None
In the attempt to prepare them water is lost and an intramolecular anhydride formation takes place. The oxime-anhydrides are isomeric with the oxazoles, which also consist of five members ; hence their name, isoxazoles (B. 21, 2178 ; 24,39o;25,I787>. CH Isoxazole, Oxime-anhydride of Malonic Dialdehyde, \ \O, b.p. 95°, is prepared from propargyl aldehyde or /J-anilino-acrolein anil (p. 347) by hydroxyl- amine. Alcoholic alkalis convert it into cyanacetaldehyde (p. 401) (B. 36, 3665) : CH=CHv CH2.CHO 0 X | C=N ^- , 3--32, .. , y- sazoe, 3-y- C,HjNO, b.p. 118°, result from hydroxymethylene or formyl acetone. They are transparent liquids, having an intense odour resembling that of pyridine. a-Methyl isoxazole readily becomes rearranged into cyanacetone (q.v.) : CH=CHOH CH - CH CH - CO.CH3 CH - C.CH, I - > II ft y\\ II - > II ft y\\ CH,.CO NHa -«H20 CH3Ca N CHOH NH2 -2H2O CH« N ay-Dimethyl Isoxazole (CH3)2-ay-C8HNO, b.p. 141°, has a very peculiar odour, and is obtained from acetyl acetone and hydroxylamine hydrochloride. C. Dioximes. (a) Glyoximes or a-Dioximes. — When glyoxal, of which the monoxime is not known, pyroracemic aldehyde and the o-diketones are treated with hydroxylamine hydrochloride, the a-dioximes or glyoximes are formed. They can also be obtained from a-isonitroso-ketones or a-dichloroketones. The glyoximes form characteristic complex compounds with Ni, Co, Pt, Fe, Cu, which are stable and strongly coloured ; the metal is united to two glyoxime molecules (B. 39, 2692, 3382). Glyoxime, CH(=NOH).CH(=NOH), m.p. 178° (B. 17, 2001; 25, 705; 28, R. 620), is prepared from trichlorolactic acid (p. 368). Methyl Glyoxime, Acetoximic Acid, CH8C(NOH).CH(NOH), m.p. 153°. Dimethyl Glyoxime, Diacetyldioxime, CH3C(NOH).C(NOH)CH?, m.p. 234° (B. 28, R. 1006 ; J. pr. Ch. [2] 77, 414) is employed as a sensitive test for the presence of Ni.(Tr). Methyl Ethyl Glyoxime, CH3C(NOH).C(NOH).C2H5, m.p. 172° ((B. 34, 3978). Methyl Propyl Glyoxime, m.p. 168°. tert.-£«/y/ Glyoxime, (CH3)3C.C(NOH)- CH(NOH), m.p. 102°, is prepared from dichloropinacoline (p. 348). Methyl DIKETONES 355 Isobutyl Glyoxime, m.p. 170-172°. Higher homologues of glyoxime, see C. 1899, II. 524 ; 1904, II. 1700. (6) Glyoxime Peroxides (B. 23, 3496) result when NO2 acts on an ethereal CH3.C=N-O solution of the glyoximes : Dimethyl Glyoxime Peroxide, \ , b.p. 222°. CH3.C=N-O Methyl Ethyl Glyoxime Peroxide, b.p..,6 115°. (c) Furazanes, Azoxazoles, Furo-[a,&{\-diazoles are the anhydrides obtained CH:Nv from certain a-dioximes. Furazane, \ yO, itself is not known, whilst CH:N' dimethyl furazane, for example, has been prepared from diacetyl dioxime. (d) j8-Dioximes, Acetyl Acetone Dioxime, CH3C(NOH)CH2C(NOH)CH3> m.p. 150°, is produced from acetyl acetone by an excess of hydroxylamine. It easily gives this up and is converted into dimethyl isoxazole (see above). Reduc- tion by sodium and alcohol gives i,4-diaminopentane (p. 333). Electrolytic reduction in sulphuric acid solution leads to the formation of Dimethyl Pyrazo- lidine, CH3CH(NH)CH2CH(NH)CH3, a compound in which the nitrogen atoms have become united (B. 36, 219). (e) y-Dioximes, which may be systematically derived from the y-dialdehydes ; y-aldehyde-ketones and y-diketones may be prepared (i ) by the action of hydroxy- lamine on pyrrole (B. 22, 1968) and alkyl pyrroles (B. 23, 1788) ; (2-) from y-dike- tones and hydroxylamine. They are decomposed by boiling alkalis into the corresponding acids, or y-diketones ; the latter are far better obtained by means of nitrous acid. Succinaldehyde Dioxime, HON : CHCH2CH2CH : NOH, m.p. 173°, passes upon reduction into tetramethylene diamine (p. 333), and into succinic dialdehyde by the action of N2O3 (B. 35, 1184). Ethyl Succinaldioxime, HON : CHCH(C2H5)- CH2CH : N(OH), m.p. 135°. ; Propionyl Propionaldioxime, CH3CH2C : N(OH)- CH2CH2CH:N(OH), m.p. 85°. Methyl Lcevulinaldioxime, CH3C : N(OH)CH2- CH(CH)3CH : N(OH). Acetonyl Acetone Dioxime, CH3C : N(OH)CH2CH2C :- N(OH)CH3, m.p. 135°. uw-Diacetyl Pentane Dioxime, CH3C:N(OH)[CH2]5C :- N(OH)CH3, m.p. 172°. 3. Hydrazine and Phenylhydrazine Derivatives. CH3C-N Dimethyl Aziethane, \ I , m.p. above 270°, and Dimethyl bishydrazi- CH3C=N NH\ ,NH methylene, \ >C(CH,).C(CH3)< I , m.p. 158°, are obtained from diacetyl and NH/ XNH hydrazine (J. pr. Ch. [2] 44, 174). Dimethyl aziethane is also prepared from Diacetyl Acetylhydrazone, CH3C(N : N.COCH3) : C(OH)CH3, m.p. 167° by heating it with alkalis. The mono-semicarbazones of the a-diketones dissolve in alkalis, like the monoximes (p. 354), to a yellow solution. Diacetyl Semicarbazone, CH3COC(NNHCONH2)CH3, or CH2 : C(OH).C(NNHCONH2)CH3, m.p. 235°. Acetyl Propionyl Semicarbazone, m.p. 209° (B. 36, 3183°). Glyoxal Disemicarbazone (NH2CONHN : CH — )2, is a slightly soluble crystalline powder of high melting point (B. 40, 71). NH. .NH Glyoxal Bisguanidine, >C.NHN:CH.CH:NHNCf +H2O, m.p. 265, NH/ \NH2 with decomposition, is formed from dichloraldehyde (p. 203) and amidoguani- dine (A. 202, 284). Diacetyl Semicarbazone, m.p. 279°. Monophenylhydrazones. — Hydrazone of Pyroracemic Aldehyde, CH3CO.CH:- N.NH.C,H5, m.p. 148°, is obtained by hydrolyzing the reaction-product resulting from diazobenzene chloride and sodium acetoacetic ester with alcoholic sodium hydroxide (C. 1901, I. 299). Diacetylhydrazone, CH3CO.C:(NNHC6H6)CH3, m.p. 133°, has been prepared from diacetyl- and methyl-acetoacetic ester (Japp and Klingemann] (A. 247, 190). a- Acetyl Propionyl Hydrazone, CH3C(:NNHCftH6).COCH3, m.p. 97°, is obtained from acetyl propionyl. ft- Acetyl Propionyl Hydrazone, CH3CO.C:(NNHC6H5)CHt, m.p. 1 1 7*, is prepared from ethyl acetoacetic acid and diazobenzene chloride. 356 ORGANIC CHEMISTRY Diphenylhydrazones or Osazones. — Glyoxal (p. 346), methyl glyoxal (p. 348), the a-diketones and the a-isonitroso-acetones, when treated with phenylhydrazine, lose two molecules of water or water and hydroxylamine, respectively, and form diphenylhydrazones or osazones, which can also be obtained from a-hydroxyaldehydes, a-hydroxyketones, a-aminoaldehydes and a-aminoketones. The osazones have become especially important for the chemistry of the aldo- pentoses, and the aldo- and ketohexoses. The osazones are oxidized by potassium chromate and acetic acid to osotetrazones, which are converted by hydrochloric acid and ferric chloride into osotriazones : CH3C=N— NHC6H5 o CH3C=N— NC,H6 Fe2ci, CH3C=Nx igv^^j/t A^v^jiag .rcjv^j v/-n3v^=.L'i<y CH3C=N— NHC6H6 " CH3C=N— NC6H6 HC1 CH3C=N/ Diacetyl Osazone. Diacetyl Osotetrazone. Diacetyl Osotriazone. Glyoxal Osazone, C6H5NH.N:CHCH:N.NHC6H5, m.p. 177°, is also prepared from formaldehyde and phenylhydrazine, with the intermediate formation of CH:N.NC,H6 glycolyl aldehyde (p. 337) (B. 30, 2459). Glyoxal Osotetrazone, \ \ CH:N.NC8H6 m.p. 145° (B. 17, 2001 ; 21, 2752 ; 26, 1045). Methyl Glyoxal Osazone, C6H5NH.