 104 Chondroitin, 171 Chromophore, 291 Chromotropic acid, 283 Chrysene, 287 Cinchonine, 320 Cinnamaldehyde, 247 Cinnamic acid, 257 Cis-form, 89 Citral, 78 Citrene, 306 Citric acid, 127 Citronellal, 306 Closed chain compounds, 188 Coal, destructive distillation, 6, 199 Coal gas, 18 Cocaine, 320 Codeine, 321 Collodion, 172 Cologne spirit, 58 Colophony, 303 Congo red, 299 Coniine, 320 Cordite, 172 Coumarin, 313 Cream of tartar, 127 Creatinine, 115 Creatine, 114 Cresols, 230 Cresylic acid, 239 Crisco, 101 Crotonic acid, 85, 119 Crude oil, 27 Cyanamide, 155 Cyanides, 154 identification, 333 Cyanogen, 154 Cyanogen chloride, 155 Cyanuric acid, 157 Cyclic compounds, 188 Cyclobutane, 189 Cyclohexane, 189 Cycloparaffins, 190 Cyclopentane, 189 Cymene, 205, 302 Cystine, 142, 146 Cytosine, 150 D De-amination, 178 Decalin, 283 Denatured alcohol, 59 Dextrins, 171 Diacetic acid, 128, 178 Diamines, 135, 228 Diaminobenzene, 228 Diastase, 58 Diazoaminobenzene, 233 Diazobenzene chloride, 230 Diazo compounds, 222, 229 Diazo reactions, 229 Diazotization, 230 Dichloroacetic acid, 117 Dichloramine-T, 266 Dichlorobenzene, p-, 214 Dichloroethyl sulfide, 184 Diethyl nitrosoamine, 135 Diethyl phthalate, 258 Diethyl sulfate, 95, 243 Dihydrobenzene, 206 Dimethylaniline, 222 Dimethylamine, 134, 228 380 INDEX Dimethylammonium iodide, 134 Dimethyl glyoxal, 76 Dimethyl glyoxime, 77 Dimethyl sulfate, 95 Dionine, 321 Dipeptide, 145 Diphenylacetylene, 205 Diphenylamine, 222, 228 Diphenylethylene, symmetrical, 205 Diphenylguanidine, 226 Diphenylmethane, 205 Dippel's oil, 310, 312 Disaccharides, 161 Distillation, destructive, 7 Distillation, fractional, 7 Dulcin, 269 Dyes, 288 acid, 290 adjective, 288 artificial, 288 basic, 290 direct cotton, 290 ingrain, 291 mordant, 291 natural, 288 substantive, 288 sulfur, 291 theory, 290 uses, 288 vat, 291 Dyes, acridine, 296 anth-aquinone, 297 azine, 297 azo, 293 diphenylmethane, 294 indigo, 298 indophenol, 296 nitro, 292 nitroso, 292 oxazine, 296 pyrazolone, 293 quinoline, 296 stilbene, 293 sulfur, 297 thiazine, 297 triphenylmethane, 294 xanthone, 295 Dynamite, 62 Ehrlich, 323 Elements in organic compounds, 5 Emetine, 321 Enzymes, 339 table, 340 Erepsin, 340 Erythritol, 62 Esterification, 96 Esters, 90, 93 identification, 331 preparations, 92 properties, 92 Ethane, 20 Ethanol, 58 Ethenol, 63 Ethereal salts, 94 Ethers, 64, 65 aromatic, 243 identifications, 329 mixed, 64 preparation, 64, 65 properties, 65, 66 uses, 66 Ethyl acetate, 96, 110 Ethyl alcohol, 58 chart, facing p. 59 percentages in beverages, 59 properties, 59 uses, 59 Ethylamine, 156 Ethylbenzene, 204 Ethyl benzoate, 254 Ethyl bromide, 43 Ethyl carbonate, 111 Ethyl chloride, 43 Ethyl dichloroarsine, 186 Ethyl ether, 64 Ethyl formate, 96 Ethyl gas, 187 Ethyl hydrogen sulfate, 95 Ethyl malonate, 97 Ethyl methyl carbinol, 54 Ethyl nitrate, 95 Ethyl nitrite, 94, 158 Ethyl nonyl ketone, 69 Ethyl oxalate, 97 Ethyl oxide, 65 381 INDEX Ethyl propyl ether, 64 Ethyl sulfide, 182 Ethyl sulfuric acid, 95 Ethylene, 31 preparation, 31, 32 properties, 32, 33 Ethylene bromide, 43 Ethylene chlorohydrin, 60 Ethylene cyanide, 88 Ethylenediamine, 135 Eugenol, 267 F Fats, 99, 176 table, 100, 102 Fehling test, 76, 165 Fermentation, 7, 58 Ferric ammonium citrate, 127 Fire damp, 19 Fischer, portrait, 139 Fittig, synthesis, 199 Flavones, 336 Formaldehyde, 74 chart, facing p. 74 Formalin, 74 Formic acid, 83 Formula, empirical, 11 molecular, 11 structural, 23 Friedel-Craft, reaction, 200, 248, 254 Fructose, 168 Fulminic acid, 158 Fumaric acid, 88 Furan, 309 Furfural, 310 Fusel oil, 60 G Galactans, 172 Galactose, 168 Gallic acid, 277 Gasoline, 28 purification, 28 Geranial, 78 Geraniol, 306 Globulins, 143 Glossary, 359-361 Glyoxylic acid, reaction, 147 Glycuronic acid, 166 Glucosamine, 168 Glucosazone, 163 Glucose, 161 properties, 164 proof of structure, 162, 163 Glucosides, 167 identification, 332 Glutamic acid, 142, 146 Glutelins, 144 Glyceraldehyde, 175 Glycerol, 61, 93 properties, 61 uses, 61 Glyceryl margarate, 101 Glyceryl phosphate, 95 Glyceryl trinitrate, 61, 95 Glycine, 138, 145 Glycine anhydride, 141 Glycocoll, 141, 146 Glycogen, 171 Glycol, 60 Glycol ether, 66 Glycolic acid, 121 Glycolide, 121 Glycoproteins, 144 Glycuronic acid, 166 Glycylglycine, 145 Glyoxal, 76 Gomberg, 206 portrait, 207 Griess', diazo reaction, 229 Grignard's, reagent, 43 portrait, 55 reaction, 54 Guaiacol, 266 Guanidine, 114 Guanine, 151 Gums, 172 Gum arabic, 172 Gum tragacanth, 172 H H acid, 283 Halogen compounds, 210 identification, 328 382 Halogen compounds, preparation, 211 properties, 212 Halogen substituted acids, 117 preparations, 117 properties, 118 Hemicellulose, 172 Hemoglobin, 144, 337 Heroine, 321 Heterocyclic compounds, 188, 309 Hexahydrobenzene, 206 Hexamethylene, 207 Hexamethylenetetramine, 74 Hexaphenylethane, 206 Hippuric acid, 256 Homatropine, 320 Hormones, 342 Histidine, 143, 146 Histones, 144 Hofmann reaction, 112, 133, 274, 316 Homologous series, 25 Hopkins-Cole reaction, 147 Hydrazobenzene, 220 Hydrobenzamide, 246 Hydrocarbons, 30 acetylenes, 30 aromatic, 199, 201-206 hydroaromatic, 206 identification, 327 nitration, 201 olefins, 30 oxidation, 201 preparation, 199 properties, 201 reactions, 201 sources, 199 sulfonation, 201 unsaturated, 30 Hydrocarbons saturated preparation, 27 properties, 27 Hydrocinnamic acid, 257 Hydrocyanic acid, 154 Hydrogen cyanide, 154 Hydroxy acids, 120 preparations, 120 properties, 121 Hydroxyazobenzene, p-, 234 Hypnone, 248 Hypoxanthine, 150 I Identification of compounds, 327-334 Indican, 314 Indigo, 314 Indigo carmine, 317 Indole, 314 Indoxyl, 314 Inner anhydrides, 119 Inner salts, 140 Inositol, 208 Insulin, 343 Intarvin, 1, 101 Intermediates, dyes, 214 Inulin, 171. Invertase, 340 Iodal, 76 Iodine number, 102 Iodoform, 46 Iodol, 311 Isoamyl acetate, 96 Isoamyl alcohol, 60 Isoamyl isovalerate, 96 Isoamyl nitrite, 94 Isobutane, 24 Isocyanic acid, 157 Isocyanides, identification, 333 Isoelectric point, 138 Isoeugenol, 267 Isomerism, 21 anti-type, 247 cis-type, 89 optical, 122 stereo, 122 syn-type, 247 trans-type, 89 Isopentane, 24 Isophthalic acid, 357 Isoprene, 37, 306 Isopropyl alcohol, 60 Isoquinoline, 313 Isovaleric acid, 85 Kahn, 101 Kekul6, portrait, 192 INDEX 383 INDEX Ketones, 67 aromatic, 248 identification, 329 mixed, 69 nomenclature, 68 preparation, 69 simple, 69 Knoop's --oxidation theory, 177 Ketonic hydrolysis, 130 Kolbe-Schmitt, reaction, 271 L Lactase, 340 Lactic acid, 175 Lactones, 119 Lactose, 170 Lake, 290 Lanolin, 103 Lead tetraethyl, 6, 187 Le Bel, 122 Lecithin, 104 Leucine, 141, 146 Levulose, 168 Lewisite, 186 Limonene, 303 Linoleic, acid, 86 Lipase, 340 Lipoids, 104 Luminal, 115 Lysine, 136, 142, 146 M Magnesium citrate, 127 Magnesium ethyl iodide, 187 Malachite green, 299 Maleic acid, 88, 125 Maleic anhydride, 109 Malonamide, 115 Malonic acid, 87 Malonic ester, 97 uses, 97 Maltase, 170, 340 Maltose, 170 Manna, 63 Mannans, 172 Mannitol, 62 Marsh gas, 18 Medicated alcohol, 59 Melanins, 338 Mellitic acid, 260 Melting points, 362, 363 Menthane, 304 Menthol, 304 Menthone, 304 Mercaptans, 182, 183 preparation, 183 Mercaptides, 183 Mercaptol, 184 Mercerized cotton, 172 Mercuric benzoate, 326 Mercuric fulminate, 158 Mercuric salicylate, 326 Mercurochrome-220, 326 Mercury compounds, 326 Mesitylene, 204 Metaldehyde, 75 Metanilic acid, 265 Metaproteins, 145 Methane, 18 occurrence, 18 preparation, 18 properties, 19 Methanol, 57 chart, facing p. 57 properties, 57 preparation, 57 uses, 57 Methyl alcohol, 57 Methylaniline, 227 Methyl anthranilate, 274 Methylbenzene, 202 Methyl chloride, 43 Methyl cyanide, 155 Methyl glucoside, 167 Methylene iodide, 44 Methyl isocyanide, 134, 156 Methyl isonitrile, 156 Methyl orange, 298 Methyl salicylate, 272 Metol, 268 Michler's ketone, 249 Millon's reaction, 147 Molisch, reaction, 147 reagent, 164 Monosaccharides, 160 Mordant, 290 384 INDEX Morphine, 321 Mucilages, 172 Muscarine, 104 Mustard gas, 184 Myricyl alcohol, 103 Myricyl palmitate, 97 Myronic acid, 167 N Naphthalene, 278 Naphthalene substituents, table, 284 Naphthalene sulfonic acid, 281 Naphthalic acid, 282 Naphthionic acid, 283 Naphthoic acid, 282 Naphthol, P-, 281 Naphthol, a-, 281 Naphthoquinones, 283 Naphthylamine, fl-, 282 Naphthylamine, a-, 282 Narcotine, 321 Neosalvarsan, 325 Nerolin, 281 Niootine, 320 Nitration, 201 Nitrile, 155 Nitroanilines, 262 Nitrobenzene, 220 Nitrobenzoic acid, 272 Nitro compounds, 218 identification, 333 preparation, 219 properties, 220 reduction, 220 reduction products, 220 Nitroethane, 43 Nitroglycerine, 61 Nitrolime, 155 Nitronaphthalene, 281 Nitrophenols, 263 Nitrosobenzene, 220 Nitroso compounds, 135 Nitrosodimethylamine, 159 Nitrosodimethylaniline, 224, 227 Nitrosomethylaniline, 224 Nitroso- f- Naphthol, 282 Nobel, 62 Nomenclature, 344-358 Novocaine, 273 Nucleic acid, 149 Nuclein, 149 Nucleoproteins, 144, 149 Nucleoside, 149 Nujol, 29 O Octyl acetate, 96 Oil of anise, 267 Oil of bitter almonds, 245 Oil of caraway, 305 Oil of cinnamon, 247 Oil of cloves, 267 Oil of garlic, 184 Oil of lemon, 303 Oil of lime, 303 Oil of mirbane, 220 Oil of peppermint, 304 Oil of sassafras, 267 Oil of thyme, 241 Oil of turpentine, 203 Oil of wintergreen, 272 Oils, 99 properties, 102 table, 100 Oils, essential, 307 Oils, hydrogenation, 101 Olefin series, 31 Oleic acid, 85 Olein, 99 Oleomargarine, 101 Optical activity, 122 Organic compounds, 2 analysis, 9 purification, 8 Organic type formulas, facing p. 16 Organo-metallic compounds, 187 Oxalic acid, 86 preparation, 86 Oxalyl chloride, 111 Oxamide, 115 Oxidation, 201 P Palmitic acid, 85 Palmitin, 99 Paraffins, 18 385 INDEX Paraffin series, table, 26 Paraform, 75 Paraformaldehyde, 75 Paraldehyde, 75 Parchment paper, 172 Paris green, 92 Pasteur, portrait, 124 Pectins, 172 Pentane, 24 Pento es, 161 Pepsin, 178, 340 Peptones, 145 Perkin, portrait, 289 reaction, 257 Peroxidase, 340 Petrolatum, 29 Petroleum, 13, 19, 27, 28 cracking, 29 distillation, 28 distillation chart, facing p. 29 occurrence, 28 products derived, 28 Phenacetin, 269 Phenanthrene, 285, 287 Phenetidine, 269 Phenetole, 243 Phenol, 237 properties, 237 Phenols, identification, 329 Phenolphthalein, 258 Phenolsulfonephthalein, 259 Phenolsulfonic acid, 238, 265 Phenoltetrachlorophthalein, 259 Phenylacetaldehyde, 247 Phenylacetic acid, 253, 256 Phenylacetylene, 205 Phenyl alanine, 141, 146 Phenylamine, 224 Phenylenediamine, 228 Phenyl ether, 243, 244 Phenylhydrazine, 233 Phenylhydroxylamine, 220 Phenyl salicylate, 272 Phloridzin, 167 Phloroglucinol, 242 Phosgene, 45, 111 Phosphoproteins, 144 Phosphorus compounds, 185 Phrenosin, 105 Phthalic acids, 257 Phthalic anhydride, 258 Phthalimide, 258 Phytosterol, 105 Picramic acid, 264 Picric acid, 263 Pigments, 335 animal, 337 plant, 335 Pilocarpine, 321 Pinene, 303 Pinene hydrochloride, 305 Piperidine, 312 Piperine, 320 Pituitrin, 343 Polypeptide, 145 Polysaecharides, 161 Potassium acid tartrate, 127 Potassium antimonyl tartrate, 127 Procaine, 274 Proflavine, 318 Prolamines, 144 Proline, 146, 310 Propane, 22 Propanone, 68 Propenol, 48 Propine, 37 Propionaldehyde, C8 Propionic acid, 85 Propylene, 34 Protamines, 143 Proteins, 143, 178 composition, 145 constitution, 145 identification, 334 reactions, 146 Proteoses, 145 Prussic acid, 154 Ptyalin, 340 Purine, 150 identification, 334 Putrefaction, 8 Putrescine, 136 Pyrazole, 311 Pyrazolone, 311 Pyrene, 46 Pyridine, 312 386 INDEX Pyrimidine, 150 . Pyrocatechol, 241 Pyrogallol, 242 Pyroligneous acid, 57, 84 Pyromucic acid, 310 Pyroxylin, 172 Pyrrole, 310 Pyrrolidine, 310 Pyruvic aldehyde, 175 Q Quaternary bases, 135 Quinine, 320 Quinol, 242 Quinoline, 312 Quinolinic acid, 313 Quinone, 250 identification, 332 R Racemic acid, 126 Radicals, 340-356 Raffinose, 170 Redmanol, 74 Red oil, 86 Reference Books, 365-375 Reimer-Tiemann, reaction, 270, 271, 313 Remsen, portrait, 276 Rennin, 340 Resorcin, 241 Resorcinol, 241 Rhodinal, 268 Ribose, 161 Rochelle salt, 127 Rosin, 303 Ruberythric acid, 167 Rules, substitution in the benzene ring, 203 S Sabatier and Senderens, reaction, 208 Saccharic acid, 166 Saccharin, 275 Safrole, 267 