2808 CLOUGH OPTICAL ROTATORY POWERS AND RELATIVE CCCLXXXVI1.-The Relationship between the Opticat Rotatory Powers and the Relative Configurations of Optically Active Compounds. Part I I . The Relative Configurations of the Optically Active Mandelic Acids and P-Phenyl-lactic Acids. By GEORGE WJLLIAM CLOUGH. IN Part I * (J. 1918 113 526) it was shown that t,he formation of similar derivatives from the configuratively related compounds, Z-lactic acid Z-glyceric acid d-malic acid and d-tartaric acid was usually accompanied by changes of the same character in their optical rotatory powers. It was therefore assumed that as a rule, the introduction of the same substituent into similarly constituted, optically active compounds possessing the same relative con-figurations produced alterations of the same character in their optical rotatory powers.The somewhat vague term “ similarly constituted compounds ” was used in this connexion since it was not (and still is not) possible to state precisely the extent of the applicability of the rule. It applies to the members of such homo-logous series of optically active compounds as the aliphatic normal secondary alcohols and the simple a-hydroxy-acids. Indeed the higher members of a homologous series being derivatives from the lower members the rule would indicate that the optical rotatory powers of those optically active members of a series which are configuratively related would lie approximately on a curve. But not only do regularities occur in the optical rotatory powers of members of homologous series they are evident (with few excep-tions) in those of correspondmg derivatives from the optically active mono- and di-hydroxy-propionic and -succinic acids.The application of the principle to d- a-hydroxybutyric acid left no doubt that this compound possessed the same configuration it8 E-lactic acid but the same confidence could not be felt in the con-clusions which were drawn from the optical rotatory powers of compounds in which a phenyl or benzyl group was attached to the asymmetric carbon atom. In an endeavour to fix definitely the Errata in Part I Page 532 line 5 from bottom f o r “ X=Bz Y=Me ” read ‘‘ X=Bz Y=Et.” Page 532 last line for “ -123.6 ” read “ -247.” Page 640 line 3 for “ +50-6” ” read “ - 5 0 - 6 O . ” Since this paper was submitted for publication the author’s attention haa been directed to a paper by Freudenberg and Markert entitled “ Die Konfigur-ation der Mandekaure ” (Ber.1925,58 1753). These authors have employed the method indicated in Part I and have confirmed the suggestion made therein concerning the configurations of the optically active mandelic acide CONFIGURATIONS OF OPTICALLY ACTIVE COMPOIMDS. 2809 confipllrations of the optically active forms of mandelic and p-phenyl-lactic acids the optical rotatory powers of these compounds and some of their derivatives are considered in the present communi-cation. The measurement by Freudenberg Brauns and Siege1 (Ber. 1923 56 199) of the speciiic rotation of the amide of I-hexa-hydromandelic acid (prepared from I-maadelic acid) enabled those workera to confirm the suggestion that I-mandelic acid is a “ d ,’-a-hydroxy-acid (Part I p.534). (For compounds containing one asymmetric carbon atom it appears to the present author desirable to retain the prefixes d- and I- with their conventional significance, but to denote their relative configurations by the prefixes “ d ”- and “ I ”-; Ioc. cit. p. 534.) The optical rotatory powers of other derivatives from I-hexahydromandelic acid and from I-mandelic