- N:C(CH3)CH:N.NHC6H5) m.p. 145° (B. 26, 2203). Methyl Glyoxal Osotetrazone, CH:N.N.C«H6 CH:N\ , m.p. 107°. Methyl Glyoxal Osotriazone, ^>NCeH5, CH3C=N.N.C,H6 CH3C=NX b.p.10 150° (B. 21, 2755). Diacetyl Osazone (formula above), m.p. 236° with de- composition (B. 20, 3184 ; A. 249, 203). Diacetyl Osotetrazone (formula above), m.p. 169° with decomposition. Diacetyl Osotriazone (formula above), m.p. 35°, b.p. 255° (B. 21, 2759). Acetyl Propionyl Osazone, m.p. 162° (B. 21, 1414 ; A. 247, 221). The i,3-diketones and the i,3-hydroxymethylene ketones (p. 343) unite with hydrazine and phenylhydrazine, forming pyrazoles (Vol. II.), which maybe regarded as derivatives "of the i,3-olefine ketols (A. 279, 237) : e.g. hydroxy- XH NH methylene acetone and hydrazine yield 3- Methyl Pyrazole, CH^ x:(CH,):N (B. 27, 954). Acetonyl acetone, a i,4-diketone, and phenylhydrazine yield: Acetonyl Aceto- CH:C(CH3k nosazone, m.p. 120°, and Phenylamido-Dimethyl-Pyrrole, \ yN.NHC,Hs, CH:C(CH3)/ m.p. 90°, b.p. 270° (B. 18, 60 ; 22, 170). a-Hydrazoximes. — Methyl Glyoxal Phenylhydrazoxime, CH3.C:N(NHC6H5).- CH : NOH, m.p. 134°, is prepared by the action of phenylhydrazine on iso- nitroso-acetoacetic acid. It parts readily with water and becomes methyl n- CH3C=NV phenyl osotriazole, | ">NC,H, ; (Vol. II.) (A. 262, 278). CH=N 7. ALCOHOL- or HYDROXY- ACIDS, CWH 2n<G)°IaH Acids of this series show a twofold character in their entire behaviour. Since they contain a carboxyl group, they are monobasic acids with all the attaching properties and reactions of the latter ; the OH-group linked to the radical bestows upon them all the pro- perties of the monohydric alcohols. As already indicated in the intro- duction to the dihydric compounds, these alcohols must be distinguished as primary, secondary, and tertiary, according as they contain, in addition to the carboxyl group, the group — CH2OH, characteristic of primary alcohols, the radical =CHOH, peculiar to the secondary alcohols, or the tertiary alcohol group =C.OH. This difference mani- fests itself in the behaviour of these bodies when subjected to oxidation. ALCOHOL- OR HYDROXY-ACIDS 357 However, the manner in which the alcoholic hydroxyl group in an alcohol-acid acts on the carboxyl group present in the same mole- cule depends greatly on the position of these two groups with refer- ence to each other. It is just this differentiating, opposing position of the two reactive groups which induces class differences of a distinctly new type, which are therefore made prominent because the oxidations undergone by primary, secondary and tertiary alcohols are already known to us. At present they are mostly termed hydroxy-fatty acids, because of their origin from the fatty acids by the replacement of a hydrogen atom by OH. The " Geneva names " are formed by the insertion of the syllable " ol," characteristic of alcohols, between the name of the hydrocarbon and the word "acid " ; CH2OH.COOH, hydroxyacetic acid, or [ethanol acid}. , Glycollic and ordinary or lactic acid of fermentation are the best- known and most important representatives. General Methods of Formation. — (i) Careful oxidation (a) of di- primary, primary-secondary and primary-tertiary glycols with dilute nitric acid, or platinum sponge and air : CH2.OH CH2.OH CH3CH.OH CH3CH.OH | +02=| +H20; | +02= | +HaO. CH2.OH COOH CH2OH COOH Glycol. Glycollic Acid. o-Propylene Glyco o- Lactic Acid. (b) By the oxidation of hydroxy aldehydes. (2) The action of nascent hydrogen (sodium amalgam, zinc and hydrochloric or sulphuric acid, sodium and alcohol, or electrolysis) on the aldehyde acids, the ketonic acids, and dicarboxylic acids. Pyroracemic Acid, CH3.CO.CO2H+2H=CH3.CH(OH).CO2H. Oxalic Acid, COOH.COOH + 4H=COOH.CH2OH+HaO. This reaction has been repeatedly used in preparing j3-, y- and 8-hydroxy-acids from J3-, y- and 8-ketone carboxylic esters. (3) Some fatty acids have OH directly introduced into them. This is accomplished by oxidizing them with KMnO4 in alkaline solution. Only acids containing the tertiary group CH (a so-called tertiary H-atom) are adapted to this kind of reaction (R. Meyer, B. 11, 1283, 1787 ; 12, 2238 ; A. 208, 60 ; 220, 56). Nitric acid effects the same as KMnO4 (B. 14, 1782 ; 16, 2318). (4) By heating unsaturated fatty acids with aqueous potassium or sodium hydroxide to 100° (A. 283, 50). (5) By the reaction of the monohalogen fatty acids with silver oxide, boiling alkalis, or even water. The conditions of the reaction are perfectly similar to those observed in the conversion of the alkylogens into alcohols. CH2C1C02H+H20=CH2(OH)COOH+HC1. The o-derivatives yield a-hydroxy-acids ; the ^-derivatives are occasionally changed to unsaturated acids by the splitting-off of a halogen acid, whilst the y-compounds form y-hydroxy-acids, which subsequently pass into lactones. y- Halogen acids are converted directly into lactones by the alkali carbonates. 35$ ORGANIC CHEMISTRY (6) By the action of nitrous acid on amido-acids : CH2(NH2).CO2H+HNO2=CH2(OH).CO2H+N2+H2O. Aminoacetic Acid. Hydroxyacetic Acid. (7) The hydroxy-acids can be obtained from the diazo-fatty acids, on boiling them with water or dilute acids. (8) From the a-ketone-alcohols — e.g. butyroin and isovaleroin (p. 342) — on treating them with alkalis and air. Nucleus-synthetic Methods of Formation. — (9) By allowing hydro- cyanic acid and hydrochloric acid to act on the aldehydes and ketones. At first hydroxy cyanides, the nitriles of hydroxy-acids (q.v.), are produced after which hydrochloric acid changes the cyanogen group into carboxyl : •i. Phase: CH8.CHO+HNC=CH3.CH<Q^ 2. Phase: CH3.CH<^+2H20=CH3.CH<^H4-NH,. a-Hydroxypropionic Acid. In preparing the hydroxycyanides, the aldehydes or ketones are treated with pure hydrocyanic acid, or powdered potassium cyanide may be added to the ethereal solution of the ketone, followed by the gradual addition of concentrated hydrochloric acid (B. 14, 1965 ; 15, 2318). The concentrated hydrochloric acid changes the cyanides to acids, the amides of the acids being at first formed in the cold, but on boiling with more dilute acid they undergo further change to acids. Sometimes the change occurs more readily by heating with a little dilute sulphuric acid. Ethylene oxide behaves like acetaldehyde with hydrocyanic acid. (TO) The glycol chlorhydrins (p. 319) undergo a similar alteration through the action of potassium cyanide and acids : 1. Phase: CH2(OH).CH2C1 + KNC =CH2(OH)CH2.CN + KC1, 2. Phase: CHa(OH).CH,CN-i-2HaO=CH2(OH).CH2.CO1H+NHI. /3-Hydroxypropionic