Salicin, 167 Salicyl alcohol, 269 Salicylaldehyde, 270, 313 Salicylic acid, 271 Saligen'in, 269 Salol, 272 Salts, 90, 92 preparation, 91 properties, 91 Salvarsan, 323, 324 Sandmeyer, reaction, 231 Saponification, 94, 96 Saponification number, 102 Saturated hydrocarbon, 18, 25 nomenclature, 25 properties, 27 Schiff test, 76 Schweitzer's reagent, 171 Secretin, 343 Seidlitz powders, 127 Seliwanoff test, 169 Serine, 146 Silicon tetraethyl, 187 Silk, artificial, 172, 185 Silver fulminate, 158 Skatole, 317 Skraup's reaction, 313 Smokeless powder, 172 Soaps, 92, 93, 102 Sodium benzenesulfonate, 217 Sodium benzoate, 254 Sodium citrate, 127 Sodium ethylate, 56 Sodium ethyl mercaptide, 182 Sodium formate, 83 Sodium phenolate, 217 Sodium salicylate, 272 Sources of organic compounds, 6 Spermaceti, 103 Sphingomyelin, 105 Stains, 300 Starch, 171 Steapsin, 340 Stearic acid, 85 Stearin, 99 Stilbene, 205 Strychnine, 320 Styrene, 205 Substitution, 13, 20 rules, 203 Substrates, 339 Succinamide, 115 387 24 SATURATED HYDROCARBONS OR PARAFFINS we going to get two identical compounds? This is hardly likely, since (1) and (2) are different. In reality, the two compounds obtained are different,-different in properties, but alike in having the same molecular formula, C4H10. CH3- CH2 -CH2 I+2Na+I CH3 -CH CH3 CH2 CH2 CH3 +2NaI (3) CH3 CH I .CH3 - CH3 CH-CH3 + 2NaI + 2Na CH3 + I CH3 (4) (3) and (4) are isomeric, (3) being known as normal (" straight- chain ") or n- butane, and (4) as iso- (" branched-chain ") butane. (Why may normal butane be given any one of the following names: methylpropane, ethylethane, diethyl, propylmethane and symmetrical dimethylethane? Why may isobutane also be called trimethylmethane and unsymmetrical dimethylethane?) (If two of the hydrogens in ethane which are attached to two different carbon atoms are replaced by methyl groups, we get butane or symmetrical dimethylethane: H H CH3 CH3 I I I I H-C-C-H -- H-C-C-H I I I I H H H H If, however, the two hydrogen atoms replaced by two methyl groups are on the same carbon atom, then we get isobutane, or unsymmetrical dimethylethane.) Pentanes, CsH12.-Three pentanes are known: CH3 CH2 CH2 CH2 - CH3 n-pentane CH3-CH-CH2 CH3 isopentane CH3 CH3 CH3-U-C-CH3 tetramethylmethane CH3 INDEX Succinic acid, 87 Succinic anhydride, 88, 109 Succinimide, 115 Sucrase, 340 Sucrol, 269 Sucrose, 169 Sugar, 169 Sugar of lead, 92 Sulfanilic acid, 226, 264 Sulfarsenol, 325 Sulfides, 183 preparation, 183 Sulfoacetic acid, 81 Sulfobenzoic acid, 274 Sulfonal, 184 Sulfonation, 201 Sulfonic acids, 216 identification, 330 preparations, 216 properties, 217 Sulfur compounds, 182 identification, 334 Sulfuric ether, 65 Sweet spirit of nitre, 94 T Tannic acid, 277 Tannin, 277 Tartar emetic, 127 Tartaric acid, 125 Taurine, 185 Tautomerism, 129, 243 Terephthalic acid, 257 Terpenes, 302 identification, 334 Terpineol, 305 Tetrahydrobenzene, 206 Tetralin, 283 Tetramethylammonium 135 Tetramethylmethane, 24 Tetraphenylethylene, 205 Tetryl, 219 Theine, 153 Theobromine, 153 Theophylline, 153 Thioacetic acid, 185 Thioacetone, 182, 185 hydroxide, Thioacids, 183 Thioalcoholate, 182 Thiocarbanilide, 226 Thiophene, 311 Thiophenol, 217 Thiourea, 185 Thrombin, 340 Thymine, 150 Thymol, 241 Thyroxin, 343 Tin diethyl, 187 T. N. A., 219 T. N. T., 219 Tolane, 205 Toluene, 202 Toluenesulfonic acids, 216, 266 Toluic acid, 256 Toluidine, 227 Trans-form, 89 Tribromophenol, 237 Trichloroacetic acid, 117, 119 Tricresol, 239 Trimethylamine, 134 Trimethylarsine, 186 Trimethyl carbinol, 54 Trimethylphosphine, 186 Trinitrotoluene, 219 Triphenylamine, 222 Triphenylguanidine, 226 Triphenylmethane, 205 Triphenylmethyl, 206 Triphenyl phosphate, 238, 305 Trisaccharides, 161 Trithioacetaldehyde, 182, 185 Tryparsamide, 326 Trypsin, 146, 178, 340 Tryptophan, 142, 146, 317 Tyrosine, 142, 146 U Uracil, 150 Urea, 1, 113, 152 determination, 114 preparation, 113 properties, 113 Urease, 340 Uric acid, synthesis, 151 Urotropine, 74 388 INDEX V Valence, electronic conception, 11, 14 Valine, 141, 146 Vanillin, 270 Van Slyke, 140 van't Hoff, 122 Verdigris, 92 Vinegar, 84 Viscose, 172, 185 Vitamins, 340 W Waxes, 103 Williamson, synthesis, 64 W6hler, 1, 113 Wood alcohol, 57 Wurtz, synthesis, 21, 42 X Xanthic acid, 185 Xanthine, 151 Xanthoproteic, reaction, 147 Xanthophyll, 336 Xylene, 204 Xylidine, 227 Xylose, 161 Y Yara-yara, 281 Z Zinc ethyl, 187 Zinc methyl iodide, 187 Zymase, 340 389 LIGHT GASOLINE M OIL AGITATORS LIGHT KEROSENE Y OIL AGITATORS STORAGE FINISHED STORAGE PRESSURE STILLS GAS OIL RESIDUUM RESIDUUM STILLS PRESSURE DISTILLATE GAS OILS FUEL OIL GAS OIL LUBRICATING D LIGHT OIL RERUN AGITATORS STILLS RDPD- .FSSIDV GASOLINE rILrERED KEROSENE,BARRELLED GAS OIL RE.PROCESSEO WITE WAX BARRLLED I SC14LL SWEA INTERMEDIATE REPROCESSED SLACK WAX HEAVY - FILTER PRESS R G STILL AS OIL AGIATORS DI ,STI - 1 DISTILLATE P S , TING OILS GAS OIL AUTO R.W.D, STILLLUBRICATING OILS. RAW WAY LUBRICATING DIST DISTILLATE F O ID FUEL OIL STORAGESTIE CENTRIFUGE P USTILLSIISAE HEAWO I M TN PETROLATUMSTOA iU AGITATORS BLEOING TANK% EXCESS OFRESIDUUM NOT FILTERED STEAM STILL FUEL OIL PROSSED FOR CYLINDER STOCK V IWAX FREES NAPHTHA RE-USED OIL CYLINDER FINISHEO LUBRICATING OILS _ ,, - " ,,,! --r" +.++ +_ - .2nz ~ iL~3-+ Ica- -LA-t c~ iTORAGE M [To face page 29] FINISHED KVI . '~a~eE~i~ ga4u~m~3p (P( USES OF METHANOL INDUSTRIAL SOLVENT PAINT AND VARNISH INDUSTRY I I I I PAINT AND VEHICLE IN 5OLVENT OF SOLVENT I VARNISH I SHELLAC FOR MIXOTURE FO I REMOVERS VARNISHES ALCOHOLGU VARIOUSGU CELLULOSE ACETATE AND NITRATE INDUSTRY PROCESSING SOLVENT PHOTOGRA- I I PHIC FILMS ARTIFICIAL PYROXYLIN CELLULOID AND PLATES LEATHER PLASTICS ARTICLES NON-SCATTER- ABLE GLASS I VEHICLE-SOLVENT I I I I I CEMENLULOID OPES I LACQUERS IENAMEL STAIN3 I RAW MATERIAL IN MANUFACTURING CHEMICAL PRODUCTS METIYL ACETATE, USED IN EX- TRACTS, PER- FUMERY AND AS SOLVENT I METHYLAL, USED IN MED- ICINE,PERFUM- ERY, ORGANIC SYNTHESIS AND AS SOLVENT I I METHYL- - METHYL NAPHTHO- BROMIDE LATE, USED USED IN IN ORGANIC PERFUMERY SYNTHESIS METHYL FORMATE. IODIDETHYL IODIDE,. USED IN USED IN ORGANIC MEDICINE SYNTHESIS I M ETHYL ANILINE, USED IN ORGANICG SYNTHESIS METHYL CHLORIDE, USED IN MEDICINE AND RE- FRIGERATION METHYL-p- AMINOPHENOL USED IN ORGANIC SYNTHESIS AND AS PHOTO- GRAPHIC DEVELOPER I I I O1METHYL-O.- DIMETHYL- DIMETHYL- NAPHTHYL- AMINOAZO- ANILINE, AMINE,U5ED BENZENE, USED IN IN qRGANIC 'USED IN ORGANIC SYNTHESIS MEDICINE SYNTHESIS I FORMAL CHEMICAL I USED IN ORGI PROCESSES DYE M'FR; PH AND KETONE I RESINS AND RUBBER GOOC PURIFICATION1 TANNING: IN OFORGANIC AGENT PHY;DISINFE' COMPOUND AGENT SERVATIVE F ANATOMICAL AND PRODUCT METHYLENET I METHYL ANTHRANILATE, USED IN PERFUMES METHYL CHLORO- SULFONATE, USED IN CHEMICAL WARFARE METHYL GALLATE, USED IN MEDICINE I DIMETHYL- SULFATE, USED AS METHYLATING AGENT FOR AMINESAND PHENOLS LDEHYDE ANIC SYNTHESIS: HENOL, CRESOL SYNTHETIC LACQUERS; DS; LEATHER KS; PHOTOGRA- CTING; PRE- OR ADHESIVES; SPECIMENS, 'ION OF HEXA- TETRAMINE. METHYL- ANTHRA- QUINONE, USED IN ORGANIC SYNTHESIS METHYL- CINNAMATE, USED IN PER- FUM ES, FLAV- OR5 AND CON- FECTIONERY METHYL- SALICYLATE, USED IN MEDICINE, LINIMENTS EXTRACTS FLAVORS AND CONFECTIONARY MISCELLANEOUS APPLICATIONS I I METHYL AUTOMOTIVE BENZOATE, INDUSTRY USED IM PERFUMERY I I COMPOSITE IANTI- MOTOR FREEZE M I IFUELS MIXTURES METHYL- DICHLOR- ARSINE, USED IN CHEMICAL WARFARE I I DIMETHYL- ACETAL. USED IN MEDICINE AND ORGANIC SYNTHESIS DENATURANT IN METHYLATED SPIRITS I I DIMETHYL:- DIMETHYL- TRITHIOCAR- SULFIDE, BONATE USED IN USED IN ORGANIG CHEMICAL SYNTHESIS WARFARE USED WITH ACETONE AND ACETIC ACID FOR FROSTING CELLULOID ARTICLES DYEING STRAW HAT5. I ANALYSIS I I DETECT DETECTING SALICYLIC BORATE5 ACID SEPARATING AR3EN'C AND A?TIMONY STOCK SOLU- TION5 OF PHOTOGRA- PHIC DE- VELOPERS TO PREVENT PRECIPI- TATION OF CHEMICALS IILLUMINANT AS A CON- STITUENT OF SPOTTING FLUIDS IN GARMENT CLEANING tTo face page 57] I a I a /!0f I I IFUEL' I GENERAL I FUEI UTILITY RAW MATERIAL IN I CHEMICAL PROCESSESI R0/C~POOSS I MAN/NUFACIR OFESTERS HEA T LIGHT POWER INi IN IN mp"dwfi- . A/ l loofo/oo O//CA01..o I A/h/i .4b ,oo-i;/-e rHE HOSPITAL THE CHEMICAL THE HOME 1N 4 C-thOl Z,n// LA 80RATORY ..... /IA/o,,o,Ioo,oo lkwnrrMIo lsl 0C44dkP/0 ooo,,e,M,-Co~oI /1 OR C/e"L TO ETHYLAL0/C/IOR-RETrLeElHYL EHYL ETHYL CTCL E/ ETHL TL ETHCL EETHL TYI /C CT //nTL PRCPTT/0R A//OI0//IRC ~ M S E L N O S AEO O/N ATSPI OXIDIZING PROCESSES Iemmfc/A//PR/OCI-5 I/lAE//N!V/"T1;M/LL" CA RMONRUAOYER NONf FREEZIN6 PRESERVATIVE ~ /C40 I II I[ OUTION Ak4oAoi&YUOdfo- ' /0/ OCNZ/i Ckp.L SOD UN"yCy'O-"' 'THY[ T A 1A c r l - - - - 1 1 0 0 t p - r,S 0 4 D C I D D /09o0,5c RI/I/Au cd~mr p~r~ ,o0Z/o//ooo O0ORAON4/I0 /9/IR A// I I I I I I I I LEVELS/OA E/ACI0/AI / I II rOSy" OLVE,T11 ON"ITROCELLU/OSE %IL NSOLVE/CTAIR SOAP SO/VNTCO, ESETAL 00/0 I o~ IL III~~Yed Akoh,h M, -A-A- or lh.rhno mPr'~dlndslnJ koh is-d;.the-f--VE th f P4 PATENT rrmtVL. CAL/A- S WATER S LIC/OR RN' CRO y/SOI OsCZLLC ONE//AC O/O 4//OAAAC SE L AN//LA LEMO/IRO $CI R JASMINE RAY RG R I/S 8//APURLREDAjyj/ASS4OS0/ARE/O_- P APERSALCOHOL PLASTICS PW/ER C&NE/ITO VARISI/CRI$CSISHESk T SOP S 0- CAA&B".IH IO /soLVENTFoR SCELLA NEOLS PURPOSESf 4 14 4 4 4 Aohol /i/00'05C Mc/M/4 OF TIC//RES S/,OhO MEM. GAS4 "T4M4ALI4ERAFRC,14441414, 4 t POLSMS ANfL SILK HIl ETMN6'NEr [.-Ic 7rrh OR L r F IE// j- I.XA OF 0E fPnnA L A117[ NAPES MO/AuoESgMANTELMMOIL/INEATAVIAANPT S FLUXES,,_L AV I 4 4 OT/RO RE/N /AlPS P/LE 5/AMPR V/NO NTS /OXS £1/OR /ATO NTO I/'S ~JELL0Y/ I I I I VOL VNr TOEI/IS P/IPSES =12T, 1/1/00ur~orur, of 6mm4I SOLTIOFN/NPRVSI &Iu /i/ MIWICALS SOLvem r RL VNlwxsj L RCo1wnA ow soLvENT IN cRTsrALUIZAnoNpRoctr&,s 1 1 1 4 4 L,,, II K-i hi P O N $77sCCRv POSTAPKI IO L _ [ I1 S L VrEI LKALOID), mrmAaj ACID Olt. EN, E M'NE REF/ AFE ILK OR IIOI O CARDS M / TOUENE CASCARA Jf/NA VLERUM R CYNIM AvlffRlSINOMIN/ 4 ft"11AL WI/7AN ISlAt"~n Oll- OXALIC CurtLERY WLRY 0/T 0AO/R ACID (NE/ON/N AIR/Il/RI I IWA TCHES OCA O/R OIll EII IIIZO IID MR.I N-IE [To face page 58] NOMENCLATURE OF SATURATED HYDROCARBONS 25 Nomenclature of Saturated Hydrocarbons.-Select the longest chain of carbon atoms in the molecule and number the carbon atoms. Consider the side chains as substituents. For example, 1 2 3 4 5 6 CH3-CH-CH2-CH-CH2 - CH3 CH3 C2H5 2-methyl-4-ethyl hexane. The table on page 26 includes a few normal hydrocarbons and the corresponding monovalent radicals. From the table we conclude the following: 1. Every hydrocarbon in this series is saturated (single bonds). 2. The name of each hydrocarbon ends in ane. 3. The hydrocarbons from CH4 to C4H10 are gases, from C5 to C16, liquids at ordinary temperatures, and from C17, solids. 4. The melting- and boiling-points increase with the increase in molecular weight. 5. The difference between any two consecutive members in this series is CH2. (Whenever we have a series of compounds where the difference between any two consecutive members is CH2, we get what is known as a homologous series. The word " homologue " sig- nifies " a member of the series." Homologous series are frequently met with in organic chemistry, and we shall refer to them repeat- edly. The great value in the study of these homologous series lies in the fact that members of such a series are really members of the same family, and, therefore, show strong family resemblances; or, to speak in terms of chemistry, strong chemical resemblances. This does not mean that the members of an homologous series are exactly alike chemically; but it does mean that they have certain common characteristics which distinguish them from 6ther classes of compounds.) 6. Their type formula may be represented algebraically by CnH2n+2. 7. The names of the radicals end in " yl," the suffix " ane " of the hydrocarbon being changed to " yl " (methane -> methyl). 8. The type formula for radicals is CnH2n+l (monovalent.) 