acid definitely indicate that these acids belong to the “ d ”- aeries of a-hydroxy-acids. This result is of importance in that it enables us to determine the configurations of I-benzoin the related optically active glycols and of amygdalin with reference to that of d-tartark acid.The experimental data quoted in tables I-V are also in the author’s opinion sufficient to justify the allocation of d- p-phenyl-lactic acid to the “ d ” - series of a-hydroxy-acids. If this con-clusion is accepted it is possible to assign configurations to the glycols derived from this acid and also to the four optically active phenylglyceric acids (provided the assumption is made that cis-addition of hydroxyl occurs on oxidation of the cimamic acids; compare Berner and Riiber Ber. 1921 54 1945). The molecular rotations of the standard “ d ”- acids in aqueous solution are lower * than those of the corresponding sodium (pow-ium or ammonium) salts (Table I). The same regularity is observed in the molecular rotations of I-hexahydromandelic acid I-mandelic acid d- P-phenyl-lactic acid and their salts.The molecular rotations of the lower esters of the same acids increase as the molecular weights of the esters increase (Table PI). The measurements by Wood and his collaborators of the optical rotatory powers and the optical dispersive powers of the optically active alkyl lactates and hexahydromandelates at various tem-peratures are especially valuable in comexion with the subject of this investigation. The molecular rotations of the amides of the same acids compared with those of the methyl esters further illustrate the relation of Throughout this paper an ’‘ incresse ” of rotation denotes an jncreaae inthe numerical value of a destrorotation or a decrease in the numerical value of a laevorotation. For the sake of clearness the tabulated valnes are given for the “d77-forms although in some ~ ~ J B S the measuremente wem actually made on the anentiomorphous forms 2810 CLOUGH OPTICAL ROTATORY POWERS AND RELATIVE Z-mandelic acid and of d-p-phenyl-lactic acid to the standard " d "-a-hydroxy-acids (Table 111).TABLE I. The Molecular Rotcations ([MID) of Some O p t i d l y Active Or-Hydroxp acids in Aqueous Xolution. Z-Lactic acid. 2-Glyceric acid. d-Mdic aid. d-Tartaric acid. Z-Heuahydro -Z-Mandelic acid. mandelic acid. d-p-Phenyl-lactic acid. Acid. - 2" (c = 5) - 2.3 (c = 20) ( c = 5 ) (c = 5 ) + 3.0 +21-3 - 21.3 - 240 (C = 1.6) (C = 2.7) (in alcohol) + 38.0 Sodium salt. + 13.2" + 20-6 + 16-2 + 59.9 + 13.6 + - 179 + 79.5 Potassium salt.References. +13.7" Purdie and Walker, J. 1895 67 630. + 23-7 Frankland and Apple-yard J. 1893 63, 311. 2268. 1073. +15-5 Stubbs J. 1911 99, +64-4 Landolt Ber. 1873,6, + Wood and Comley J., (ammonium) 1924 125 2639. -+ 75-7 Clough. TABLE 11. The dldecuhr Rotations of the Lower Esters of Some a-Hydroxy-acid-s. Z-Lactates.* [M1:,5" Z-Glycsrates. -f [MI::" d-Ma1ates.t [ M l y d-Tartrates. t [MI:" Z-Hexahydro- [MI?" Z-Mmdelates. [MI:' mandelates. $ d-8-Phenyl-lactates.§ [MF" Methyl. Ethyl. n-Propyl. n-Butyl. + S.6" + 13.4" +17*4" +19*6" $- 5.8 + 12.3 +19.1 +21*4 + 11-1 f 19.3 +25*3 +36-4 + 3.7 + 15.9 +29*7 f27.0 - 36.8 - 24.4 -15.5 -15.4 -276 -233 - -2209 (iso-) + 8.5 + 14.7 - -(at 17") * Wood Such and Scarf J.1923 125 601. t For references see Frank-§ Clough ; land and Gebhard J. 1905,87,865. McKenzie and Barrow J. 1911 99 1021. $ Wood and Comley loc. cit. TABLE 111. The Molecular Rotations of the Amides Methyl ester. Z-lactic acid. + 8.6" Z-Glyceric acid + 5-8 d-Malic acid. + 11-1 d-Tartaric acid. + 3.7 Z-Hexahyhmandelic acid. d-B-Phenyl-lactic acid. + 8.5 - 36.8 (at 30") Z-Mandelic acid. - 276 of Some u-Hydrory-acids. Amide.