Acid. (n) A method of ready applicability in the synthesis of a-hydroxy- acids consists in acting on diethyl oxalic ester with zinc and alkyl iodides (Frankland and Duppa). This reaction is like that in the formation of tertiary alcohols from the acid chlorides by means of zinc ethyl, or of the secondary alcohols from formic esters (p. 106) — i and 2 alkyl groups are introduced into one carboxyl group (A. 185, 184) : /O.C2H6 Zn(CH,)3 C/ ZnCH, CO2C2H6 C02CaH6 CO,C8HB CO2C2H5 Oxalic Ester. Dimethyl Oxalic Ester. C If we employ two alkyl iodides, two different alkyls may be intro- duced. The acids obtained, as indicated, are named in accordance with their deriva- tion from oxalic acid, but it would be more correct to view them as derivatives of hydroxyacetic acid or glycollic acid, CH2(OH).COaH, and designate, e.g. dimethyl oxalic acid, as dimethyl hydroxyacetic acid. (i2a) j8- Hydroxy-acids are formed when aldehydes or ketones are condensed with a-halogen fatty acid esters by means of zinc or magnesium ; e.g. propionic aldehyde and a-bromopropionic ester yield a-methyl j8-ethyl hydracrylic acid, ALCOHOL- OR HYDROXY-ACIDS 359 C2H5CH(OH)CH(CH3)COOH ; trioxymethylene, a-bromisobutyric ester and zinc yield aa-dimethyl hydracrylic acid (comp. p. 287) (C. 1901, I. 1196 ; II. 30 ; 1902, I. 856). (126) Ketone acid esters and magnesium alkyl iodides produce, in part, tertiary hydroxy-acid esters ; also, ethyl chloroglyoxylate with magnesium alkyl halides yields the oxalic ether of the a-hydroxy-acid ester (C. 190*2, II. 1359 ; 1900, II. mo) : CH3COC02C2H6+CH3MgI = (CH3)aC(OMgI)C02C2H6 2C2H6OCO.COCl+2CH3MgI=C2H6OCO.C(CH3)2O.CO.CO2C2H6+2MgClI. (13) When sodium or sodium ethoxide acts on the acetic esters and pro- pionic esters it converts them into j3-ketone-carboxylic esters, but in the case of butyric and isobutyric esters it produces the ether esters of £-hydroxy-acids, such as ethoxycaprylic ester, (CH3)2CH.CH(OC2H6).C(CH8)2CO2CaH6, from isobutyric ester (A. 249, 54). Cleavage-Reactions. — (14) The fatty acids are formed from alkyl malonic acids, CRR/(CO2R)2, by the withdrawal of a carboxyl group (p. 253), and the hydroxy-fatty acids are obtained in a similar manner from alkyl hydroxy malonic acids or tartronic acids : =CRH(OH).CO2H +CO2. Alkyl Tartronic Acid. Alkyl Hydroxyacetic Acid. Isomerism. — The possible cases of isomerism with the hydroxy- acids are most simply deduced by considering the hydroxy-acids as the mono-hydroxyl substitution products of the fatty acids. Then the isomers are the same as the mono-halogen fatty acids, which may be regarded as the haloid esters of the alcoholic acids corresponding with them. Hydroxyacetic or glycollic acid is the only acid which can be obtained from acetic acid : CH8.COOH CH2OH.COOH Acetic Acid. Glycollic Acid (p. 363). Propionic acid yields two hydroxypropionic acids : CH3CH2.CO9H CH3CH(OH).CpOH CH2(OH)CH2.COOH Propionic Acid. a-Hydroxypropionic Acid jB-Hydroxypropionic Acid ord. Lactic Acid (p. 362). Hydracrylic Acid (p. 369). These are distinguished as a- and jS-hydroxypropionic acids respectively. The a-acid contains an asymmetric' carbon atom, and therefore, theoretically, should yield an inactive variety, which can be resolved, and two optically active modifications : these, in fact, exist. Normal butyric acid yields three and isobutyric acid two mono-carboxylic acids : (CH3.CH2.CH(OH).C02H a-Hydroxybutyric Acid (p. 365) CH3.CH2.CH2UJ2hl CH3.CH(OH).CH2.C08H jS-Hydroxybutyric Acid (p. 370) tatync Acid. JCH2(OH).CH2.CH,.COOH y-Hydroxybutyric Acid (p. 374) rrr ( p53>C(OH).CO2H . . a-Hydroxyisobutyric Acid ™3>CH.C02H £g« (p. 365) Isobutyric Acid. | HOCH>CH-CO*H ' ' ' 0-Hydroxyisobutyric Acid (un- known). These alcohol-acids are divided into — Primary acids : Glycollic acid, hydracrylic acid, y-hydroxybutyric acid, jS-hydroxy- isobutyric acid. Secondary acids : a-hydroxypropionic acid, a-hydroxybutyric acid, /?-hydroxy« butyric acid. Tertiary acids : a-Hydroxyisobutyric acid. 360 ORGANIC CHEMISTRY Properties. — The hydroxy-fatty acids containing one OH group are, in consequence, more readily soluble in water, and less soluble in ether than the parent acids (p. 251). They are less volatile and, as a general rule, cannot be distilled without decomposition. Reactions. — (i) The alcohol-acids behave like the monocarboxylic acids, in that they yield, through a change in the carboxyl group, normal salts, esters, amides, and nitriles : COOK COOC2H, CONK, CN CH2OH CH2OH CH2OH CH2OH. (2) The remaining OH-group behaves like that of the alcohols, of which the hydrogen may be replaced by alkali metals and alkyls ; by acid radicals such as NO2, by the action of a mixture of con- centrated nitric and sulphuric acids ; or by a carboxylic acid residue, by the action of acid chlorides and anhydrides, such as the acetyl residue by means of acetyl chloride and anyhdride, CHj.CHONO, CHS.CHOCOCH, COOH COOH. Nitrolactic Acid. Acetyl Lactic Acid. Both of these reactions are characteristic of the hydroxyl groups of the alcohols (p. 323). (3) PC16 replaces the two hydroxyl groups by chlorine : COOH PC16 COCl + = | +2POC13+2HC1. CH2OH PC16 CH2C1 Glycollic Chloracetyl Acid. Chloride. The acid chlorides corresponding with the hydroxy-acids are not known. Instead of these we get the chlorides of the corresponding monochloro-fatty acids, in which the chlorine in union with CO is very reactive with water and alcohols, yielding free acids and their esters ; in the case cited, monochloracetic acid, CH2C1.CO2H, and its esters result. The remaining chlorine atom is, on the contrary, more firmly united, as in chlorethane. In addition to ethyl glycollic ester there are ethyl glycollic acid and ethyl etho-glycollic ester : COOC2H6 COOH COOC2Ht CH2.OH CH2.OC2H5 CHaOC2H5. Ethyl Glycollic Ethyl Glycollic Ethyl Etho-glycollic Ester. Acid. Ester. Alkalis cause the alkyl combined with CO2 to separate, forming ethyl glycollic acid. (4) The hydroxy-acids are reduced to their corresponding fatty acids (p. ^52) when they are heated with hydriodic acid. (5) Whilst in the preceding transpositions all the hydroxy-acids react similarly, the primary, secondary and tertiary alcohol-acids show marked differences when they are oxidized. STRUCTURE OF NORMAL CARBON CHAINS 361 (a) The primary hydroxy-acids yield, by oxidation, aldehyde acids : CO2H CO2H COOH CH2OH CHO COOH. Glycollic Acid. Glyoxylic Acid. Oxalic Acid. (b) The secondary hydroxy-acids yield ketone acids : the a-ketonic acids change to aldehyde and CO2, the j3-ketonic acids to ketones and CO2 : COaH COaH COt CH8CHOH CH3CO CH3CHO. (c) Tertiary a-hydroxy-acids yield ketones : (6) The a-hydroxy-acids undergo a similar decomposition when heated with dilute sulphuric or hydrochloric acid or by action of concentrated H2SO4. Their carboxyl group is removed as formic acid (when concentrated H2SO4 is employed. CO and HtO are the products) : (CH3)2C(OH)C02H = (CH3)2CO-f-HC08H CH3CH(OH)COaH=CH3.CHO+HC02H. Another alteration is undergone by the a-hydroxy-acids at the same time, which, however, does not extend far : water is eliminated, and unsaturated acids are produced. This change is easily effected when PC13 is allowed to act on the esters of a-hydroxy-acids (p. 291). (7) Especially interesting is the behaviour of the a-, /?