9. The paraffins are known as " alkanes"; hence the group is S USES OF FORMALDEHYDE I DIRECT INDUSTRIAL APPLICATIONS ILEATHER INDUSTRYI LoE ,.iN PRESERVING [jZEj [ I"'J" ITEXTILE INDSTRYI ,,,TTU I 1OSITU ENT OF I IENT OF I STIFFENINGI I GLOSSING I AGENTS I IAGENTS I AW MATERIAL MANUFACTURIF IEMICAL PRODU I R CH IN I DYE INDUSTRY I IN NG JCTS SYNTHETIC RESINS I APPLICATIONS IN DISINFECTION ETC. DISINFECTANT I III 1IIII o 1 1o P PHENOL-I [ ,-I -PER SE WTIHWITH WITH BTUR UOISE CHROME NAHT-AEN WOL IFOR LE I FRAL R L R LE OR A INORGANIC 1 TALIPHATIC AROMATIC CAR5OHY- IT N BLUE GREEN ER ES DERIVATIVES TVES ORATES o -IINGHISFNG OFLCN[[AR- ACETONE" I T DOMESTICJ ON( GRAIN ON IGTAI EO SILK AND I LOADING METHYL ACRIDiNE IFORMALDEl IFG AE -IIFOME-I ILEE-FORI r KI SHIDES SKIS COTTOL[ HYDE HYDE HYDE REFRIGERAT°RSJ POTATO BI,S. CUPBOARDS I A5 RUBBER I , ISCELLANEOUS5 SINKS CELAR RuRUEIIJNcREASING1SELAEO INDUSTRY MANUFAO COAGULAT- TURING ING ACCELER- RUBBER I ATORS I ILATEX PROOFINI PAPER FASTNESS TRIPPING OF SSTANI I COLORs I TIVE DYES CELLULOSE INDUSTRY I (WITH, IHYDE-I INAO) I CjOSE: I I REDUCING PHOTOGRAPHIC AGENT INDUSTRY RECOVERING MANUFAC- HARENIN ONSTTUEN TONING INe PHONO- I AGENT FOR DEVELOP ELATO- GOLAND TURING GRAPHIC ILVER IR IPHOTOGRA I CMLORIDE RECODS ILVER MIRRORS PLATES QUNONE PAER I"WATER-PROOFING" STRAW HATS I I I I SDIAMINOD- PARAFORIAL- HEXAPMETYLEN ANHYDROFOR- N TANEI DEHYDE, TETRAMINE, tMALDEHYDE SEDAS RUBBE USED IN USED IN MEDCINE ANILINE, USD ACCELERATOR DII5NFECTING NA5 RUBER AS RUBBER AND IN MANU- AND INCHEMICAL ACCELERATOR ACCELERATOR FACTUREOFDYEI SYNTHESIS MISCELLANEOUS HARDENING I PRESERVING TUENT SMICRO- I ANATOMICAL I OF IPREPARA-I PIE I FMBALMIN s I ISPECIMENS I 5YNTAN* USED IN TANNING I I FUMIGATING IN SICK ROOMS WHITEWASH I ~ I IMT- .. II~I REATMENT OF RIOUS GRAINSI FOR SMUT TREATMENT OF SOIL FOR VEGETABLES IN CASE OF ROOT KNOT TREATING OLD I PRAING SOIL IN GREEN1 STABLES. PIG HOUSES AND PENS. CHICKEN COLD FRAMES ICOUPS ETC I~II, , ICLEANING CONTAINERS ,,I , l ~ IAND EUIP-I TUB AND AND OUI OTS INFECTED MOUTH O wJOINUTSIWOUNDS WA CAVITIES AS PHARMAY 3KIN DISEA5PC5 POMRIASIS AND USED AS USED IN I USED AS ASAN ANTI URNARYlI SK, . I LOCAL I SEPTICUR- ANT SEPTICI IDAEE I IANTICPT LDRESIG HELMITOL,I I SOFoR I ITANNOFOR,l VEROFOR. IUEOAS U IFOMALE-I IUSEDAS I IUSED FOR URINARY I IHYDE-SOAP IINTESTINALI CLENSINGAND FECTANT SOLUTION IASTRINGENTI DI5NFECTIM [To face page 74] USES OF ACETONE SOLVENT I so ^5 A I GARMENT I AC CLEANING MOST DISSO MATE VOLu COUPLE," OR 5POTNG PRE COMMON FLUIDS SOLVENT,TO CONTAINING COMBINE TWO ACETNE ARE OR MORE USED TO RE- IMMISCIBLE MOVE VARNISH SOLVENTS STAINS I USED WITH ITETIRAPOLE AND OTHER LIQUID SOAPS I k SOLVENT FOR TYLENE. IT IS THE T ECONOMICAL, OLVING APPROXI- ELY Z5 x ITS OWN ME AT ORDINARY PERATURE AND SURE I I I NZYLIOINI BROMOFORM, CHLORBUTAN ACETONE, USED IN I I A LOCAL USED IN I MEDICINE I ANESTHETIC ORGANIC AND ORGANICI AND SYNTHESIS PREPARATIONS ANTISEPTIC I I I INDIGO, IODOFOtRM, IONONE, USED IN USED USED IN wYE IN PERFUME INDUSTRY MEDICINE INDUSTRY I I I CHLOROACE- CHLOROORM DIACETONE i TONE, IA SOLVENT ALCOHOL, USED IN AND A ISOLVENT ORGANIC ANESTHETIC SYNTHESIS ESTERS ISOPROPYL MESITYL ISOPRENE, ALCOHOL, OXIDE, UMFR. ED IN USED IN USED IN MFR. OF SYNTHETIC ORGANIC SYN- CELLULOSE RUBBER THESIS AND ACETATE MEDICINE SOLVENTS I I PINACONE, SULPHON- I USED IN I METHANE. SYNTHETIC MFR. OF A HYPNOTIC RESINS SYNTHETIC AND PLASTICS RUBBER SEDATIVE MISCELLANEOUS I I APPLICATIONS IMEDICINE I ICHEMICAL ANALYSIS I A A MILD TO DETERMINE ALTERATIVE AS AVE RESIN CON- EXAMINATION MINTIC I RUBBER TREATMENT I ACETONE SATURATED OF WITH 0S, Is USED IN PURULENT COAL EXTRACTIONS WOUNDS AND SEPARATION OF UNSATURATED HYDRO- CARBONS FROM SATURATED BODIES I I I PAINT AND VARNISHI CHEMICAL I CELLULOSE ACETATE INDUSTRY PROCESSES AND NITRATE INDUSTRY I FL9 OF PAINT FOR NATURAL OR VARNISH AND SYNTHETIC DESICCATION AGENT REMOVERS I RESINS AGENT I I ARTIFICIAL ARTIFICIA CELLULOI I TO" ROXYIl SMoEL SOLVENT IN wn[ L Ij j GRAPHICc ITUMIOUS FCATO LK LEATHER ARTICLES FILMS PLASTICS WDER PAINTS SELECTIVEIO TNT. AND SOLVENT I ITEROMA;Wi I IA.IMPUn I VEHICLE-SOLVENT I I I I I JAUTOMOTIVE INDUSTRY ROSULFITE DENATURANT ATIFICIAL I OF ACETONE FOR ETHYL SEASONING ARE USED IN ALCOHOL OF WOOD OTOGRAPHY CONSTITUENT USED AS A OF CARBON- BLENDING REMOVERS, AGENT IN TO REMOVE COMPOSITE CARBON FROM MOTOR RIFICATION FREEZING OF CYLINDERS OF FUELS U OFCRUDE Mct INTERNAL-RUBBER COMBUSTION ENGINES RAW MATERIAL N I CHEMICAL MANUFACTURE [To face page 781 I A -t USES OF ACETIC ACID RAW MATERIAL IN MANUFACTURING CHEMICAL PRODUCTS DIRECT INDUSTRIAL APPLICATIONS PAINT AND VARNISH4 i INDUSTRYI nN Fl BR E LEAD IAACASIT Oylro JI T URTR AXI CONS TOEN1CT MENENTOD crslce T uEPINTIAR 5i, KCCLTO XHORTCOETTON GARMENT CLEANING INDUSTRY T, Mt~ IP i n EIJ _ ; T I ,T Z RU'.)E %Ff FRM 'TEX LEATHER ER OIMING RE NNISOLVENT I AM IND RENS LJN FATUMI1U AMMruonIuM IAEAE,TD CETAE. IWATERRAOA-II USED t INCcoTAAGI IMEDICINE AND 1ORDAT IN A CREMICAL ILW i61REAGENT ACATE. I ACETATE,I USED IN I T iDED IN TEXTILE ITAPTEIEI INDTTR I N FERRIC IBAIC ERRIC TCEAR,USD CETREUTET IN MEDICINE I In MEDICINE AND TEXTILE I ANT TEXTILE ISIAAITTA INUSTRY RAS C LEADI MANGANESE ITETPE UEDI ACETAT. SILl' ANTD YEA-I TEXTILE AlFPT ATING INDUSTRY ACEATE AC ;,E% MTNT, USED IN MORDANTS F:T,' A~CENIC ENACT ADXUAAC INDOSARY I MISCELLANEOUS I APPLICATIONS I I AZ.1 L~ MEDICINE I CHEMICAL ANALYSIS BARIUM CALCUM AMINDUCETC AMAGRA*LIC CACODALIC CITNXL D ILurF-ACETIC! IGLACIALACETIC 1 11N ACID, UE C ACID A110 CUSED IN ORGAIIC AENI5 AiETATE, ACETATE. A. UED I AI. I MEDICINE ASLO IN USED A[ 1,USEA A, iTEIC MAE INTn 5 I ORGANIC AS C EL N 15 - IT ACETOE AN D XS MEDICINE STNT ESIS S TE S I IRNEAEGENTF I NH INRT LY I CAUSTIC IN SGIl REAGENT ACETIC ACID ....... ITENALYr TREDUCEI L AFI'ECTIDNS IADINE ETC DETTA ADLACE C EAICAL ANAFAEUT13 T I OR A I DA HALOGENATED GERMICIDE, LOWS TESTE CAPPER AILCCRPET ACID. ASED XEUD. USLCOLS WART CONDC CRECT. AE hE. 5O IORGAIC IA CTE TEAXRRAXE ININSECT IN PAIT IG- S N ESIS REAGENTMEDttNEBY CIETETILERTENTX.T.INSET- I NNEX IA~iln SLEN RET FT'TZ VA EN TaS J ENS~ PLG ACETAT ANINLYTINCC ASASDEACNLLOCALTE TASEX WE A S 0 C ,C ANDCERAMIC DXANDTEA TENEMAFOR ASTIEN PAIt:A R DE RUTIN I uD FIN INDUSTRIES ATIE INDURTR NDSTYELIEFPT IIFLAMMA 1111 HALOGEATED PAS A~5TNESGRIIERNWRMTN EA CP COMPOUNDS OOEN USED N ACEATEUST j j J,,, MEDICINE INMEDICINE 7CET 7 ION ANNIJ AND TEOTILE ADANAL TICACY I CR UNN INDUST CEIS5TRA BROMIDE, CALORIDE XOIIE ACE IC AiD 0flTPl XC A N3 USED IN USED IN USED IN USED T E A XXXC A CAXYN ORGANIC ORGANIC ANGAN C ORGAN CTURCDAN TANTAEXIT SYNTRESIX TYN ALT S Li AG N1 MEXCUOUT CTT.UE ACETAT, ATDARXIUM XCLX USED IN AXENT AND MIEDICINE IN MEDICINE ACETIC XCIX, AETCACD AXDIN ORGU DREIE nMA RVETN IUF IC SANTALSIX CTTE 1 CEAD PEEVI EMN RP OIIIO ANT MEDICINE EJCn I5E TV tlL I RA OC00 'C*N ACETTE, SE AETRE. IN MADICINE USED IN ISELNO CHMt RPOR AIVN A5N ANATTL NLRICAC ICLAEU CCTISTAYR CEISTAT COMPOUNDS I5h PT~ CATAI-YST LAUNDRY TINDUTRY PROIN G PIPDYMGTE7G AU UNNAL LEAD AIRSEATEC 1G EUNRGCICING PATENT LUTNE A ND ISOrEUR AAL SSN h LT K PROCE StTQ REAGNT - - ~I " " L , ,- I --- - ---- I 8EYBAGE IN MILK I PODC- ZINC ACE TE. ECTT,NICIDE. ACETIC USED IN MEIC AnINAIE. ACETIN. ?RESERVING WOOD USED IN LINE ANT AS USED IT USED IN AND TEXTILE INDSTRY ORGANIC PTESETGATIVE ORGATRIC EAPLGSTIO ANEST FUN TAO, STOTAEFTIS I LEANINU I FROTING I PREPARING TRTTFT FU FIXTIDY AEUT RRI CElic ULG,DLELCU.I o CIDER GE L\COTU C ARATD j,,,, RIC'FS RACCET TNEGRNG NESIR hnDEICT IN~ IKETON E.U5ED ACFTO A AIi. LVFNTAN TIDINE. uD INSA InoRG~~~~~FliINU .1 SE ICTAS IDli;Em PEDCPI " TA AEN INZYLRGAE TM C E CLUOE A T TYIIESIS MEDICINE PERFUMERY TnM l O i1 [11111] Pii- E IN GNE USED IN MF5YCTNEAN5MED4ANE AX NgLISED rN NMLUTI NES ND ADD POERA AETAMES CTC TAFV1E F""''1NE DICTL- CE CDRONO PTEME LCACS.RCETOMT EANIIN. TAIGE INDOFDRM ,,,,j,,,,,,,,,,, NADRN N USED IN USED IN USDI DERAN C NA F 1 RTFUMLAT EDICINE MEDICINE FXUROTA LENiL [,,,,,,,,,,,,, M I ,,,,,,J EFUFT TE A CETATE CTE I ITAE USDAI USED IN L....CT PRUMSI IIE,- ITlR~ING~I PERFUMES~ EXTRACTS AN ETERA EFUE NEDAE-REDMLIT OANIC USED IMP INI IRADXINACIITCNRINXLI. ACETATE,IIAETER'I I XEA In IXTED bI [To faoe page 85] I I TEXTILE I INDU5TRYJI I COAL PRODUCTS CHART Compiled by Professor ALEXANDER LOWY, University of Pittsburgh Black Type indicales Products direct/ ob/ained from Coal. ,ooo .c. ICOAL GASj LIGHT OIL 3-4gal Fuel G I I umnatng Gas] Benzene ( Benzol), Motor Fuel Gas Cyanogen IlluminatingGasToluene (Toluol). fuels, - Xylenes (Xylols), ' Solvents, Sulfocyanides Ferrocyanides Solvent Naphtha, etc. Naphthalene, etc. 70-120 /bs Alkali Cyanides Ferricyanides Prussian Blue / 71ht 0l' "andIddle Oil COAL Dehydraled and s-isl MIDDLE OR CARBOLIC I7000r 21/00t selow/700or2Oo or rTar OR NAPHTHALENE OIL 2300or 240 o-3Z1 . ... I, / on OAL Destruce Dishllo/io Rod 71pi'/e ,o,/eI' P'ru r P,repared by ('f r,1a/ tfe//,o. Bituminous aaboull00° TAR] /00-/00 D/sil/led Ammonium Aqua Anhydrous Liquid Sulfate I Ammonia Ammonia Ammonia Arnmonium salts, as am- Nitric Acid monium nitrate, sulfate Am,nes. etc.. chloride, carbonate,i- Refrigeration carbonate, persulfate, eicI I Refrigeration o ofar LIGHT OIL Crudearbo Wood Preservative CrudeCrude Carbolic Acd I Acid, Antiseptics Naphthalene Disinfectants Pheno es r Refined NaphthalenePheno PhenolCresylic Acid Moth balls.Flakes, etc. Phenol Acid Plastics, Disinfectants. Phthalic Nitro Naphthalene See und (BEakelite (Lysol, Creohn Anhydride naphthalene Su!fonic Acids "Middle 0 Picric Acid, Saicylates. Remano Phenacidophetin, Aspiran. Phenol- Anthra- Explosives, Naphthols. Dye intermediates Methyl Salicvlate ndicatdr, phthalei quinone Napithylamine Dyestuffs, Developers, Salol Phthatives Isectcdesetc Explosives. Dyestuffs. amide- Dyes. etc etc. Preservatives, etc Flavoring Intemediats'. substances, IAnthraniliC aid er si Perfumes etc Ac.d II I I I I Crude Benzene Pyridine Heavy Naphtha ISolvent NaphthaJ Crude Crude Toluene Beno Acid Crude Benzol Carbolic Acid Crude Toluol Benzene Denaturant Syro-et Resn Xylenes Phenol Cresols Toluene Food Preservalives IBenzene II ' Coornaroine Res,wlnToluene Haiogenated Nitro- Maleic enzene Dye intermea!ates See under Nitro- Toluene Sulforiic Benzene berizene acid suifonic acd and Dyestuffs Mddle O/" Toluenes Acids Dyestuffs, Dye Intermediates Phenol Dye intermediates Explosives Toluidines f3enzaldehyde At septics Insecticides Developers, etc See under and Oestuffs Saha ri et Anine n Dye Intermediates Fav-inc I AniindleOand Dyestuffs substances Aniline Salts Dimethy Quinone Phenyl Drugs, Dye Inter perfus t aniline hydrazine rnediates, Dyestufds Dr!ugs etc Dye Intt mediaes [Iit lrn1I Ant ipyrinel yied[9tgra,icf Copyr/iht /9 3 by 0 Van lt/t andCo "Creosote Oil used for wood preser- vation is generally made up from the " M:ddle" " Heavy"and "Anthracene Oil" fractions. " REFINED COAL TAR" This is coal tar from which water and the light oil have been removed, or a mixture of any grade of pitch with any of the heavy tar distillates. Uses:- Coating ironand steel pipes, roofing paper, paints, paving mate- rials, insulation, water proofing,etc. Metallurgical. Retort carbon, I Foundry, Coke breeze, COKE Domestic fuel, SElectrodes. etc. Calciuml arborundum Graphite Carbdde ' I Abrasives Lubricants, Crucibles, um Acetylene Electrodes, mide I etc. S Acetaldehyde Acetic Acid I Acetone 26 SATURATED HYDROCARBONS OR PARAFFINS PARAFFIN SERIES * Boiling- Point -164 - 89.3 - 44.1 - 0.1 + 36.3 + 68.9 + 98.2 +125.8 +149.5 +173 +194.5 +214.5 +234 +252.5 +270.5 +287.5 +303 Formula CH4 C2H6 C31Hs C4H,o C6H14 CsH121 C7H16 C81118 CsHls C9H20 CloH22 CI11124 C12H26 C13H28 Ci4H3o C1511H32 C16H34 C1711H36 Name Methane Ethane Propane Butane Pentane Hexane Heptane Octane Nonane Decane Undecane Dodecane Tridecane Tetradecane Pentadecane Hexadecane Heptadecane Hexacontane Alkane * A fairly complete table is given at this point to illustrate to what extent a series has been investigated. In the other portions of the book where tables will be given, only the first few members of a series will be included. Melting- Point -184 -172 -135 -130 - 94 - 97 - 56 - 51 - 32 - 26.5 - 12 - 6.2 + 5.5 + 10 + 19 + 22.5 +101 Name of Mono- valent Radical Methyl Ethyl Propyl Butyl Amyl or Pentyl Hexyl Heptyl Octyl Nonyl Decyl Undecyl Dodecyl Tridecyl Tetradecyl Pentadecyl Hexadecyl Heptadecyl Hexacontyl Alkyl CnH2n + 2 Formula of Radical CH3 C2H, C3H7 C4H9 CsH, C6H13 C7H15 CsH17 C9H19 CloH21 C,H23 C111H25 C1311H27 C14H29 C5H31 C16133 C1711H35 C 60oH121 PETROLEUM OR CRUDE OIL spoken of as an " alkyl group." The alkyl group is represented by the letter " R." Lower members have anesthetic properties while the higher ones beginning with C12 have no physiological effects. General Methods of Preparation. R ICOONa + NaO H -* RH + Na2CO3 CH3COONa + NaOH - CH4 + Na2CO3 2. RIX + 2Na + X R R-R + 2NaX C2H51 + 2Na + IC2HB -5 C4H1 o + 2NaI 3. RX + HIH -RH+HX C2H5Br + H2 -* C2H + HBr (X refers to halogens.) General Properties.