* + 19.6" (in water) + 66.2 (in methyl alcohol) + 52.8 (in water) + 164 (in water) + 65-4 (in aqueous alcohol) -144 (in water) + 104-2 (in ethyl alcohol) * For referencss see Freudenberg Brauns and Siegel Ber. 1923 56 195. -f McKenzie Martin and Rule J. 1914 105 1599 C O N ~ G ~ ~ ~ O N S OF O P T I C ~ Y ACTIVE COMPOUNDS 2811 From Table IV it is evident that acetylation of the methyl esters of the standard " d "-acids (except that of &tartaric acid) causes the molecular rotations to increase.The introduction of one acetyl group into methyl &-tartrate r a h the molecular rotation, but two acetyl groups in the molecule produce a depression in the molecular rotation. Acetylation of methyl d- p-phenyl-lactate is accompanied by an increase in the molecular rotation but although methyl Z-acetylmandelate possesm a higher spec& rotation (- 146') than methyl 1-mandelate (- 166") the molecular rotation of the former is lower than that of the latter compound. The molecular rotations of the benzoyl derivatives exhibit more irregu-larities; thus the complete benzoylation of methyl Z-lactate of methyl Z-glycerate or of methyl d-tartrate produces decreases in %he molecular rotations but the introduction of one benzoyl group only into ethyl d-tartrate and the benzoylation of methyl d-malab are accompanied by increases in the molecular rotations.The values in Table IV show that an increase in the molecular (or the specific) rotation of methyl d- p-phenyl-lactate is produced on benzoylation and that an increase in specific rotation (but a decreItse in molecular rotation) accompanies benzoylation of methyl Z-mandel-ate. Whilst the data for the benzoyl derivatives do not confirm or refute the conclusions drawn respecting the relative configurations of Z-mandelic and d- p-phenyl-lactic acids the optical rotatory power of methyl Z-phenylmethoxyacetate is in accordance with the view that Z-mandelic acid is a '' d "-a-hydroxy-acid.TABLE IV. TAe Molecular Rotations of the AcetyZ Benzoyl and Methyl Derivatives of Some a-Hydroxy-cacids. Acetyl. Methyl Z-lactate (+ 8.6'). + 76.4" Methyl Z-glycerate ( + 5.8). + 24-6 Methyl d-malate (+ 11-1). + 46.8 Methyl d-tartrate (+3.7). + 16.6 (mono- in water)f - 39.6 (di- in alcohol) Methyl Z-mandelate (-276). - 304 Methyl d-8-phenyl-lactate (+ 8.5). + 16-3 Benzoyl. Methyl. - 35.6" * +112.7O - 87.5 +103.8 + 15-0 + 92-4 - 280 + 180-0 (di- at 100') -382 -173 + 92-2 -(in acetone) 5 * Freudenberg and Rhino Ber. 1924 57 1556. t hudenberg and f McKenzie and Wren J. 1910 Bram Be?. 1922 55 1349. 97 484. It is worthy of note that the effect of a rise of temperature on the optical rotatory powers of the esters of Z-hexahydromandelic acid (Wood and Comley Eoc.cit.) is similar to that on the esters of Z-lactic acid E-glyceric acid d-malic acid d-tartaric mid and 3 Clough. VOL. CXXVII. 5 2812 OPTICAL ROTATORY POWERS AND RELATIVE CONFIGURATIONS. Z-mandelic acid. The influence of organic solvenfs on optical rotatory power will be discussed by the author in a later paper. The regularities observed in the influence of sodium barium and other halides on the optical rotatory powers of a-hydroxy-acids or their esters in solution have also been employed for determining the relative configurations of these optically active compounds. The data in Table V fully confkn the results already obtained. It should be pointed out that other inorganic compounds added to aqueous solutions