-, y-, or 8-hydroxy- acids in respect to the elimination of water from carboxyl and alcoholic hydroxyl groups. (a) The a-hydroxy-acids lose water when they are heated and become cyclic double esters — the lactides — in the formation of which two molecules of the o-hydroxy-acid have taken part : COOH HO.CH.CH, CO.O.CH.CH3 I + I I +2H,0. CH3CHOH HOCO CHaCHO-CO o-Hydroxypropionic Acid or Lactic Acid. Lactide. (6) When the fi-hydroxy-acids are heated alone, water is withdrawn and un- saturated acids are the products (p. 291 ; C. 1897, I. 363) : CH2(OH).CH2C02H = CHa : CHCp.H+H.O. /3-Hydroxypropionic Acid Acrylic Acid. Hydracrylic Acid. (c) The y- and 8-hydroxy-acids lose water at the ordinary tempera- ture, and change more or less completely into simple cyclic esters — the y- and S-lactones. The a-, j8-, y- and 8-amido-carboxylic acids corresponding with the a-, /J-, y- and 8-hydroxy-acids, show differences similar to those manifested by the latter. STRUCTURE OF NORMAL CARBON CHAINS AND THE FORMATION OF LACTONES The peculiar differences in the behaviour of the a-, j8-, y- and 8-hydroxy-acids when they split off water have contributed to the development of a representation of the spacial arrangement or configuration of carbon chains (B. 15, 630). The 362 ORGANIC CHEMISTRY assumption that the atoms of a molecule not linked to each other in a formula cafl exert an affinity upon one another has led to the idea that, in a union of more than two C atoms, these atoms arrange themselves not in a straight line, but upon a curve. We can then comprehend that cyclic, simple ester formation can not take place between the first and second carbon atoms, rarely between the second and third, but readily between the first and fourth or first and fifth carbon atoms, which have approached so near to each other that an oxygen atom is capable of bringing about a closed ring (see Alkylene Oxide, p. 317, and Alkylene Imines, p. 334, as well as the strain theory of v. Baeyer in the introduction to the carbocyclic derivatives, Vol. II.). A. SATURATED HYDROXYMONO-CARBOXYLIC ACIDS, HYDROXY- PARAFFIN MONOCARBOXYLIC ACIDS a-Hydroxy-acids. (1) Gly collie Acid, Hydroxy acetic Acid [Ethanol Acid], CH2.OH.- COOH, m.p. 80°, occurs in unripe grapes and in the green leaves of Virginia creeper, Ampelopsis hederacea. History. — Glycollic acid was first obtained in 1848 by Strecker from amino- acetic acid or glycocoll — hence the name — according to the sixth method of formation (p. 358). In 1856 Debus discovered it together with glyoxal and glyoxylic acid among the oxidation products obtained from ethyl alcohol by the action of nitric acid. Wurtz in 1857 observed its formation in the oxidation of ethylene glycol, and Kehutt in 1858 showed how it could be made by boiling a solution of potassium chloracetate (A. 105, 286 ; comp. B. 16, 2414 ; A. 200, 75 ; B. 26, R. 606). It is also produced by the action of potassium hydroxide on glyoxal (p. 346) ; by the reduction of oxalic acid method of formation (No. 2, p. 357), and from diazoacetic ester (method of formation No. 7). Its nitrile results when hydrocyanic acid acts on formaldehyde (method No. 9), and is converted by hydrochloric acid into glycollic acid. It is also formed with hexamethylene tetramine when formaldehyde is warmed with KNC (C. 1900, I. 402). It also appears in the oxidation oi glycerol and dextrose by silver oxide. Glycollic acid crystallizes from acetone. It is very soluble in water and alcohol. Diglycollide and polyglycollide (p. 367) are produced when it is heated. Nitric acid oxidizes it to oxalic acid. When heated with concentrated sulphuric acid, glycollic acid decomposes into trioxymethylene (metaformaldehyde, p. 199), carbon monoxide and water). Calcium Salt, (CH2OHCO2) 2Ca +3H2O ; ethyl ester, CH2OH.CO2C2H5, b.p. 160°. Trichlorethyl alcohol (p. 117) can be regarded as being the chloride of orthogly collie acid. (2) Lactic Acid of Fermentation, a-Hydroxypropionic Acid, Ethyli- dene Lactic Acid, [d+l] Lactic Acid [2-PropanolAcid],CH3CH(OH)CO2H, m.p. 18°, b.p.12 120° (B. 28, 2597), is isomeric with fi-hydroxypropionic acid, hydr acrylic acid, [3-propanol acid], CH2OH.CH2CO2H, which will be discussed later as the first j3-hydroxy-acid. Lactic Acid is formed by a special fermentation, the lactic acid fermentation of lactose, sucrose, gum and starch. It is, therefore, contained in many substances which have soured — e.g. in sour milk, LACTIC ACID OF FERMENTATION 363 in sauerkraut, pickled cucumbers, common (or. lesser) centaury (Erythroca centaurium), also in the gastric juice. Methods of Formation. — The acid is artificially prepared by the methods already described : (i) from a-propylene glycol ; (2) from pyroracemic acid ; (5) from a-chloro- or bromo-propionic acid ; (6) from alanine ; (9) from acetaldehyde and hydrocyanic acid ; (13) by heating isomalic acid, CH3C(OH)(COOH)2 (B. 26, R. 7). Other methods of formation are : the action of heat on dextrose or sucrose with water and 2-3 parts of barium hydroxide at 160° ; prolonged contact of hexoses with dilute sodium hydroxide solution (B. 41, 1009) ; the interaction of pentoses, such as arabinose and xylose with warm potassium hydroxide solution (B. 35, 669); heating o-dichloracetone, CH3.CO.CHC12, with water at 200°. and oxidation of acetol (p. 341), all depend on the transformation of pyroracemic aldehyde. Lactic Acid Fermentation. — This fermentation is induced in sugar solutions by a particular ferment, the lactic acid bacillus, Bacillus acidi lacti, which is S resent in decaying cheese. It proceeds most rapidly at temperatures ranging :om 35° to 45° (C. 1 897, 11.338). It is noteworthy that the bacillus is very sensitive to free acid. The fermentation is arrested when sufficient lactic acid is produced, but is again renewed when the acid is neutralized. Therefore, zinc or calcium carbonate (C. 1897, II. 20, 937) is added at the beginning, and the lactic acid thus obtained either as the calcium or zinc salt. Should the fermentation con- tinue for some time, the lactic will pass into butyric fermentation, the insoluble