-The paraffins are insoluble in, and lighter than water, and soluble in alcohol, ether, chloroform, ben- zene, etc. As a rule, their odor is rather pleasant. They are flammable. General Chemical Properties.-All the paraffins are very stable and inactive. At ordinary temperature they are not acted upon by nitric, sulfuric, hydrochloric or chromic acids, or sodium hydroxide. Chlorine reacts in sunlight to form substitution products. Bromine reacts less readily. Iodine does not react at all. (The student will be puzzled at this point to explain how the various iodide compounds used in the Wurtz synthesis for par- affins are prepared. We must refer him to the chapters on unsat- urated hydrocarbons-p. 33-and alcohols-p. 56-for an answer.) Petroleum or Crude Oil.-The history of the development of the petroleum industry in the United States is instructive. The Indians in Western Pennsylvania first discovered oil floating on surface waters. By them it was used as a remedy for all physical ills. In the middle of the last century, it occurred to a Colonel Drake that, since oil came to the surface of springs, it was probably present in much larger quantities beneath the earth's surface. He thereupon proceeded to drill a well near Oil Creek, Pa. and, before he had dug 100 feet, oil came to the surface in such quan- tities that all of it could not be collected. 28 SATURATED HYDROCARBONS OR PARAFFINS The industrial importance of petroleum is recognized the world over. Coal alone takes precedence over it as a fuel. It is largely, though not entirely, made up of hydrocarbons, but not all the hydrocarbons belong to the paraffin series-the series we have studied in the present chapter. Some of them belong to a type of hydrocarbons with which we shall become acquainted in the next chapter. Petroleum is found in many parts of the world, but more par- ticularly in the United States (Pennsylvania, California and Texas), Mexico, Russia (the Baku region), Roumania and Persia. The natural product is usually dark in color, with a characteristic odor, and with a specific gravity that is usually, but not always, less than water. It may be regarded as a mixture of substances, mostly hydrocarbons. The various products derived from petroleum are obtained by means of fractional distillation, the first fraction consisting of products which pass into the distillate below 1500, the second, those that pass over between 1500-3000, and the third, those which pass over above 300'. Each fraction is again redistilled and divided into more fractions, ultimately yielding substances of commercial value. In many refineries the division into fractions is based on specific gravity. The light oils (up to 1500) include petroleum ether, benzine, gasoline and ligroin; the illuminating oils (from 1500-3000) include kerosene; and the lubricating oils (3000 and up) include spindle, machine and cylinder oils, etc. In addition, many products of commercial value are obtained, such as vaseline, paraffin, etc.; and the tar residue in the still is used in road-making, artificial asphalt, roofing, etc. If the temperature is high enough, petroleum coke in the place of tar is formed. Due to its high purity, this coke finds extensive use in the manufacture of elec- trodes. Commercially, the most important product obtained from petroleum is gasoline, a mixture of hydrocarbons of relatively low molecular weight, such as pentane, hexane, heptane, etc. The process of purification consists of treating the gasoline with sul- furic acid-incidentally one of the most important uses for this acid-whereby many objectionable impurities are removed; the sulfuric acid in turn being removed by washing with water and subsequently with sodium hydroxide solution. READING REFERENCES By a careful study of the physico-chemical reactions involved (such as temperature and pressure), American chemists have developed methods of increasing the yield of gasoline. The " cracking " process, used so extensively to-day, consists in break- ing up the more complex into the simpler hydrocarbons; for example, C18H38 -* C10H22 + C7H16 + C kerosene gasoline carbon Albolene, nujol and petrolatum are petroleum products used extensively in medicine as intestinal lubricants, and, in pharmacy, as bases for ointments, salves, etc. (Times have changed, indeed. Less than thirty years ago, kero- sene cost more than gasoline; the latter, in fact, was regarded little more than a nuisance. To-day it would be hard to conceive of many substances more valuable in commerce than gasoline. Wherever minute quantities of the fuel can be found, it is care- fully extracted. Even the small amount found in natural gas is extracted and recovered. Gasoline obtained in this way from natural gas goes under the name of " casinghead " gasoline.) The chart facing p. 29 outlines the salient features of petro- leum refining at a typical plant and names the important com- mercial products obtained. READING REFERENCES TILDEN-Chemical Invention and Discovery in the Twentieth Century. (1916), chap. 14 (Petrol). CALDWELL AND SLossoN-Science Remaking the World. (1923), pp. 12-47 (Gasolene as the World Power). RoGERs-Manual of Industrial Chemistry. (1921), pp. 588-633 (The Petroleum Industry). WESTCOTT-Handbook of Natural Gas. BELL-American Petrolum Refining. BACON AND HAMOR--American Fuels, Vol. II, Chapter XIII on Natural Gas. CHAPTER III UNSATURATED HYDROCARBONS OR OLEFINS AND ACETYLENES So far we have been dealing with hydrocarbons that are sat- urated. When bromine comes in contact with a hydrocarbon of the methane series, CnH2n+2, it can enter the compound by sub- stitution only, not by addition; that is, by eliminating one or more hydrogen atoms from the molecule and substituting other atoms, but not by adding an outside atom without any elimination. In this chapter we take up two series of unsaturated compounds, where, as we shall see, atoms can enter the molecule without others leaving it. One series is known as the olefins, CnH2,, characterized by H H C=C I I H H and the other, the acetylenes, CnH2n-2, characterized by H-C-C-H (The student must not draw the conclusion that because there is more than one bond between two atoms, the union between such atoms is correspondingly stronger. On the contrary, since bonds represent strains, the greater the number of bonds between any two carbon atoms, the greater the strain, and hence the greater the chemical reactivity of the compound; so that ethylene is more reactive than ethane and acetylene more than ethylene.) 1 I The instructor may illustrate these "strains" by the use of Kekulg models. Full scan of this foldout is at the end of this text 'XCESS "CESS ; : r AN INTRODUCTION TO ORGANIC CHEMISTRY PREPARATION OF ETHYLENE OLEFIN SERIES, CnH2n-ALKENES CH2 (hypothetical) Methylene C2H4 Ethylene or ethene C3H6 Propylene or propene C4H8 Butylene or butene C5H10 Amylene etc. (Compare with the paraffins, p. 26.) These compounds constitute an homologous series, just as the paraffins, for there is the same difference between any two con- secutive members-CH2; but it will be noticed that the corre- sponding olefins have two hydrogen atoms less than the paraffins. The simplest known member of the olefin series, ethylene, com- hines with chlorine to form an oil (C2H4C12); hence the name olefin (" oil-forming "). In naming these compounds, we change the ending ane of the paraffin containing the same number of carbon atoms into ylene or ene; e.g., C2H6 (ethane)-C2H4 (ethylene or ethene). We shall describe one member of this series, ethylene, in some detail, and the general characteristics of the other members can be gleaned from a study of this one. Preparation of Ethylene, C2H4.-One method is by the action of an alcoholic solution of sodium or potassium hydroxide on ethyl bromide, a method of preparation that gives us an insight into the structure of the compound: HH HH I alcoholic KOH I H-C-C- Br > CC + KBr + H20 RH_ HH If, instead of using an alcoholic solution of sodium or potassium hydroxide, we use an aqueous solution, ethyl alcohol, C2H5OH, is produced (p. 53). Another is to treat ethyl alcohol with a strong dehydrating agent, such as P205 or H2SO4. 32 UNSATURATED HYDROCARBONS OR OLEFINS IH H H H-C-C- OH -+ C=C + H20 I I I I HH HH (An alcohol contains an OH group; see p. 48.) (The ethylene used during the late war in the preparation of mustard gas (p. 184) was prepared by passing the vapor of ethyl alcohol over clay balls heated to 350-400'.) Also, by the action of sodium or zinc on ethylene bromide (dibromoethane): H H H-C-C-H - C2H4 + ZnBr2 Br Br +Zn (C2H4Br2 may be regarded as ethylene, C2H4, to which two bromine atoms have been added; or ethane, in which two of the hydrogens attached to different carbon atoms are replaced by bromine.) Properties.-Ethylene is a colorless gas with a sweetish odor. It burns with a smoky, luminous flame, and forms explosive mixtures with air. It is present in coal gas to the extent of 4-6 per cent, and is partially responsible for its luminosity. It is produced, therefore, in the destructive distillation of coal. Recently, Dr. Luckhardt, of the University of Chicago, has shown that ethylene is a powerful anesthetic and has even some advan- tages over nitrous oxide. Within the past year ethylene has also been introduced in California for coloring mature citrus fruits (oranges, lemons, etc.). The characteristic properties of ethylene are dependent upon the presence of a double bond, and therefore upon its unsaturated character.. It combines with halogen acids, with halogens, with hydrogen, with sulfuric acid, with hypochlorous acid, with ozone, etc.: PROPERTIES H H C-=C + HBr H H C2H4 + Br2 C2H4 + H2 H H -+ H-C-C-Br H H (Ethyl bromide or bromoethane) H H -- H-C-C-H Br Br (Ethylene bromide or dibromoethane) C2H6 (Ethane) H H C2H4 + H2SO4 --> C2H5 HSO4, C2H4 + HOCI (Hypochlorous acid) H H -* H-C-C-H Cl OH Ethylene chlorohydrin) I I H-C-C--H HO I HO 0 (Ethyl hydrogen sulfate) (Whenever a compound has a halogen atom attached to a carbon atom, and an OH group to another carbon atom, we speak of it as a " halohydrin "; hence chlorohydrin, as in the above.) H H C2H4 + 03 - H--C--C-H 0-0-0 (Ethylene ozonide) A test sometimes used for the detection of the double bond is based on the action of very dilute potassium permanganate; the violet color of the permanganate disappears, due to its decompo- sition. The reaction may be represented thus: C2H4 + H20 + 0 or 2(OH) -- CH2 .0H (KMnO4) CH2 - OH (Ethylene hydroxide or glycol) 34 UNSATURATED HYDROCARBONS OR OLEFINS (The student must clearly understand that C2H4 alone rep- resents the gas ethylene, but C2H4 may be present as a divalent group in a compound; for example, ethylene bromide, C2H4Br2.) HHH Higher homologues. C3H1, H-C-C=C I I H H (Propylene or propene) 4 3 2 1 C4Hs=(a) CH3 CH2 CH=CH2 (1-Butene or ethyl ethylene) 4 3 2 1 (b) CH3 - CH=CH CH3 (2-Butene or sym-dimethyl ethylene) 3 2 1 (c) CH3-C=CH2 (2-Methyl-l-propene or un- I sym-dimethyl ethylene) CH3 (In naming olefins, numbers are employed to indicate the posi- tion of the double bond; the number, denoting the unsaturated carbon atom which lies nearest to the end of the chain.) Sometimes the Greek letter A is used to denote the double bond, so that (a), (b) and (c) may also be written Al-Butene; A2-Butene; 2-Methyl-Al-propene. (The methods of preparation and properties are analogous to those given for ethylene.) ACETYLENE SERIES-CnH2n-2-ALKINES C2H2 Acetylene or ethine C3114 Propine or methyl acetylene C4H6 Butine or dimethyl acetylene or ethyl acetylene etc. These also constitute a homologous series. The members con- tain two hydrogen atoms less than the corresponding members of the olefins, or four hydrogen atoms less than the corresponding paraffins. They are named by changing the ane ending of the paraffins into ine, so that ethane, C216G, for example, becomes PREPARATION ethine, C2H2. This series is known as the acetylene series, for acetylene is the most important member. As before, we shall discuss a typical member in some detail. Acetylene, C2H2, has the formula H--C-C-H, which shows it to have a triple bond and therefore indicates that it is even more unsaturated than ethylene,' a view which is confirmed by a study of its reactions. Acetylene is an extremely reactive compound. Preparation.