of the acids in question do not always produce similar alterations in the rotatory powers.For example boric acid produces a diminution in the optical rotatory power of l-(" d "-)lactic acid (Henderson and Prentice J. 1902 81 658), but causes an elevation of that of &-tartaric acid (Biot). TABLE V. The InfEuence of Sodium Bromide on the Optical Rotatory Powers of Some Esters of a-Hydroxy-acids in MetAyE-cdcoholic Solution. In methyl-alcoholic sodium bromide ( N ) . In methyl alcohol. Methyl d-malate. + 8.7' (C = 6 ) - 8.0' (C = 5) Ethyl d - d t e . + 11.6 (C = 6) - 2.4 (C = 5) Methyl d-tartrate. + 4.6 (C = 5) - 8.4 (C = 6) n-Propyl d-tartrate. + 16.0 (C = 6) + 2-6 (C = 6) Methyl Z-mandelate .Ethyl 2-mandelate. -117 (C = 10) -150 (C = 10) Methyl d-p-phenyl-lactate. - 2.4 (C = 2.7) - 16.3 (C = 2.7) -142 (C = 3) -172 (C = 3) Ethyl d-8-phenyl-lactate. + 0.8 (C = 6) - 12.0 (c = 5) That the principle employed in this investigation also leads to correct deductions in other classes of compounds is shown by Karrer's confirmation of the present author's view that Z-asparagine, Laspartic acid and Z-leucine are configuratively related to d-(" Z "-) alanine (Helv. Chim. Acta 1923 6 957; see Part I p. 539). More-over a study of the optical rotatory dispersive powers of a number of corresponding derivatives from the optically active a-amino- and a- hydroxy-propionic acids has revealed regularities from which Freudenberg and Rhino have drawn the conclusion that I-('' d "-) alanine possesses the same configuration as I - ( '' d "-)lactic acid (Ber.1924 57 1551; see Part I p. 548). E X P E R I M E B T A L. l-Mcsndelic Acid-In water (c = 1.59) a s (I = 2) - 5-03', a:; - 5-28" agl - 5-98" a% - 13-55"; [a$& - 158" [a]$,- - 166", [a]& - 188" [a]S8 - 426". In aqueous sodium chloride (4N) (c = 1.59) a& ( I = 2) - 6.45"; [a]i4' - 203". Ethyl l-Mandektte.-+@' 1.128 ; txg3 ( I = 0.5) - 73*04O O L ~ - 76-55", c& - 88*10°; [a]& - 129.4" [a)& - 1357" [a]% - 156.4" THE ACTION OF SIUCA ON ELE-LYTES. PABT n. 2813 In methyl alcohol (c = 10) a& (I = 2) - 23-48" & - 24-38', a?& - 28-20' azs - 65.0"; [a% - 117*4" [ a x - 121*9', [a% - 141*0' [a% - 325". Inmethyl-alcoholic sodium bromide (37) (c = 10.12) a& ( I = 2) - 30.30" a& - 36.55"; [arc - 149*6' [a]& - 180.5".Methyl 1-phenylbenxoyloxymetde prepared by the action of benzoyl chloride on methyl I-mandelate in presence of pyridine boiled at 224-225"/18 111111. e' 1.217; Methyl I-P-phenyl-Ztwiate was prepared by McKenzie and Martin's a:. ( I = 0-5) - 86.05"; [a]$' - 141.4". method (J. 1913 103 117). 1.129; a:* ( I = 1) - 5.35"; [aE* - 4-74'. Methyl d-a-cccetoxy-g-pAenylprope'onccte m. p. 30-31" b. p. 185"/20 mm. was prepared by the action of acetyl chloride on methyl d- P-phenyl-lactate in presence of pyridine. 1.125; a:' (I = 1) + 8.23"; [a];. + 7-33". MethyI l-a-benzoyloxy-p-p~nyl~o~'onde b. p. 224-225'116 mm., was prepared by the action of benzoyl chloride on methyl I-8-phenyl-lactate in presence of pyridine. c* 1.161 ; ar ( I = 1) - 37.65"; The above esters required the correct amounts of sodium hydroxide for complete sapodication which was unaccompanied by change of sign of rotation. Some racemisation may have occurred in the preparation of methyl I-phenylbemoyloxyacetate ; Freudenberg and Markert (loc. cit.) give [a%; - 159.9" for this compound. [a%' - 32.45". The author desires to express his thanks to the Government Grant Committee of the Royal Society for a grant towards the expense of this investigation. ROYAL VETERINARY COLLEGE, LONDON N.W. 1. [Received Ocfober 5th 1925.