calcium lactate will disappear, and the solution will at last contain calcium butyrate (comp. n-Butyric Acid, p. 259). On the formation of lactic acid as an intermediate product in the fermentation of dextrose to alcohol and CO8, see B. 37,421 ; A. 349, 125. History. — Scheele (1780) discovered lactic acid in sour milk. In 1847 Liebig demonstrated that the sarcolactic acid found by Berzelius (1808) in the fluids of the muscles was different from the lactic acid of fermentation. Wurtz (1858) described the formation of fermentation lactic acid from a-propylene glycol and air in the presence of platinum black, and recognized that it was a dibasic acid. Kolbe (1859) obtained lactyl chloride by the action of PC15 on calcium lactate. This body is identical with chloropropionyl chloride, and lactic acid is therefore monobasic and must be considered as hydroxypropionic acid. Later (1860) Wurtz called it a diatomic, monobasic acid, meaning to indi ate thereby that one of the two typical hydrogen atoms is more basic than the other. " But it is much more significant when KekuU declares that it is simultaneously an acid and an alcohol " (B. 20, R. 948). Strecker was the first to synthesize the acid from synthetic amidolactic acid or alanine, which had also been prepared by him through the interaction of hydrazonic acid and aldehyde ammonia. Fermentation lactic acid is a syrup soluble in water, alcohol and ether, and is optically inactive (C. 1905, II. 1527). Placed in a desic- cator over sulphuric acid, it partially decomposes into water and its anhydride. When distilled it yields lactide (p. 367), aldehyde, carbon monoxide and water. Heated to 130° with dilute sulphuric acid, it decomposes into alde- hyde and formic acid ; when oxidized with KMnO4, it yields pyro- racemic acid ; whilst with chromic acid, acetic acid and carbon dioxide are formed. Heated with hydrobromic acid, it changes to a-bromo- propionic acid. Hydriodic acid at once reduces it to propionic acid/ dad PC16 changes it into chloropropionyl chloride (p. 360). Lactates.—The sodium salt, CH3CH(OH)COaNa, is an amorphous mass. When heated with metallic sodium, disodium compound, CH8CH(ONa)CO2Na, results; calcium salt, (C,H6O8)aCa-f 5H2O, is soluble in ten parts of cold water, and is 364 ORGANIC CHEMISTRY very readily dissolved by hot water; zinc salt, (C3H6O3)2Zn-{-3H2O, dissolves in 58 parts of cold and 6 parts of hot water; iron salt, (C3H5O3)2Fe+3H2O. The chloride ofortholactic acid, CH3CH(OH)CC13, m.p. 50°, b.p. 161°, has already (p. 118) been referred to as trichlorisopropyl alcohol. It is also obtained from chloral by means of methyl magnesium iodide, and constitutes the soporific Isopral. With sodium ethoxide it forms ethyl a-ethyl lactate (p. 366) (C. 1904, I. 636 ; 1905, I. 344 ; B. 40, 212). The Optically Active Lactic Acids. The optically inactive, fermentation lactic acid contains an asym- metric carbon atom indicated in the formula CH3.CH(OH)C02H by the small star. The acid can be resolved by strichnine, morphine, or quinine, into two optically active components, — dextro-lactic (d-) acid and laevo-lactic (/-) acid, — possessing similar but opposite rotary power. The strychnine salt of the laevo-acid crystallizes out first, whilst the quinine salt of the dextro-acid is obtained first (B. 24, R. 794 ; C. 1906, I. 1150 ; II. 499). It must be noticed again here, that those optically inactive compounds which can be split into two optically active isomers or can be formed from these, are referred to as racemic [d-\-\] modifications (comp. p. 56). On mixing solutions of equal quantities of laevo- and dextro-lactate of zinc, the zinc salt of fermentation lactic acid will be produced, and, being more insoluble, will crystallize out. The dextro-modification will remain, if Penicillium glaucum is permitted to grow in the solution of inactive ammonium lactate (B. 16, 2720), whilst the laevo-rotatory modification is produced in the breaking down of a sucrose solution by Bacillus acidi Icevolactici (B. 24, R. 150). The active lactic acids are connected with the active a-bromo- propionic acids (p. 288) in the following manner : ^-bromopropionic acid with potassium hydroxide solution gives <Z-lactic acid ; silver carbonate, however, produces the /-acid ; the /-bromopropionic acid behaves vice versa (comp. Walden's Inversion, p. 55 ; and B. 100, "93) : KOH A rf-Bromopropionic acid >• 4-Lactic acid KOH /-Lactic acid > /-Bromopropionic acid ^-Alanine (^-a-aminopropionic acid, p. 389) yields, with nitrous acid, ^-lactic acid. This provides a link between d-lactic acid and tartaric acid, wherefrom the probable configuration for d- and /-lactic acid is obtained (comp. also p. 31 ; against this, however, B. 41, 894): COOH COOH HO— C— H H— C— OH P**"< CH, CH8 4-Lactic Acid. -Lactic Acid. On ^-alanine, /-serine, ^-glyceric acid, etc., see B. 50, 3718. Sarcolactic Acid, Dextro-lactic Acid, Paralactic Acid, was dis- covered in 1808 by Berzelius in the fluid of the muscles, and shown by HYDROXYVALERIC ACIDS 365 Liebig (1848) to be different from the lactic acid of fermentation. It is present in different animal organs, and is most conveniently obtained from Liebig's beef-extract. Sarcolactic acid is also formed during butyric fermentation (p. 259) by the granulo-bacillus and other butyric ferments (C. 1900, I. 777). Dextro- and laevo-lactic acid, m.p. 26° approx., are very hygroscopic bodies. Alkali converts the /-acid very rapidly into the [d+l] modification, whilst the d-acid is changed more slowly (C. 1904, II. 641). The rotation of an approximately 1*24 per cent, solution of the crystallized acid in water is ±2*24° (C. 1906, I. 1150). The dextro- and laevo-lactates of zinc crystallize with 2 molecules of water (C3H5O3)2Zn+2H2O. For other salts, see B. 29, R. 899. Zinc ^-lactate rotates the plane of polarization to the left, whilst the Mactate rotates it to the right : [a]f?