-One method is probably already familiar to the student. It is the action of water on calcium carbide: CaC2 + 2H20 --, C2H2 + Ca(OH)2 Another is similar to a method used under the olefins: H H H -C - C- H + alcoholic 2KOH S I_ .--> H-C C-H + 2KBr + 2H20 Br Br (Ethylene bromide or dibromoethane) So is the following: H H I I Br -C-C- Br -- C2H2 + 2ZnBr2 Br Br +Zn +Zn, (Acetylene tetrabromide or tetrabromoethane) Acetylene is a colorless gas. When mixed with air in a special type of burner, it burns with a very brilliant white light and is used for illuminating purposes. When burned it gives out a large amount of heat. This is made use of in the oxy-acetylene torch (for cutting steel, etc.) wherein acetylene, supplied under pressure, is burned in the presence of oxygen. The gas is apt to explode if stored under pressure, but can be safely handled if it is first dis- solved in acetone (as in " prestolite " tanks). Liquid acetylene is highly unstable and highly explosive. 'The instructor may illustrate this by the use of the Kekul models. 36 UNSATURATED HYDROCARBONS OR OLEFINS Properties.-Since acetylene is an unsaturated compound, it will form addition products (like ethylene), but since it is more unsaturated than ethylene, it can add to itself more atoms than C2H4. H H H HH HH I I +H2 I I +H2 I I C-C ---> C==C ---> H-C-C-H I I I I R H H H HH HH H-CC=-H + Br2 -- C=C + Br2 -- Br-C-C-Br I I I I Br Br Br Br (Acetylene dibromide (Acetylene tetrabromide or dibromoethylene) or tetrabromoethane) HH HH H-C=C-H + HBr -- H-C==C--Br + HBr -- H-C-C-Br H Br (Bromoethylene) (Ethylidene bromide) (CH2Br. CH2Br, ethylene bromide, or symmetrical dibromoethane, is isomeric with CH3. CHBr2, ethylidene bromide, or unsymmetrical dibromoethane.) When acetylene is passed over finely divided nickel, three molecules of it polymerize to form benzene: 3C2H2 -- C6H6 (Polymers are substances having the same percentage compo- sition, but different molecular weights. C2H2 and C6H6 have the same percentage of carbon and of hydrogen, but the molecular weight of acetylene is 26 and that of benzene is 78.) Acetylene combines with ammoniacal silver chloride or copper chloride solution to form metallic derivatives (acetylides): H H Ag Ag Cu Cu I I I I I I C C --. C-C or C-C (Silver a!etylide) (Copper acetylide) PROPERTIES 37 Many of them are highly unstable and explosive, particularly in the dry state. In fact, many of the explosions involving acety- lene are due to the formation of these acetylides. CaC2, C C, calcium carbide or calcium acetylide. Ca Higher homologues. C3H4, CH3 C CH (Propine or methyl acetylene) C4H6, (a) CH3. C- C CH3 (2-Butine or dimethyl acetylene) (b) C2H5C CH (1-Butine or ethyl acetylene) (The general properties correspond to those of acetylene, except that only the compounds with the structure -C-C--H can form acetylides.) (At this point review the nomenclature of hydrocarbons on the " Organic Type Formula " chart, p. 16.) Compounds containing two double bonds are isomeric with those containing one triple bond; for example, CH3-C=CH is isomeric with CH2=C--CH2. The name of a compound having one double bond ends in ene; a compound having two double bonds has the ending diene, e.g., CH2=C=CH2 is propadiene. The most important among the compounds containing two double bonds is isoprene CH2=C-CH=CH2 CH3 or 2-methyl-1,3-butadiene, which has been shown to be one of the decomposition products of caoutchouc (natural rubber), and which is obtained by the distillation of the latter. Isoprene itself (in presence of catalysts, as HCI, Na, etc.) has been polymerized back into a substance resembling caoutchouc, the resulting product showing some striking resemblances to natural rubber. The synthesis of rubber on an industrial scale, however, is a problem that still awaits solution. There seems to be little doubt in the minds of chemists that isop1rene, or some substance closely analo- 38 UNSATURATED HYDROCARBONS OR OLEFINS gous to it in structure, will prove to be the starting-point of such a synthesis. The diagram below makes clear some of the interconnections of compounds already discussed: Brq C2116 A H2 C2H4 A C2H2 C2H,Br Br2 CH2Br-C2Br SEthylene bromide SCH3 CHBr2 Ethylidene bromide 2 Br2 2 Zn C2H2Br4 READING REFERENCES 39 READING REFERENCES TILDEN-Chemical Discovery and Invention in the Twentieth Century. (1916), chap. 25 (Rubber). SADTLER-Chemistry of Familiar Things. (1915), chap. 20 (Rubber). SLossoN-Creative Chemistry. (1920), chap. 8 (The Race for Rubber). PORRITT-The Chemistry of Rubber. RoGERS-Manual of Industrial Chemistry. (1921), pp. 827-850 (Rubber and Allied Gums). POND-A Review of the Pioneer Work on the Synthesis of Rubber. Journal of the American Chemical Society, 36, 165 (1914). BRowN-Forest Products. (1919), chap. 19 (Rubber). ANoN-Ethylene as Anesthetic. Journal of the American Medical Asso- ciation, March 17, 1923, p. 765; May 19, 1923, p. 1440. WORKS BY THE SAME AUTHORS PUBLISHED BY D. VAN NOSTRAND COMPANY EIGHT WARREN STREET NEW YORK CITY BY ALEXANDER LOWY Organic Type Formulas. Two color chart. 5 x 8, paper leaflet. (See page facing 16.) $0.10. Wall Chart of Organic Type Formula. A Chart in two parts. Each mounted on linen, each 4 x 6 ft. With shade roller attachment in steel case, per set, $20.00. With sticks for hanging, per set, $10.00. Organic Type Reactions, Known by Their Origi- nator's Names. Two color chart, 54 x 81, 6 page paper leaf- let, $0.15. Coal Products Chart. 11 x 17, paper leaflet. (See page facing 199), $0.15. BY ALEXANDER LOWY and T. B. DOWNEY Study Questions in Elementary Organic Chemistry. 6 x 9, paper, 100 pages, $1.00. BY BENJAMIN HARROW Eminent Chemists of Our Times. Illustrated, 5 x8. 264pages. Cloth, $2.50. From Newton to Einstein. Changing conceptions of the universe. Second Edition, Revised and Enlarged. Portraits and illustrations, 4 x 7 , boards, 116 pages, $1.00. CHAPTER IV HALOGEN DERIVATIVES OF HYDROCARBONS WE have already observed that the action of chlorine on methane gives us the following substitution products: CH3C1, CH2C12, CHC13, CC14 (p. 19). It ought to be possible to pre- pare any one of these substances by employing the proper amount f chlorine. (Bromine is less reactive than chlorine. It produces analogous substitution products. Iodine does not react with methane.) It is found in practice, however, that a series of simul- taneous reactions occur, yielding a mixture of chlorides. (Men- tion may be made at this point of the many attempts to produce chloroform, CHCl3, on a commercial scale by the action of chlorine on methane; and also of methyl chloride, CH3C1, by a similar reaction. Methyl chloride can be easily hydrolyzed to methanol or wood alcohol, CH30H, and thus the synthetic methanol could then be prepared starting from natural gas, which contains methane. Research is being carried on at the present time along these lines.) Monohalogen Derivatives of the Paraffins.-An alkyl halide (or monohalogen derivative of a hydrocarbon, p. 43), may be regarded as a saturated hydrocarbon in which one of the hydrogens is replaced by a halogen (F, Cl, Br, I). The following will make this clear: CnH2n+2 CnH2n+l Group CnH2,n+IX (alkyl halide) Methane, CH3H Methyl Group, CH- Methyl chloride, CH3CI Ethane, C2HhH Ethyl Group, C2H1, Ethyl bromide, C2HLBr etc. etc. etc. Alkane, RH Alkyl Group, R Alkyl halide, RX (RX is the type formula for an alkyl halide.) GENERAL METHODS OF PREPARATION ALKYL HALIDES Chloride For-rom P. For- B. P. For- B.P. Chloride * Bromide Iodide mula C. mula CC. mula o C. Methyl CH3Cl -24 Methyl CH3Br 4.5 Methyl CH3I 43 Ethyl CsHsCl 12.5 Ethyl C2HSBr 38.4 Ethyl C2HsI 72 Propyl C3H7C1 46.5 Propyl C3H7Br 71 Propyl C3H7I 102 Isopropyl C3HC1l 36.5 Isopropyl C3H7Br 59 Isopropyl C3H,I 89 n-Butyl * C4H9C1 77.5 n-Butyl C4H9Br 101 n-Butyl C4H,I 129 etc. etc. etc. * n- is the abbreviation for " normal." In each group the specific gravities decrease as the molecular weights increase. The specific gravity increases as we pass from a certain alkyl chloride to the bromide and in turn to the iodide having the same alkyl group. These halides are insoluble in water but soluble in ether, ben- zene and alcohol. The halides are generally colorless liquids with a pleasant odor. On standing, they develop color (this is especi- ally true of the iodides), due to decomposition, and are generally kept in amber-colored bottles. General Methods of Preparation.-By the action of a halogen acid on an alcohol. (An alcohol contains the-OH group. Exam- ples of alcohols are C2H,50H, ethyl alcohol, CaH70H, propyl alcohol, and in general ROH.) CH5 OH + II Br -->C2IIsBr + 1O20 Ethyl alcohol Or, more generally, R OH + IH X RX + HO20 (Whenever throughout the text " R " is used in an equation, it implies that the reaction is a general one; or, in other words, is a " type " reaction. This does not necessarily imply that where specific examples are given, they cannot illustrate general type reactions. As a matter of fact, in most cases the specific examples do illustrate type reactions.) HALOGEN DERIVATIVES This reaction is analogous to the " neutralization " reaction in inorganic chemistry, such as Na I OH + HI Cl -- NaCI + H20. However, the production of NaC1 is an instantaneous reaction, whereas the formation of RX is a comparatively slow process; and in the production of RX we must have a dehydrating agent present to remove the water as fast as it is formed, otherwise the reaction is reversible. Another method is the action of a phosphorus halogen com- pound on an alcohol; e.g., CaH7OH + PC15 -- C3H7Cl + POCl3 + HCI Propyl alcohol Propyl chloride 3C3H701H + PBr3 - 3C3H7Br + H3PO3 Phosphorus acid or ROH + PC15 -* RCl + POCl3 + HCI 3ROH + PX3 -- 3RX + P(OH)3 A third method consists in the addition of halogen acids to unsaturated compounds; e.g., HH HH C=C + HBr --*H-C-C-Br HH HH or C,H2. + HX -- C,H2.+1X or RX Properties.-The halogen compounds react with many reagents to form diverse products. The following are examples of a number of type reactions: 2C2H5I + 2Na -- C2H5-C2H5 + 2NaI Butane (The Wurtz Synthesis.) C2H5 C2H5I + Mg -~ Mgi Magnesium ethyl iodide (I) METHYL CHLORIDE Compounds of type (I) are known as Grignard's general type formula being R -Mg. X. reagent, the C2H5I + KCN C2H5I + KOH C2H51 + AgN02 - C2HsCN + KI Ethyl cyanide -- C2H5OH + KI Ethyl alcohol -- C2H5N02 + AgI Nitroethane C2H5I + NaOC2H5 -- CHC2H50C2H5 + NaI Sodium ethylate Ethyl ether CsHsI + NH3 C2H5I + HOH H -* C2H5N H \H I Ethyl ammonium iodide -- C2H5OH + HI C2HsI + alc. KOH -- C2H4 + KI + H20 (At this stage the student is not expected to memorize these equations, but rather, by examining them, to understand why the halides find such extensive applications.) (Many of the reactions illustrated are of the " double decom- position " type.) Methyl chloride, CH3C1, and Ethyl chloride, C2H5C1, are used as local anesthetics, for when sprayed upon the skin the liquids evaporate rapidly, thereby cooling the tissue. To some extent they are used for refrigerating purposes. Ethyl bromide, C2H5Br, has also been used as an anesthetic. CH3 - CH2. CH2I n-Propyl iodide CH3 - CHI. CH3 Isopropyl iodide Dihalogen Derivatives of the Paraffins.