= ± 8*6°. Homologous a- Hydroxy-acids. — The homologous a-hydroxy-acids are, from the very nature of things, either secondary or tertiary alcohol acids. Gly collie acid is the only primary a-alcohol acid. (a) The secondary alcohol acids are generally formed (i) from the corresponding a-halogen fatty acids (method 5) ; (2) nucleus-synthetic, from aldehydes and hydrocyanic acid, and subsequent saponification of the nitriles of the hydroxy-acids by means of hydrochloric acid (method 9). (b) The tertiary hydroxy-acids result — (r) From the oxidation of dialkyl acetic acid (general method 3). (2) Upon treating a-ketone alcohols with alkalis and air (method 8, p. 358). (3) By the action of hydrocyanic acid and hydrochloric acid on ketones (method 9). (4) When zinc and alkyl iodides react with oxalic ester (method n, p. 358). (5) From a-ketone-acid esters and magnesium alkyl halides (C. 1902, II. 1359). Hydroxybutyric Acids. — Four of the five possible isomers are known; two of these are a-hydroxy-acids : (i) a-Hydroxybutyric Acid, CH3CH2CH(OH)CO2H, m.p. 43°, has been resolved by brucine into its optically active components (B. 28, R. 278, 325, 725). (2) a-Hydroxyisobutyric Acid, Butyl Lactic Acid, Ace- tonic Acid, Dimethyl Oxalic Acid [2-~Methyl-2-propanol Acid], (CH3)2C(OH)COOH, m.p. 79°, b.p. 212°, is obtained from dimethyl acetic acid, from acetone and from oxalic ester (see above) ; hence the names acetonic acid and dimethyl oxalic acid. It is produced when jS-isoamylene glycol is oxidized by nitric acid, and is obtained from a-bromo- and a-amidobutyric acid as well as from amyl pyroracemate and CH3MgI, and from acetone chloroform. It occurs in the urine during acetonuria (C. 1899, II. 63). Acetone Chloroform, (CH3)2C(OH)CC13, m.p. 91°, b.p. 167°, is obtained by the union of acetone and chloroform in the presence of alkali hydroxides. It is a derivative of a-hydroxyisobutyric acid, the chloride of ortho-a-hydroxyisobutyric acid (p. 235) which stands in the same relation to a-hydroxyisobutyric acid that chloroform does to formic acid. Aqueous alkalis convert it into a-hydroxyl- isobutyric acid (Willgerodt, B. 20, 2445 ; 29, R. 908 ; C. 1898, II. 277 ; 1902, I. 176). It acts as an anaesthetic and an antiseptic. In the presence of phenols and sodium hydroxide solution, acetone and chloro- form yield a-phenoxyisobutyric acids, C2H5OC(CH3)2COOH (C. 1916, II. 326). a-Hydroxy valeric Acids : a-Hydroxy-n-valeric Acid, CH3.CH2.CH2.CH(OH).CO2H, m.p. 28-29° (B. 18, R. 79)- a-Hydroxyisovaleric Acid, (CH3)2.CH.CH(OH).CO2H, m.p. 86°, is prepared from dimethyl pyroracemic acid (p. 408) (A. 205, 28 ; B. 28, 296 ; C. 1902, I. 251). Methyl Ethyl Glycollic Acid, CC23>C(OH).CO2H, m.p. 68° (A. 204, 18). a-Hydrpxycaproic Acids, a-Hydroxy-n-caproic Acid, CH3[CH2]3CH(OH)COqH, m.p. 61°, is prepared from a-bromo- or a-amino-n-caproic acid. a-Hydroxy-iso- 366 ORGANIC CHEMISTRY caproic Acid, Leucic Acid, (CH3)2CH.CH2CH(OH)COOH, m.p. 73°, is obtained, from leucine (p. 389) by means of nitrous acid (Strecker, 1848). a-Hydroxy-diethyl Acetic Acid, Diethyl Oxalic Acid, (CaH5)2C(OH).COOH, m.p. 80° (A. 200, 21). a-Hydroxy-methyl Isopropyl Acetic Acid, (CH8)2CH.C(CH3)(OH)COOH, m.p. 63° (C. 1898, I. 202). a-Hydroxy-tert, -butyl Acetic Acid, (CH3)2C.CH(OH)COOH, m.p. 87°, is obtained from trimethyl pyroracemic acid (p. 408) by reduction. Higher a-Hydroxy-fatty Acids: fi-Diethyl Ethylidene Lactic Acid, (CjHj),- CH.CH(OH)COOH, m.p. 82°, is prepared from y-bromo-y-acetoxy-a-diethyl acetoacetic ester, (C2H5)2C(COOR)CO.CHBr(OCOCH3), by means of the cleaving influence of dilute sulphuric acid (B. 31, 2953). a-Hydroxy-n-caprylic Acid, CH3[CH2]5CH(OH)COOH, m.p. 69-5°, is obtained from cenanthol. Di-n-propyl Glycollic Acid,a-Hydroxy-di-n-propyl Acetic Acid, (C3H7)2C(OH)COOH, m.p. 72°, is prepared from butyroin (p. 342) (B. 23, 1273). Di-isopropyl Oxalic Acid, a-Hydroxy-di-isopropyl Acetic Acid, (C3H7)C(OH)COOH, m.p. 111° (B. 28,2463). Di-isobutyl Glycollic Acid (C4H9)2C(OH)COOH, m.p. 114°. Methyl Nonyl Glycollic Acid, (C9H19)C(CH3)(CH)COOH, m.p. 46°, is obtained from methyl nonyl ketone (C. 1902, I. 744). a-Bromo -fatty acids have yielded the following: a-Hydroxylauric Acid, C18H22(OH)COOH, m.p. 74° (C. 1904, I. 261) ; a-Hydroxymyristic Acid, C13H26- (OH).CO2H, m.p. 51° (B. 22, 1747) ; a-Hydroxy palmitic ^drf,C16H30(OH)CO2H, m.p. 82° (B. 24, 939) ; a-Hydroxystearic Acid, C17H34(OH)CO2H, m.p. 85° (B. 24, 2388). In the following pages those a-hydroxy-acid derivatives will be described which belong to glycollic and lactic acids. Alkyl Derivatives of the a-Hydroxy-aeids. A single a-hydroxy-acid yields three kinds of alkyl derivatives : ethers, esters and ether-esters : COOH COOH COOC2H5 COOC2H6 CH2OH CH2OC2H5 CH2OH CH2OC2H6. Glycollic Ethyl Glycollic Glycollic Ethyl Ethyl Glycollic Acid. Acid. Ester. ' Ethyl Ester. (1) The alkyl-ethers of the a-hydroxy-acids are obtained (i) by the action of sodium alcoholates on salts of the a-halogen substitution products of the fatty acids ; (2) by the saponification of the dialkyl ether esters or alkyl ether nitriles (p. 380) of the a-hydroxy-acids. Methyl-ether Glycollic Acid, CH3OCH2.COOH, b.p. 198°. Ethyl Glycollic Acid, b.p. 206-207°; chloride, b.p. 128° (J. pr. Ch. [2] 65, 479 ; C. 1907, I. 871). a-Ethoxyl Propionic Acid, CH3CH(OC2H5).CO2H, b.p. with partial decomposition 195—198°. It is split up by means of cinchonidine or morphine into its two optical components, which are remarkable for their large rotations. (2) Alkyl Esters of the a-hydroxy-acids result (i) on heating the free acids with absolute alcohol ; (2) when the cyclic double esters, the lactides, are heated with alcohols. Glycollic Methyl. Ester, CH2(OH)COOCH3, b.p. 151°. Glycollic Ethyl Ester, b.p. 160°. Lactic Methyl Ester, CH3CH(OH)CO2CH3, b.p. 145°. Lactic Ethyl Ester, b.p. 154-5°. (3) The dialkyl-ethyl esters of the a-hydroxy-acids are produced (i) when sodium alcoholates act on the esters of a-halogen fatty acids ; (2) by the interaction of alkylogens and the sodium derivatives of the alkyl esters of the a-hydroxy-acids. ' Methyl Glycollic Methyl Ester, CH2(OCH3).COOCH3, b.p. 127° ; ethyl ester, b.p. 131°. Ethyl Glycollic Methyl Ester, CH2(O.C2H5)CO.OCH3, b.p. 148°. Ethyl Glycollic Ethyl Ester, b.p. 152° (B. 17, 486). Methyl Lactic Methyl Ester, CHSCH(OCH8)COOCH3, b.p. 135-138°; ethyl ester, b.p. 135-5°. Ethyl Lactic Ethyl Ester, CH8.CH(OC2H5).COOC2H6, b.p. 155° (A. 197, 21 ; B. 40, 212). Anhydride Formation of the a-Hydroxy-Acids. Since the a-alcohol-acids possess the characteristics of both car- boxylic acids and alcohols, they are capable of forming various types of anhydrides. These may occur between the alcoholic groups of two molecules (dicarboxylated ethers or ether acids), between the carboxylic ANHYDRIDES. LACTIDES 367 groups, between the alcoholic groups (dihydroxylated carboxylic anhydrides and ether carboxylic anhydrides), and, finally, between the alcohol group of one molecule and the carboxylic group of a second (alcohol ester acids or semilactides and cyclic double esters or lactides). The best example for examination is glycollic acid. PT-T /"'/"lOW *• °<CH COOH Alcoho1 anhydride of glycollic acid : Diglyeollic Acid. 2l HOCH2CO>° G1ycollic anhydride is not known. 3- O<S52£2>O Alcohol- and acid-anhydride of glycollic acid : Diglyeollic Anhydride. 4' HOCO CH >° Open ester acid : Glycoll°-Slycollic Acid. 5- CKrnrw^0 Closed, cyclic double ester of glycollic acid: Glycollide, H* simplest Lactide. Diglyeollic Acid, the alcohol anhydride of glycollic acid, C4H6O5, is formed together with glycollic acid on boiling monochloracetic acid with lime, baryta, magnolia, or lead oxide, and in the oxidation of diethylene glycol, O<CrM2 rw n (p. 313). Diglyeollic acid crystallizes with water in large rhombic prisms. CTT CO Diglyeollic Anhydride, O<Q|JiCQ>O> m.p. 97°, b.p. 240°, is isomeric with glycollide. It is obtained from glycollic acid by a simultaneous alcohol-anhydride and acid-anhydride formation. It also results upon heating diglycollic acid, or by boiling it with acetyl chloride (A. 273, 64). Dilactylic Acid, O(CH3CHCOOH)2, has received little attention. Glycoiloglycollic Acid, CH2(OH)COOCH2COOH, generally termed glycollic anhydride, and Lactylolactic Acid, CH3CH(OH)COOCH(CH3)COOH, commonly called lactic anhydnde, have not been well studied. They are produced when the free a-hydroxy-acids are heated to 100°, and constitute intermediate steps in the lactide formation (B. 23, R. 325). Distillation of lactic acid produces lactyl lactic acid, lactide, and also Lactyl Acetyl Lactic Acid, CH3CH(OH)COOCH- (CH3)COOCH(CH3)COOH, m.p. 39°, b.p. 235-240° (C. 1905, I. 862). Lactides : Cyclic Double Esters of the a-Hydroxy-acids. CH CO Digly collide, O<XCQCH '>®' m'p* 86°' is Procluced when polyglycollide is distilled under greatly reduced pressure. When heated at the ordinary pressure, or if kept, it reverts to polyglycollide, from which it differs by its lower melting point and ready solubility in chloroform. It combines readily with water (A. 279, 45). Polyglycollide, (C2H2O2)x, m.p. 223°, is formed on heating glycollic acid, and when dry sodium chloracetate is heated alone to 150°. It passes into glycollic esters when heated with alcohols in sealed tubes (A. 279, 45). Lactide, O^oCH^CEn^0' m>p> I25°' b-p>'6<> 255°' b<pll2 I38° (B- 28» 2595), results on heating lactic acid under diminished pressure. It can be recrystallized from chloroform (A. 167, 318; B. 25, 3511 ; 28, 2595). d- and l-Lactide, m.p. 95° (C. 1906, I. 1329). The optical rotation of the lactic acids is increased greatly by lactide formation. Homologous lactides, see B. 26, 263 ; A. 279 100. COO v Cyclic Ether Esters. — Glycollic Methylene Ester, \ /CH2, is obtained from CHaO/ glycollic acid and formaldehyde (C. 1901, II. 1261). Glycollic Ethylene Ester, COOCHa m.p. 31°, b.p. 214° (B. 27, 2945)- CH2OCH,' COO. Methylene Lactate, >CH2, b.p. 153° (B. 28, R. 180). CH,CHO/ 368 ORGANIC CHEMISTRY coox Lactic Ethylidene Ester, >CH.CH8, b.p. 151°, is produced when CH.CHCK lactic acid and acetaldehyde are heated to 160°. Its hexachloro-derivative is chloralide (below). Acid Esters of the a-Hydroxy-aelds. Nitroglycollic Acid, m.p. 54°, results, together with nitroglycollyl gly collie acid, NO2OCH2COOCH2COOH, from glycollic acid and nitrosulphuric acid'. Nitrolactic Acid, CH8CHO(Npa)COOH, is a yellow liquid, decomposing at the ordinary temperature into oxalic and hydrocyanic acids (B. 12, 1837 ; C. 1903, II. 488 ; 1904, 1. 434). Mono-halogen acetic acid (p. 287) and a-halogen propionic acid (p. 288) are looked on as being haloid acid esters of a-hydroxy-acids. Acetyl Glycollic Acid, CH2O(COCH3)COOH, m.p. 67°, b.p.12 145°, is obtained from glycollic acid and acetic anhydrides ; chloride, b.p.14 54° ; ethyl ester, CH2O(COCH3)COOC2H6> b.p. 179°. Acetyl Lactic Acid, CH3CH(OCOCH3)- COOH, m.p. 57-60°, b.p.n 127°, is prepared from lactic acid and acetyl chloride ; chloride, b.p.u 56° (B. 36, 466 ; 37, 3971 ; 38, 719; C. 1905, I. 1373). Halogen a-Hydroxy-acids. j8-Monohalogen Ethylidene Lactic Acids.— p-Chlorolactic Acid, CH2C1CH- (OH)CO2H, m.p. 78°. fl-Bromolactic Acid, CH2BrCHOHCO2H, m.p. 89°. fi-Iodolactic Acid, CH2ICH(OH)CO2H, m.p. 100°. These three acids have been prepared by adding hydrogen chloride, bromide or iodide to epihydrin or glycidic acid, CH8CH(O)CO2H. j8-Chlorolactic acid is also formed from monochloraldehyde by the action of hydrocyanic acid and by the oxidation of epichlorhydrin, CHaCH(O)CHaCl, and a-chlorhydrin, CH2C1CH(OH).CH2OH, with concentrated HNO, ; as well as by the addition of hypochlorous acid to acrylic acid (together with a-chlorhydra- crylic acid). Silver oxide converts it into glyceric acid ; when reduced with hydriodic acid it becomes /J-iodopropionic acid. Heated with alcoholic potassium hydroxide it is again changed to epihydric acid (see above), just as ethylene oxide is obtained from glycol chlorhydrin (p. 317). Higher halogen substitution products of the a-hydroxy-acids have been prepared by the progressive treatment of halogen aldehydes, like di- chloraldehyde, chloral, bromal, and trichlorobutyric aldehyde, with hydrocyanic acid and hydrochloric acid. Trichlorolactic acid has been the most thoroughly studied. B-DichlorolacticAcid, CHC12.CH(OH).CO2H, m.p. 77°. /3-Trichlorolactic Acid, CC13.CH(OH)CO2H, m.p. 105-110°, is soluble in water, alcohol and ether. Alkalis easily change it into chloral, chloroform and formic acid. Zinc and hydrochloric acid reduce it to dichlor- and mono-chloracrylic acids (p. 294). Because trichlorolactic acid yields chloral without difficulty, it is converted quite readily, by different reactions, into derivatives of chloral, and also of glyoxal, probably by decomposition into dichloraldehyde and CO2. It forms glyoxime with hydroxylamine, and glycosin with ammonia (p. 346, and B. 17, 1997)- Trichlorolactic Ethyl Ester, CC18CH(OH)COOC2H6, m.p. 66°, b.p. 235°, is prepared from chloral cyanhydrin with alcohol and sulphuric or hydrochloric acid (B. 18, 754). Chloralide, Trichlorethylidene Trichlorolactic Ester, CC13.CH<CQ >CH.CC1,, m.p. 114°, b.p. 272°, was first prepared by heating chloral with fuming sulphuric acid to 105°, and subsequently when trichlorolactic acid was heated to 150° with HYDRACRYLIC ACID 369 excess of chloral. When heated to 140° with alcohol, it breaks up into trichloro- lactic ester and chloral alcoholate (W attach, A. 193, i). Chloral also unites with lactic and other hydroxy-acids, glycollic, malic, salicylic, etc., forming compounds very similar to that with trichlorolactic acid, known as Moralities (A. 193, i). Tribromolaetic Acid, CBr3.CH(OH)CO2H, m.p. 141-143°, unites with chloral and bromal to corresponding chloralides and bromalides. Triehlorovalerolaetic Acid, CH3CC12CHC1.CH(OH).CO2H, m.p. 140° (A. 179,99). /J-Hydroxycarboxylic Acids. Generally the j3-hydroxycarboxylic acids, when heated, part with water and become converted into unsaturated olefine carboxylic acids : — H2o CH2OH.CH2.C02H > CH2=CHC02H. Ethylene Lactic Acid or Hydracrylic Acid. Acrylic Acid. In the case of the higher homologues of ethylene lactic acid, when water is eliminated, both aj3- and j8y-olefine carboxylic acids (B. 26, 2079) result. a-Dialkyl ^-Hydroxy-acids and their esters are prepared from the dialkyl acetoacetic esters by reduction, and from aldehydes, a-bromo- dialkyl acetic esters by zinc. Those which possess no hydrogen atom in the a-position free to take part in the splitting off of water decompose in various ways : when heated, some are converted into a mixture of aldehydes and dialkyl acetic acids ; others yield semi- lactides, such as the a-hydroxy-acids (p. 366) (C. 1904, I. 1134) : CH3CH(OH)C(C2H5)2COOH =CH3CHO +CH(C2H6)2CC>9H a-Diethyl-0-hydroxybutyric Acid. Diethyl Acetic Acid. CH2(OH)C(CH3)2COOH Hydroxypivalic Acid. > CH2(OH)C(CH3)2COO[CH2C(CH3)2COO]4CH2.C(CH3)aCOOH The esters of such acids containing free hydrogen atoms attached to a carbon atom in the y-position react with P2O5 in a benzene solu- tion and form j8y-olefine carboxylic acids ; in other cases atomic wandering occurs, and a/?