-These have the general formula CnH2nX2 (C2H4Br2, dibromoethane, and C3H6C12, dichlo- ropropane, are examples). They are usually prepared by the addition of a halogen to an unsaturated hydrocarbon: C2H4 + Br2 - C2H4Br2 Ethylene bromide HALOGEN DERIVATIVES (CH212 is of interest since it is the heaviest organic liquid, its specific gravity being 3.292 at 180.) Trihalogen Derivatives of the Paraffins.-The important com- pounds of this type are chloroform, CHCl3, bromoform, CHBr3, and iodoform, CHI3. Chloroform, CHC13, is prepared by the action of chlorine (in the form of bleaching powder) on (1) ethyl alcohol or (2) acetone. H H + Cl C1 (1) H-C-C-OH H H CH3 - C-0 H H (A) O - CH3. C' H (Acetaldehyde) Cl + 3C12 --> Cl-C - |- H Cl (Trichloroacetaldehyde or "chloral") Ca(OH)2 > CHCl3 + (HCOO)2Ca (Calcium formate) (A) represents a hypothetical compound, or at least one which has not so far been isolated. Its instability, it would seem, is due to the Cl and OH groups being attached to the same carbon atom. The type formula for an aldehyde is R -CH discuss these aldehydes later, p. 67. We shall Cl (2) CH3 CO CH3 + 3C12 -. Cl-C- CO CH3 + NaO H (Acetone) C1 (Trichloroacetone) -> CHCl3 + CH3COONa (Sodium acetate) CH3. C // \H CHLOROFORM Acetone is the simplest of the group of compounds known as " ketones." Their type formula is R CO - R (p. 67). In practice the necessary chlorine is obtained by the use of bleaching powder. Chloroform is now made on a large scale by the reduction of CC14: CC14 + H2 -4 CHC13 + HC1 Chloroform (trichloromethane) is a colorless liquid with a sweet taste and suffocating odor. Its b.p. is 610. It is slightly soluble in water. It is non-flammable. Its anesthetic properties were discovered by Dr. Simpson of Edinburgh, in 1848. Chlofororm has a tendency to decompose when exposed to air and light: CHC13 + 0 -- COC12 + HC1 (Phosgene) 2CHC13 + 30 -- 2COC12 ± C12 + H20 To prevent this, ethyl alcohol (to the extent of about 1 per cent) is added to it. Pure CHC13 does not react with silver nitrate, but, if any decom- position has occurred, a precipitate of AgC1 forms. (CHC3 alone is now rarely used as an anesthetic, for ether has largely taken its place. Sometimes a mixture of ether and chloro- form is used. The advantage of ether over chloroform is that it is less dangerous and the after-effects are not so pronounced.) Acetone and chloroform combine to form chloretone, (CH3)2.C(OH) - CC13, used extensively as a hypnotic, anodyne and preservative. Chloroform combines with concentrated nitric acid to form chloropicrin, or nitrochloroform, a substance that was used in the late war as a lachrymator ("tear gas"): CHCl3 + HN03 --- CC13NO2 + 1120 When prepared on a large scale, the chloropicrin is made by the action of bleaching powder on picric acid (p. 263). Chloroform is sometimes used as a " preservative " for the prevention of bacterial growth, though for most purposes toluene has largely taken its place. Chloroform is an excellent solvent for many organic compounds. It dissolves fats, rubber, etc. HALOGEN DERIVATIVES Bromoform, CHBr3, is prepared in a manner quite analogous to chloroform. Its anesthetic properties are less marked. Iodoform (triiodomethane), CHI3, is prepared by adding iodine to a warm solution of sodium carbonate containing alcohol or acetone-in principle analogous to the preparation of chloroform. The odor of iodoform is not only characteristic, but powerfdl, hence the reaction is used as a test for either alcohol or acetone. Iodoform is a powerful antiseptic and disinfectant. (The anti- septic properties are due to its gradual decomposition with the liberation of iodine.) Tetrahalogen Derivatives of the Paraffins, CF4, CC14, CBr4 and CI4. Of these, only the second, carbon tetrachloride, is important. It is made commercially by passing chlorine into carbon disulfide, using iron, iodine or antimony pentasulfide as a catalyst: CS2 + 3C12 -- CC4 + S2C12 (We have already mentioned the production of CC14 from methane by the action of chlorine: CH4 + 4C12 -- CC14 + 4HC1.) Carbon tetrachloride is a colorless liquid with an ethereal odor. It is a good solvent for gums and resins and is also a constituent of many cleaning solutions. It is an anesthetic, but is not used because of its bad effect on the heart. It is used in fire extin- guishers (" Pyrene "). Its vapor produces severe headaches. (During the past few years a number of chlorinated paraffins, used as solvents, have been prepared on a commercial scale. One such is tetrachloroethane, made by the action of chlorine on acetylene: C2H2 + 2C12 -- C2H2C14.) Halogen Derivatives of Unsaturated Hydrocarbons.-The names and structures of a few of these will be given: Cl Cl Cl Cl I I I H-C=C-H C-C=C--C1l Dichloroethylene Tetrachloroethylene HALOGEN DERIVATIVES OF UNSATURATED HYDROCARBONS 47 (These are used as solvents.) CH2==CHBr Monobromoethylene 1 2 3 CHBr--CHCH3 1-Bromopropylene CH2=CHI Monoiodoethylene CH2=CBrCH3 2-Bromopropylene CH2=--CH - CH2Br 3-Bromopropylene (allyl bromide) (CH2=CH- CH2 is known as the allyl group.) Br H C=C Bromoacetylene I I C-C Diiodoacetylene READING REFERENCE CLARK-Applied Pharmacology. (1923), chap. 9 (Anesthetics). CHAPTER V ALCOHOLS METHANOL, which is methyl (or wood) alcohol, and ethyl (or grain) alcohol, are the two most important substances belonging to this group. The alcohols may be considered as hydrocarbons in which one or more of the hydrogens are replaced by OH groups. (They may also be regarded as derived from water in which one of the hydro- gens. is replaced by R; H-OH -- R-OH.) The relationship of the hydrocarbons to the alcohols is shown here: CH3H (methane) - CH30H (methano' or methyl alcohol) C2H5H (ethane) - C2HsOH (ethyl alcohol) C3H7H (propane) - C3H7OH (propyl alcohol) etc. ctc. etc. RH . (alkane) - ROH (alkyl alcohol) Nomenclature of Alcohols.-There are a number of systems employed. (1) The ending e of the hydrocarbon containing the same number of carbon atoms is changed to the eriding ol: C2H6, ethane -- C2HsOH, ethanol C3H6, propene - C3H,OH, propenol (2) The alcohol is named according to the alkyl group it con- tains: C2H5H, ethane - C2H5, ethyl group -- C2H5OH, ethyl alcohol, or ethyl hydroxide. NOMENCLATURE OF ALCOHOLS (3) The alcohols are looked upon as " carbinol" derivatives: H H-C-OH is " carbinol " H CH3 CH2 OH, methyl carbinol CH3 CHa> CH. OH, ethyl methyl carbinol (Methyl carbinol is carbinol in which one of the hydrogen atoms is replaced by CH3, and ethyl methyl carbinol is carbinol in which one hydrogen atom is replaced by C2H5 and another by CH3.) Alcohols may contain more than one OH group provided they are attached to different carbon atoms; e.g. H H H H H I I I I I H-C-C-H H-C-C-C-H I I I i I ' OH OH OH OH OH 1, 2-Ethanediol 1, 2, 3-Propanetriol or or 1, 2-dihydroxyethane 1, 2, 3-trihydroxypropane or or glycol glycerol etc. We shall see in a later chapter that the sugars contain several OH groups. (Two or more OH groups attached to the same carbon atom give rise, as a rule, to unstable compounds: /H R-C----OFH - R-C=O SOH H (an aldehyde) the unstable dihydroxy compound being converted into an alde- hyde. We shall explain the oxidation of an alcohol to an aldehyde in this manner.) AN INTRODUCTION TO ORGANIC CHEMISTRY BY ALEXANDER LOWY, PH.D. Professor of Organic Chemistry, University of Pittsburgh AND BENJAMIN HARROW, PH.D. Associate in Physiological Chemistry, College of Physicians and Surgeons, Columbia University NEW YORK JOHN WILEY & SONS, INC. LONDON: CHAPMAN & HALL, LIMITED 1924 ALCOHOLS An alcohol with one OH group is monatomic, with two OH groups, diatomic, with three, triatomic, etc. If we take an alcohol, such as ethyl alcohol, C2H60, and treat it with sodium, only one atom of hydrogen (out of the six present) is liberated: C2H60 + Na -- C2HsONa + H This particular atom of hydrogen obviously differs in some way from the other five atoms. The possibility that this difference is due to a difference in position within the molecule is borne out by the fact that when we treat the alcohol with, say, hydrogen iodide, one atom of iodine replaces one atom of hydrogen and one atom of oxygen,-one iodine, in other words, replaces one hydroxyl group: C2H1150H + HI - C2HsI + HOH It would seem, therefore, as if one hydrogen in ethyl alcohol is attached, not to the carbon atoms (like the other five hydrogen atoms), but to the oxygen atom: H H I I H-C-C-O-H H H and all the reactions of the many alcohols known (some of which will be discussed presently) strengthen this view. Types of Alcohols. H 1. The presence of the group -C-OH indicates a primary H alcohol: e.g., CH3-C OH. H TYPES OF ALCOHOLS 2. The group CH3 CH3-C-OH H 3. The group CH3 CH3-C--OH C2H5 -C-OH indicates a secondary alcohol: e.g., H Isopropyl alcohol or dimethyl carbinol -C--OH indicates a tertiary alcohol: e.g., Dimethyl ethyl carbinol These three types of alcohols yield various oxidation prod- ucts. When a primary alcohol is oxidized, we first get an aldehyde; e.g., H H H H I 0o* I H-C-C-OH ---- H-C-C--O H - H-C-C=O + H20 H H H OH H H Ethyl alcohol (A) Acetaldehyde (It is believed that (A) is an intermediate compound, though it has not, as yet, been isolated. It has already been pointed out that a compound containing two OH groups attached to the same carbon atom is usually unstable, water splitting off in the manner shown.) The aldehyde on further oxidation yields the corresponding acid: H O CH3-C --S CH3-C \H OH Acetaldehyde Acetic acid * 0 refers to oxidation. ALCOHOLS (Let us remind the student at this point that the group -C H is characteristic of aldehydes, and the group -C / is charac- OH teristic of organic acids.) We see then that the oxidation of a primary alcohol yields first an aldehyde and then an acid containing the same number of carbon atoms as the original alcohol. When a secondary alcohol is oxidized we get a ketone; e.g., CH3 CH3 CH3 CH3--C-OH --- CH3-C-O H ---- CH-3-C=O H oH Isopropyl alcohol (not isolated) Acetone or 2-propanol R C= represents ketones, and acetone is the simplest member of the series. On further oxidation we get acids con- taining less carbon atoms than the original ketone or alcohol. (There are two isomeric propyl alcohols, the normal, /H CH3. CH2- CH20H, and the iso, CH3-C-OH. The latter, CH3 being a secondary alcohol, yields a ketone-acetone--on oxidation; the normal, being a primary alcohol, yields first an aldehyde- propionaldehyde-and then an acid-propionic acid.) When a tertiary alcohol is oxidized, a mixture of acids and ketones are obtained, each substance formed having less carbon atoms in its molecule than the original tertiary compound: e.g., CH3 I 0 CH3-C-OH > H. COOH (Formic acid) I CH3 COOH (Acetic acid) CH3 CH3. CO CH3 (Acetone) Trimethyl carbinol or CO2 + H20 Tertiary butyl alcohol METHODS OF PREPARATION We therefore see that on oxidation primary alcohol -- aldehyde -, acid secondary alcohol -- ketone -> decomposition products tertiary alcohol -- decomposition products Methods of Preparation.