-olefine carboxylic acids result (pp. 293, 371) (C. 1906, I. 999 ; II. 318). j8-Hydroxyacids are produced (i) in the oxidation of primary-secondary and primary- tertiary glycols ; (2) (p. 357) by the reduction of j3-ketone carboxylic esters (secondary hydroxy-acids); and (3) on boiling j3y- or A2-olefine carboxylic acids with sodium hydroxide. Furthermore, zinc and the esters of the mono halogen fatty acids — e.g. bromisobutyric ester — combine with aldehydes (isobutyl aldehyde) to form secondary /J-hydroxy -acids, and with ketones to form tertiary /J-hydroxy- acids (B. 28, 2838, 2842 ; C. 1906, 1. 999 ; II. 318). In these reactions the following stages can be recognized : — I. CH2Cl.C02R'+Zn=CH2(ZnCl)COOR' II. CH2( III. (C2 Ethylene Lactic Acid, Hydracrylic Acid [3-Propanol Acid], CH2(OH).CH2.CO2H, is isomeric with ethylidene lactic acid or the lactic acid of fermentation, and is obtained (i) by the oxidation of trimethy- lene glycol ; (2) from j8-iodopropionic acid, or /?-chloropropionic acid, with moist silver oxide ; (3) from acrylic acid by heating with aqueous VOL. I, 2 B 370 ORGANIC CHEMISTRY sodium hydroxide to 100° ; (4) by the saponification of ethylene cyanhydrin with hydrochloric acid. This reaction completes the synthesis of ethylene lactic acid from ethylene : CHaCN CHaCOaH CHjOH CH,OH CHa CHa The free acid forms a non-crystallizable, thick syrup. When heated alone, or when boiled with sulphuric acid (diluted with i part H2O), it loses water and forms acrylic acid (hence the name hydra- crylic acid). Hydriodic acid again changes it to jS-iodopropionic acid. It yields oxalic acid and carbon dioxide when oxidized with chromic acid or nitric acid. The sodium salt, CHa(OH)CHaCOaNa, m.p. 142-143°, and the calcium salt, (CaHtO,)aCa+2HaO, m.p. anhydrous 140-150°, when heated above their melting points pass into the corresponding acrylates. The zinc salt, (C3H5O3)2Zn4-4HaO, is soluble in water and alcohol, whereas the latter precipitates zinc salts of the isomeric acids. p-Amyloxypropionic Acid, C,HuOCH,CHaCOOH, b.p.,0 140°, yields the diamyl-ether of tetramethylene glycol, when its sodium salt is electrolyzed (p. 315) (C. 1905, I. 1698). j8-Hydroxybutyric Acid, [3-Butanol Acid], CH3CH(OH)CHaCOaH, is formed (i) by the oxidation of aldol (p. 338) ; (2) by the reduction of acetoacetic ester (p. 416) with sodium amalgam ; (3) from a-propylene chlorhydrin, CH3CH(OH)- CHaCl, by the action of KNC and subsequent hydrolysis of the cyanide. It is a thick oil and is volatile in steam. Heat decomposes it into water and crotonic acid, CH3.CH : CHCOOH. Conversely, crotonic ester unites with alcohol in the presence of CaH,ONa to form /3-ethyoxy butyric ester, C2H6O.CH(CH3)CH2- COaR (B. 33, 3329). The racemic acid is split by means of its quinine salts ; the tot/o-rotatory component [a]D=— 24-9° is separated out, and the ^^o-rotatory component is obtained from the mother liquor. An optically active j8-hydroxy- butyric acid has been isolated from diabetic urine (B. 18, R. 451). p-Hydroxyisobutyric Acid, HOCH2CH(CH3).COaH, is not known. p-Hydroxy-n-valeric Acid, CH3CH2CH(OH).CH2CO2H (A. 283, 74, 94). a-Methyl p-Hydroxybutyric Acid CH3CH(OH)CH(CH8)CO2H (A. 250, 244). a-Ethyl Hydracrylic Acid, is a syrup: ethyl ester, b.p. ,s 96°, is obtained from trioxymethylene and a-bromobutyric acid in benzene solution with zinc (C. 1905, II. 45, 540). p-Hydroxyisovaleric Acid, (CH3)2C(OH)CH2.CO2H, results when isobutyl formic acid is oxidized with KMnO4 (A. 200, 273). a-Dimethyl Hydra- crylic Acid, Hydroxypivalic Acid, HO.CHaC(CH8)2COOH, m.p. 124° ; ethyl ester, b.p.lt 86°, is obtained from trioxymethylene, bromisobutyric ester and zinc (C. 1902, I. 643). Acetoxypivalic chloride (C. 1908, I. 1531). p-Hydroxy-n-caproic Acid, CH8CH2CH2CH(OH)CH2COaH, is formed on boiling hydrosorbic acid with sodium hydroxide (A. 283, 124). a-Ethyl B- Hydroxybutyric Acid, CH3CH(OH)CH(C2H6)CO2H (A. 188, 240). a-Methyl B- Hydroxyvaleric Acid, CH,CHaCH(OH)CH(CH3)CO2H (B. 20, 1321). p-Hydroxyisocaproic Acid, (CH8)aCHCH(OH)CHaCOaH (B. 29, R. 667). PP~ Methyl Ethyl Hydracrylic Acid is obtained by oxidation of methyl ethyl allyl carbinol (C. 1900, I. 1069), a-Methyl p-Ethyl Hydracrylic Acid is a syrup. a-Methyl a-Ethyl Hydracrylic Acid, m.p. 56°. a-Propyl Hydracrylic Acid is a syrup. a-Isopropyl Hydracrylic Acid, m.p. 64°. aap-Trimethyl Hydracrylic Acid, m.p. 31°, b.p.15 148°, is obtained as an ester (method of formation, No. 12, p. 358). p-Hydroxyisoheptylic Acid, (CH,)aCHCHaCH(OH)CHaCOaH, m.p. 64° (A. 283, 143). LACTONES 371 fi-Methyl Pvppyl Ethylene Lactic Acid, (CH3)(C3H7)C(OH)CH2COaH, is pro- duced in the oxidation of methyl allyl propyl carbinol (J. pr. Ch. [2] 23, 267). fi-Diethyl Ethylene Lactic Acid, (C2H8)2C(OH)CH2CO2H, results from the oxidation of diethyl allyl carbinol (J. pr. Ch. [2] 23, 201) (p. 124). a-M 'ethyl Ethyl p-Hydroxybutyric Acid, CH3CH(OH)C(CH3)(C2H6)CO2H (A. 188, 266). Tetramethyl Ethylene Lactic Acid, (CH3)2C(OH)C(CH3)2CO2H, m.p. 152°, is pre- pared from acetone bromisobutyric ester and zinc. It yields CO2 and dimethyl isopropyl carbinol when heated. The ester and P2O6 yield dimethyl isopropenyl acetic acid (B. 28, 2829 ; C. 1906, I. 909). ^-Dimethyl ft-Ethyl Hydracry lie Acid, C2H6CH(OH)C(CH3)2COOH, m.p. 103° (C. 1901,!. 1196). B-Hydroxyiso-octylic Acid, (CH3)2CHCH2CHaCH(OH)CHaC02H, m.p. 36° (A. 283, 287). a-Methyl Propyl fi-Hydroxybutyric Acid, CH3CH(OH)C(CH3)(C3H7)CO2H (A. 226, 288). a-Diethyl fi-Hydroxybutyric Acid, CH3CH(OH)C(C2H6)2CO2H (A. 201, 65 ; 266, 98). a-Dimethyl fi-Isopropyl Ethylene Lactic Acid, (CH3)2CH.CH(OH).- C(CH3)2.CO2H, m.p. 92° (B. 28, 2843), is obtained also by oxidation of the corre- sponding glycol (p. 316) or aldol (p. 373) (C. 1902, I. 461). 