-Alcohols are produced in the course of destructive distillation (p. 57) and fermentation (p. 58). Other methods are the following: The action of moist silver oxide or aqueous NaOH or KOH solution on an alkyl halogen compound, as C2H5 I -+ Ag[ OH * C2H50H + AgI or CH3 [Br + K OH -- CHaOH + KBr The reduction of aldehydes (yielding primary alcohols); as 0 CH3.C H + H2 - CH3 CH20H Acetaldehyde (The student will recall that the oxidation of a primary alcohol yields an aldehyde; we may therefore expect that the reduction of the aldehyde will yield the alcohol. The reducing agent may be sodium amalgam and water, or hydrogen in the presence of nickel.) The reduction of ketones (yielding secondary alcohols); as CH3 + H2 CH3 CH3C O ---- CCHH Acetone Isopropyl alcohol The action of nitrous acid on a primary amine (that is, a sub- stance formed when one of the hydrogens in NH3 is replaced byR, giving R NH2; (see p. 132); as C2H5NH2 + HONO -- C2HsOH + N2 + H20 Ethyl amine Nitrous acid ALCOHOLS The hydrolysis of esters; as CH3 COOC2H5 + HOH -> CH3COOH + C2H5OH Ethyl acetate In presence of acids Acetic acid or bases (An ester is an acid in which the ionizable hydrogen is replaced by an alkyl group: R COOH -- R. COOR.) (Acid) (Ester) Various secondary and tertiary alcohols can be prepared by means of the Grignard reaction; e.g., + R-Mg-X --+ Alkyl magnesium halide R 1 /OMgX+HOH /R R-C -- R-C-OH HAddition compound Secondary alcohol Addition compound Secondary alcohol Illustration: C2H5 C2H5 0 I H20 I CH3. CZH + C2H5 Mg. I -- CH3 . C--OMgI --- CH3-C-OH Acetaldehyde Ethyl magnesium iodide H H OMgX+H O] R-Mg-X -> R-C 2C2HO50H + 2C02 The best temperature for this fermentation ranges from 25-300. (Small quantities of impurities, such as glycerol, succinic acid, butyl alcohol, isoamyl alcohol, etc., are also found.) The alcohol in the " wort " (which is the name given to the liquor formed in the course of the fermentation process and which contains about 14 per cent of alcohol), is purified by fractional distillation. Com- mercial ethyl alcohol contains about 95 per cent of alcohol. A still higher percentage of alcohol (" absolute," or nearly 100 per cent alcohol) may be obtained by the addition of calcium oxide (quick- lime) or anhydrous copper sulfate (which are dehydrating agents) 1 A dye intermediate is an organic compound used in the manufacture of dyestuffs. 7RALI .ITY FMIAL W4TORY CrSo DIU4 rOR NITROCCU NEUS PURPL Me -r-Akr (/7, Full scan of this foldout is at the end of this text PERCENTAGE OF ALCOHOL IN BEVERAGES to the liquid and allowing it to stand a day or two; it is then dis- tilled. (Such substances as grape juice, corn syrup and molasses are already rich in glucose. Here the preliminary diastase treatment, consisting in the conversion of starch into glucose, is unnecessary.) Properties and Uses.-Ethyl alcohol is a colorless liquid, has a characteristic odor and a sharp burning taste. (b.p. 78.4'.) In the form of tinctures (alcoholic solutions or extracts of medicinal substances) it is extensively used in medicine. In certain diseases, such as pneumonia, it has proved a valuable therapeutic agent. The use of alcohol in the industries is very extensive. As a preservative, as an antiseptic, in the preparation of denatured alcohol and various drugs and medicinals, as a solvent, in per- fumery, as an essential constituent necessary for the manufacture of iodoform, chloroform and ether, alcohol is in constant demand. (Additional uses will be found in the chart facing p. 59.) Denatured Alcohol.-This is alcohol which has been made unfit for drinking purposes and external applications, but which can still be used in the industries. Some of the substances used in " denaturing " are methanol, benzine, pyridine, ether, acetone- substances with disagreeable odors and flavors, and possessing poisonous properties. No less than forty-five different formulas have been granted in the United States for the preparation of denatured alcohol for various industrial uses. Denatured alcohol is tax-free. Medicated Alcohol is alcohol unfit for drinking purposes, but suitable for external applications. Some of the substances used in the preparation of medicated alcohol are tartar emetic, formalde- hyde, phenol, diethyl phthalate, benzene, acetone, zinc phenolsul- fonate, etc. Percentages of Alcohol in Beverages.-Beer= 2-5 per cent; wine= 7-11 per cent; fortified wine=17-20 per cent; whiskey, brandy, gin, rum, etc. = 40-75 per cent. The percentage of alcohol in a number of pharmaceutical prep- arations is relatively high. Aromatic spirits of ammonia= 68 per cent; spirits of camphor= 90 per cent; tincture of iodine= 83 per cent, etc. For further details consult U. S. Pharmacopeia IX. (When?ve, fermented liquors are distilled, not only do we get ethyl alcohol, but also small quantities of esters and a ALCOHOLS number of the higher alcohols, the mixture of these being sub- stances known as fusel oil. Some claim that the presence of fusel oil in liquors is far more harmful than the ethyl alcohol itself. In this connection the following information may be of interest. We know that the principle constituent of fusel oil is isoamyl CH3 alcohol, CH3CH.CH2. CH2H, and we know that the source of this is isoleucine, an amino acid obtained from the protein present in cereal or potato (see the chapter on proteins, p. 137. The bacteria present convert the isoleucine into isoamyl alcohol. It has, however, been shown that this conversion-and hence the production of isoamyl alcohol-may be prevented by the addition of ammonium salts, which the bacteria prefer.) CH3 H Isopropyl alcohol, CCH , is used under the name of CH3' OH " petrohol " as motor fuel and solvent. (Normal butyl alcohol is obtained as a by-product in the fermentation of sugar and is used to a large extent as an organic solvent.) Isoamyl alcohol is converted to isoamyl acetate and thus used in the manufac- ture of varnishes and fruit essences. Cetyl alcohol forms (as palmitic ester) the chief constituent of spermaceti (a wax-like substance found in the head of the sperm whale), while myricyl alcohol is present as palmitic ester in beeswax and in Carnauba wax. The alcohols are prepared from all these esters by hydrolysis with boiling alcoholic KOH solution. Diatomic Alcohols.-The simplest of these is dihydroxy- ethane, known as glycol, CH20H. It may be prepared by the CH20H action of silver hydroxide on the corresponding dibromo com- pound: CH2 Br Ag OH CH20H + - I + 2AgBr CH2 I Br Ag OH CH20H but commercially it is made from ethylene: HOCI CH2-Cl Hydrolysis CH20H CH2=CH2 - I I CH2-OH CH2OH Ethylene chlorohydrin TRIATOMIC ALCOHOLS Glycol is used as a solvent and preservative. The general chemical properties resemble the alcohols, except that we here deal with two OH groups instead of one OH group. Triatomic Alcohols.-The best known of this group is glycerol (also called glycerine), CH20H (or 1, 2, 3-propantriol), which is CHOH CH20H produced as a by-product in the manufacture of soap (p. 92). C3H5(OOC - C17H35)3+3NaOH -- 3C17H35- COONa+C3H5(OH)3 (A typical compound in a fat) (A typical compound in a soap) (Glycerol) (Details of this process will be given in the chapter on esters, p. 93.) Properties and Uses.-Glycerol is a colorless, odorless syrupy liquid, having a sweetish taste. It is miscible with water and alcohol and is a good solvent and a dehydrating agent. It is used in medicine; as a sweetening agent; as a preservative for tobacco; in perfumery; in cosmetics; in ink for rubber stamps, etc. When glycerine is heated alone or in the presence of a dehy- drating agent, acrolein is produced: CH20H CH2 I -2H20 II CHOH - CH CH20H CHO (The odor of burnt fat is due to the production of acrolein.) As may be seen from its formula, gylcerol is both a primary and a secondary alcohol, and may, therefore, be expected to show the properties of both types of alcohols. When oxidized, aldehydes, acids and ketones are formed. Treatment with acids gives esters. One of the compounds obtained when nitric acid and glycerol react is of importance; and that is the glyceryl trinitrate or, as it is commonly called, nitroglycerine. CH20H HONO2 CH2-ONO2 CHOH + HONO2 -- CH-ON02 + 3H20 CH20H HONO2 CH2-ONO ALCOHOLS (Cone. sulfuric acid is added to remove the water that is formed.) The nitroglycerine is a dangerous explosive to handle, but when mixed with an inert substance, like infusorial earth, " kieselguhr," thereby becoming dynamite, it can be handled with much less risk, though none of its explosive properties are lost. (Starch and sawdust are now used in the place of " kieselguhr," and oxidiz- ing agents such as ammonium or potassium nitrate are added to aid combustion.) We owe the invention of dynamite to Alfred Nobel, a Swedish engineer, who accumulated a fortune as a reuslt of his invention and who bequeathed it to the Swedish Academy for the purpose of founding the Nobel Prizes. (Vapors of nitroglycerine produce severe headache. In medi- cine, a 1 per cent solution in alcohol is used. It has a powerful action on the arteries and is used as a heart stimulant.) (Glycerol is formed in the digestive tract when the fat in food is hydrolyzed by the enzyme " lipase " of the pancreatic juice. It is also. believed that glycerol plays an important part in the oxi- dation of fats and carbohydrates in the body, for it would seem that one of the intermediate substances formed in such oxidations is glycerol, or a substance very closely allied to it.) Polyatomic Alcohols.-The careful oxidation of the penta- and particularly the hexa-hydroxy alcohols, leads to the com- pounds known as sugars; but these we shall discuss later. In the meantime, we shall merely mention the names of a few polyatomic alcohols, and write their formulas: CH20H CH20H CH20H CHOH CHOH IHOH CHOH CHOH CHOH I I I CH20H CHOH CHOH Erythritol CH20H CHOH Arabitol CH20H Mannitol Erythritol occurs in nature, either in the free or combined state, in algae and certain lichens. A source of arabitol is gum POLYATOMIC ALCOHOLS arabic. The source of mannitol is the manna ash tree, which, however, is not believed to be related to the " manna " of the Bible. Dulcitol and sorbitol are isomers of mannitol. UNSATURATED ALCOHOLS CH2==CHOH, ethenol. CH2=:CH - CH2OH, allyl alcohol, or A3-1-propenol is present in pyroligneous acid. (Remember that "A " indicates a " double bond," and that " A3 " indicates double bond in position 3. The ending " ol " in propenol indicates an alcohol, and the "1 " before the name means that the OH group is in position 1.) These compounds possess the general characteristics of alcohols, and being unsaturated compounds, they form additive products with hydrogen, with halogens, with halogen acids, etc. READING REFERENCES SADTLER--Chemistry of Familiar Things. (1915), chap. 16 (Fermenta- tion). DUNCAN-The Chemistry of Commerce. (1907), chap. 7 (Industrial Alcohol). HARDEN-Alcoholic Fermentation. HAWLEY-Wood Distillation. RoGERs-Manual of Industrial Chemistry. (1921), pp. 634-652 (The Destructive Distillation of Wood); pp. 739-752 (Glycerine). CHAPTER VI ETHERS ETHERS may be considered as derived from alcohols in which the H of the ROH is replaced by an R group; or they may be looked upon as derived from HOH in which both hydrogens are replaced by R groups. The ethers are really organic oxides. (HOH = H20 = water= hydrogen oxide; and R-O-R= R20. For example, C2H5-O-C2H5= (C2H5)20= ethyl oxide, com- monly known as " ether.") Types of Ethers.-If the two R's represent the same groups, then we get a simple ether. CH3 -O-CH3, methyl ether C2H5-O-C2H5, ethyl ether If the two R's represent different groups, we get a mixed ether. CH3-O-C2H5, ethyl methyl ether C2H5-O-C3H7, ethyl propyl ether General Methods of Preparation.-The action of an alkyl halide on the sodium alcoholate; e.g., C2Hs01Na + I C3H7 -- C2H5O C3H7 + NalI Sodium ethylate propyl iodide Ethyl propyl ether (This method, the Williamson's synthesis, enables one to pre- pare either a simple or a mixed ether.) Heating a mixture of silver oxide and alkyl halide; e.g., 2C2H5I + Ag20 --+ (C2H5)20 + 2AgI Ethyl oxide or ethyl ether or ether (This reaction proves that ether is an oxide.) ETHER General Properties.-The ethers are colorless, neutral liquids, more volatile than the corresponding alcohols and lighter than water. They are very stable and inactive, and are therefore used as solvents. The ethers, especially the lower members, are highly flammable. Sodium, ammonia, alkalis and dilute acids have no action on them. Hydriodic acid acts in one of two ways: ROR + HI - ROH + RI ROR + 2HI ~ 2RI + H20 (When heated) Phosphorus pentachloride has no action in the cold, but when heated, ROR + PC15 -> 2RCl + POC13 Steam at 1500 decomposes them: ROR + H20 --> 2ROH Chlorine replaces the hydrogens in the alkyl groups. Ether, C2H5-O-C2H5 (also known as ethyl ether, sulfuric ether and ethyl oxide) is the most important substance of this group. Ether is manufactured by the " continuous etherification proc- ess." Equimolecular proportions of alcohol and sulfuric acid are mixed: C2H5 OH + H2 - C2H50 H HO/ Ehtyl hydrogen sulfate or ethyl sulfuric acid The mixture is now heated to 130-140' and more alcohol added: O0 C2H5 02OH + HI OC2H5 - (C2H5)20 + H2SO4 OH (The sulfuric acid is regenerated and used over again until the acid becomes too weak to react with the alcohol.) PREFACE IN the preparation of this work the authors have tried to keep a number of objects steadily in mind. In the first place, they desired to embody in the work material which could be satis- factorily treated in a course in which the theory of organic chem- istry is covered in two semesters (two hours a week). They were also anxious that such material should include not only the well-recognized basic principles of organic chemistry, but also its more recent and more important applications; the entire story being woven together into a simple and readable narrative. The authors have also kept in mind the many connecting links that bind organic chemistry to a number of other sciences,- to medicine, dentistry, pharmacy; to agriculture; to the bio- logical sciences; hence, the inclusion of such chapters as those dealing with lipoids; nucleoproteins and their decomposition products; the chemical changes which foodstuffs undergo in the body; plant and animal pigments; enzymes, vitamins and hor- mones; organic compounds of arsenic and other metals; dyes and stains, etc. The text can, therefore, be appropriately used not only by the student who is taking organic chemistry as part of a general academic course, or as preparation for a more extended course in chemistry, but by one who is preparing for the medical, dental, pharmaceutical or other biological sciences. The book is not intended to act as a guide for laboratory manipulations; details for the preparation of compounds are, therefore, intentionally omitted. Neither, with a few exceptions, are boiling points, melting points or other physical constants included in the body of the work; some of these will be found in the form of a table in the appendix. To aid the student in naming organic compounds, a brief chapter (XXXVII) is devoted to this topic. The structure of benzene and its derivatives is shown in v ETHERS The equation may be expressed: H2S04 C2H5 IOH + HI OC2H5 --- C2H5-O-C2H5 + H20 Properties.-Ether is a colorless, volatile liquid, with a very characteristic odor. b.p. 34.60. Specific Gravity=.736 at 00. It is highly flammable, burning with a luminous flame, and is explosive when mixed with air and ignited. It is slightly soluble in water and is used for extracting certain substances from an aqueous solution. As a solvent for fats, oils, resins, alkaloids, etc., ether is unsurpassed. It can be used as a solvent for quite a number of organic substances. It also dissolves iodine, bromine, sulfur, phosphorus, ferric chloride, etc. It is used with alcohol in the manufacture of guncotton. Due to its rapid evaporation, it can be used for- refrigerating purposes. As an anesthetic, it was introduced in surgery by Dr. Morton, a Boston dentist, in 1846. As an anesthetic, ether is preferred to chloroform, for the physio- logical effects can be better controlled. Ether for this purpose must be highly purified. (Ether, chloroform and other anesthetics are, chemically, more or less inert substances and are more soluble in lipoids-typical cell constituents-and lipoid solvents than in water.) Other Ethers. CH2OC2H5 CH2=CH. CH2\ CH20C2H5 CH2==CH CH2/ Glycol ether Allyl ether READING REFERENCE BASKERVILLE-The Chemistry of Anesthetics. Science, 34, 161 (1911). CHAPTER VII ALDEHYDES AND KETONES AN aldehyde, R CHO, may be regarded as a hydrocarbon wherein a hydrogen atom has been replaced by the - CHO group. 0 The type formula for an aldehyde is R-C , and for a ketone, H R >IC=0; so that a ketone may be regarded as an aldehyde in which the H of the CHO group is replaced by R; and, on the other hand, an aldehyde may be regarded as a ketone in which one of the R groups is replaced by H. Both have the >C=O or carbonyl grouping, have a number of common properties and they are, therefore, considered in the same chapter. (In the chapter on sugars, the student will discover that most of the sugars contain either aldehyde or ketone groupings, and that a number of their properties depend upon these groups; so that much that is gleaned from this chapter can be applied later.) Nomenclature of Aldehydes.-(1) Change the e ending of the hydrocarbon having the same number of carbon atoms (or the ol ending of the alcohol) to al. C2H6, ethane C2H5OH, ethanol - CH3. CHO, ethanal (2) The aldehydes may also be named after the corresponding acids formed when the aldehydes are oxidized. H. COOH, formic acid H -CHO, formic aldehyde or formaldehyde CH3 . COOH, acetic acid - CH3 CHO, acetic aldehyde or acetaldehyde ALDEHYDES AND KETONES C2H5. COOH, propionic acid - C2H5 -CHO, propionic aldehyde or propionaldehyde C3H7 COOH, butyric acid - C3H -CHO, butyric aldehyde or butyraldehyde etc. (Never write the group - C-OH to represent the aldehyde grouping, but always CHO. Remember that OH stands for alcohol and in alcohols the linking is R-0-H and in alde- hydes, R-C=0.) \H When an aldehyde is treated with phosphorus pentachloride, the reaction is quite different from that obtained when PC15 acts on an alcohol. Taking acetaldehyde as an example, C2H40+ PCl5 -> C2H4C12 + POCl3 Dichloroethane An examination of the dichloroethane reveals that it is the unsymmetrical variety, the two chlorine atoms being attached to the same carbon atom: H H H-C-C--Cl H C1 which suggests that the oxygen atom in aldehyde occupies a posi- tion in the chain corresponding to these two chlorine atoms; that is, H H I I H-C- or CH3 C==O H \H Nomenclature . of Ketones, R. CO R.-(1) Change the e ending of the hydrocarbon with the same number of carbon atoms to one: C3H, propane -- CH. CO. CH3, propanone C4H1 o, butane - CH3- CH2- CO. CH3, butanone C5H12, pentane - CH3 CO. CH2- CH2. CH3, 2-pentanone CH3CH2COCH2 - CH3, 3-pentanone etc. PREPARATION OF ALDEHYDES AND KETONES (The type structure for ketone, R CO. R, indicates that even the simplest ketone must contain at least three carbon atoms.) (2) Name the compound in accordance with the type of group rep- resented by R, remembering that > C=O is the ketonic grouping: CH3 -CO-CH3, dimethylketone C2H5-CO-CH3, ethyl methyl ketone C2H5-CO-C9H19, ethyl nonyl ketone etc. As with ethers, so with ketones: there are simple and mixed ketones. When R=R' we have a simple ketone; when R is different from R', we have a mixed ketone; so that C2H5. CO C2H5 is a simple ketone, and C2H5. CO. C4H9 is a mixed ketone. Preparation of Aldehydes and Ketones.-The oxidation of a primary alcohol yields an aldehyde; e.g., H I (K2Cr207+H2SO4) 7IH CH3-C-OH + 0 > CH3-CO I H Ethyl alcohol - ICH3-C 0 + HO20 Acetaldehyde The oxidation of a secondary alcohol yields a ketone; e.g., /CHa CH3 CH3--CH + 0 - CH3-C 0 H \OH OH Isopropyl alcohol -* CH3-C-CH3 + H20 Acetone Hydrolysis of dihalogenated hydrocarbons; e.g., H H O CH3-C- Cl ± H OH CH3- COH --* CH-Ct >0d H OH Ethylidene chloride ALDEHYDES AND KETONES (CH2C1-CH2C1 is ethylene chloride, but CH3 -CHC12 is ethyl- idene chloride.) cl HIOH H CH- C-CH3 + -- CHI-C- -----CH-- C-CH S\ I1 Ici HIOH CH3 O 2, 2-Dichloropropane Aldehydes may be obtained by heating the calcium salts of certain organic acids with calcium formate; e.g., CH3- COOca 1 + - CH3CHO + CaC03 H-CO Oca When the calcium salts alone are heated we get ketones; e.g., CH3 OO Ca > CH3COCH3 + CaCO3 CH3CO 0 or CH3 COOca H CH-CO'CAH+CaCO3 C2 HCO Oca Chemical Properties of Aldehydes and Ketones.-We have already mentioned the fact that since both aldehydes and ketones contain the carbonyl, C=0O group, they have many properties in common. The )C-O group may be looked upon as an unsaturated group, for it contains a double bond; which means that certain types of addition compounds are possible. Acetaldehyde (CH3. CHO) and acetone (CH3. CO. CH3) are here taken as typical examples of aldehydes and ketones respect- ively. CH3"COO, 'The true formula for calcium acetate is CCOa, but for the sake CH3-COO/ of convenience we have halved it, and write the symbol for calcium in small letters: ca= Ca. Ketones, e.g., CH3 CO CH3 H H-C-C- OH Acetic acid -- Decomposition of molecule producing acids with lower carbon content as H-COOH and CH3-COOH and C02+H2O CH3 CH, CH3--C-OH I/H I - + CH3-C-OH CH3 CH3 A secondary A pinacol alcohol (tetramethyl glycol) H H H H A primary alcohol H H I I -* H--C(-OH H OSO2Na Acetaldehyde sodium hydrogen sulfite H - CH3-C-OH NH2 Acetaldehyde ammonia OH CH_ --CH3 OSO2Na Acetone sodium hydrogen sulfite Complex condensation products, in place of an addition compound, are formed Oxidation Reduction NaHSO3 Sodium bisulfite NH3 Reagents Used Aldehydes, e.g. CH3 -CHO H -, CH3-C-OH CN Acetaldehyde hydrogen cyanide or ethylidene cyanohydrin /H CH3---C 1 \CI Ethylidene chloride -t substitute in CH3 group: e.g., C1 OH - CH3-C--CH3 CN Acetone hydrogen cyanide C1. -sCH3--4CH3' 2, 2-Dichloropropane --+ substitute in CH3 groups: e.g., CCI.CO CH3 Trichloroacetone Trichloroacetaldehyde H H OH3*O~ ±HN*OH -* CH3.O==NOH* Acetaldoxime H OH3CO~ +H N-NH2 - CH,-C=NNH2 Acetaldehyde hydrazone CH3 CH3 C=O±HNOH - C=NOH CH3 CH3 Acetketoxime CH3 CH3 O= 0±H- NNH, -- +=NNH2 CH3 OH3 Acetone hydrazone * The = NOH group is known as the " oxime" group. HCN PCI Halogens C]-C-C C1 H2N-OH Hydroxylamine H2N-NH2 Hydrazine or aminoamine Reagents Used H2N-NHC6sH5 Phenylhydrazine C2H5OH (In presence of a de- hydrating agent, such as HC gas) Aldehydes, e.g., CH3 CHO Z H CHC H N-NHC6H5 - CH3 -C=N -NHC6H5 Acetaldehyde phenylhydrazone /H F OC2H5 CH3-C O+H OC2H,5 /H -- CH3-C-OC2H5 \OC,He Acetal Ketones, e.g., CH3. CO - CH CH3 C=O+ N.NHC6H5 CH3 No similar reaction CH3 -* C-=N.NHC6H5 CHd Acetone pheny!hydrazone Aldehydes reduce ammoniacal silver nitrate solution to Ketones do not produce silver mirror T Phenylhydrazine is hydrazine wherein one hydrogen has been replaced by the monovalent CeHs (phenyl) group (p. 203). The phenyl group bears the same relationship to benzene, CsH, that the methyl group does to methane. ALDEHYDES AND KETONES ALDEHYDES Formaldehyde, H. CHO (also known as methanal) is manufac- tured by passing methanol vapor and air over copper gauze: CH30H + 0 -- HCHO + H20 The reaction is exothermic and the copper need not be heated ex- cept to start the reaction. It is a gas with irritating odor, soluble in water. The formalin of commerce is a 35-40 per cent aqueous solu- tion of the gas. A small amount of methanol must be present in the formalintoprevent the polymerization of the formaldehyde. For dis- infecting purposes, specially constructed lamps are used containing methanol, which when burnt (in the presence of copper or platinum) yields formaldehyde. It is used as a food preservative, disinfectant and germicide, both in the form of gas and in solution. In the manufacture of dyes, such as indigo, the hardening of photographic films, the preservation of tissues (hardening the albuminous mate- rial), the manufacture of synthetic resins, such as Bakelite and "Redmanol " (see the chapter on phenol, p. 239), formaldehyde finds uses. The chart facing page 74 shows in detail the uses of formaldehyde. Ammonia and formaldehyde combine to form hexamethylene- tetramine: 6HCHO + 4HNH2 -- (CH2)6N4 + 6H20 commonly known as urotropine or " aminoform," which finds a wide use as a diuretic and urinary antiseptic, liberating formal- dehyde. It is believed that in the formation of sugars from carbon dioxide and moisture (in the plant kingdom), formaldehyde is an intermediate product. Emil Fischer, the eminent German chem- ist, has actually been able to obtain a sugar (acrose) from formal- dehyde, by treating the latter with barium or calcium hydroxide, thereby forming "formose " (a mixture of sugars), and isolating the acrose from the formose. We shall take this up again in the chapter on sugars. The conversion of formaldehyde into a sugar involves polymer- ization, and may be represented as 6HCHO -- C6H1206 Full scan of this foldout is at the end of this text