STUDIES IN THE PHENYLSUCCINIC SERIES. PART V. 1019 LXXXVIII. -Studies in the Phen ylsuccinic Acid Series. Part V. The Inter-conversion o f the Esters of r- and meso-Diphenylsuccinic Acids. By HENRY WREN and CHARLES JAMES STILL. IN the course of the earlier investigations on the optically inactive diphenylsuocinic acids i t was shown by Reimer (Ber. 1881 14, 1802) that these substances are mutually transformable. When the r-acid is heated with concentrated hydrochloric acid a t 200° the m eso-acid is quantitatively produced whilst the converse trans-formation occurs when meso-diphenylsuccinic acid is subjected to the action of an excess of barium hydroxide solution a t the same temperature. Somewhat later Anschiitz and Bendix (Annulen, 1890 259 91) found that a partial isomerisation takes place when the r-acid is heated with water alone at temperatures between 165O and 200° the meso-acid being formed to the extent of approxi-mately 30 per cent.The transition from the meso- t o the racemic series can be effected however under milder experimental condi-tions when the meso-acid is replaced by its ethyl ester as initial material; thus Anschiitz and Bendix (Zoc. c i t . ) showed that potass-ium r-diphenylsuccinate is the sole product of the action of alco-holic potassium hydroxide solution on ethyl meso-diphenylsuccinate, whilst when aqueous aIcoholic potassium hydroxide is employed a mixture of potassium 7- and meso-diphenylsuccinates is obtained (Wren and Still T. 1915 107 447). The experiments which are now described were undertaken with the hope of more definitely locating the phase a t which the chang 1020 WREN AND STILL STUDIES IN THE i 11 stereochemical configuration occurs.This might conceivably take place before during or subsequent to the actual hydrolysis. Experiments with the di-Z-mentliyl esters of meso- and Z-diphenyl-succinic acids (Wren and Still this vol. p. 531) made it appear probable that the change a t any rate in part precedes the hydro-lysis since it was found that the ester of the Z-acid is converted into that of the meso-acid when heated with aqueous alcoholic potassium hydroxide solution ; under similar conditions the ester of the meso-acid appeared t o suffer isomerisation but the nature of the product could not be definitely established. As these esters are not readily prepared in considerable quantity and as the cli-Z-nienthyl r-ester has not pet been obtained the work has been continued with the more readily accessible methyl and ethyl esters.When ethyl 1.-diphenylsuccinate is hydrolysed with a deficiency of aqueous ethyl-alcoholic potassium hydroxide solution the non-hydrolysed portion is found t o be composed of a mixture of ethyl T- and meso-diphenylsuccinates from which the latter can be readily isolated in the pure state; a similar mixture is formed under like conditioiis from ethyl mesodiphenylsuccinate and from this a pure specimen of the ethyl r-ester can be separated the slightly greater experimental difficulty in this instance being due to tlie relatively greater solubility of the racemic ester.Precisely similar phenomena are observed with aqueous methyl-alcoholic potassium hydroxide solution and the corresponding methyl esters. The pro-ducts of the hydrolysis have not been investigated with respect t o stereochemical configuration since they doubtless consist of mix-tures of potassium salts of the acids and acid estere the approxi-mately quantitative separation of which would be a matter of great difficulty. The experiments just described show that isomerisation a t any rate in part precedes hydrolysis; it may also take place to sGnie extent subsequently since potassium mesodiphenylsuccinate is partly converted into the salt of the r-acid when heated with aqueous-alcoholic potassium hydroxide solution. The change in the reverse direction appears to tak4 place far less readily under similar conditions and could not be definitely proved t o occur.Since i t was thus shown that the esters of the 1.- and meso-acids are interconvertible under the influence of alkali hydroxides it appeared of interest to e,xamine their behaviour in the presence of alkaline reagents under conditions which would preclude hydro-lysis. For this mason a series of experiments has been performed with solutions of sodium methoxide and ethoxide in methyl and ethyl alcohols respectively. The conversion of methyl and ethyl r-diphenylsuccinates into the corresponding m eso-esters can thus b PHENYLSUCCINIC ACID SERIES. PART V. 1021 readily effected ; the latter are considerably less readily soluble in these solvents than the former and the conditions can be so chosen that they separate from the solutions.I n tlhese circumstances iso-merisation proceeds approximately quantitatively. The reverse change can only be effected in much more dilute solution and the isolation of the r-esters involves a series of fractional crystallisa-tions. Lastly the conversion of ethyl 7'- into ethyl meso-diphenylsuccin-ate has been studied under somewhat diff erent conditions. During the last few years it has been frequently necessary to prepare r-di-phenylsuccinic acid and the process adopted has been that previ-ously described by us (T. 1915 107 446 et seq.) which consists in allowing ethyl phenylacetate and iodine to react in ethereal solution in the presence of solid sodium ethoxide and hydrolysing the mix-ture of ethyl r- and meso-diphenylsuccinates which is thus produced.11; has been noticed repeatedly that whilst the yield of r-acid is tolerably constant the proportion of r- to meso-ester produced in the different experiments varies within very wide limits. The ex-planation is now found to lie in tlie observation that ethyl r-di-plienylsuccinate is converted into the nzeso-ester when its ethereal solution is allowed to remain in contact with solid sodium ethoxide. From tlie theoretical point of view the interconversion of the esters in the presence of alkali appears to be most readily explained by the assumption of the formation of a coninion sodio-derivative wliich is decomposed by alcohol according t o tlie sclieme: C0,Et NaOEt t- -+ I PI,-C-H Na*E; Ph-& I Ph-6-H I %z Ph-C-H I E tO 11 C0,Et CO,Et C0,Et C0,Et I I I I H-C-Ph + Ph-C-13 Ph-C-H H -C-Ph I CO,Et h E t E X P E R I M E N T A L .Conversion of Ethyl r-Diphenylsuccinnte i n t o Ethyl mesoDipheny1-s uccina t e. A. By Partial Hydrolysis.-Ethyl r-diphenylsuccinate (0.8 gram) was heated under reflux during two and a-half hours with aqueous ethyl-alcoholic potassium hydroxide solution (0*316N 10 c.c.) ; th 1022 WREN AND STILL STUDIES IN THE solution was poured into water and the mixture extracted with ether. The crystalline residue left after evaporation of the solvent, melted a t 76-114O ; it was repeatedly crystallised from rectified spirit xhereby neiedles of ethyl mesodiphenylsuccinate melting a t 140-141° were readily isolated.B. By the Action of Sodium Ethoxide in Ethyl-alcoholic Solution. -Ethyl r-diphenylsuccinate (1.5 grams) was gently warmed in a small sealed tube with a solution of sodium ethoxide in absolute ethyl alcohol (0*32N 10 c.c.) until an almost clear solution was formed; on cooling the contents of the tube set to a stiff paste, which did not change in appearance wheln preserved for eight days a t the temperature of the laboratory. The solid was filtered washed successively with alcohol water dilute hydrochloric acid water, and alcohol and dried. It weighed 1.4 grams and melted sharply a t 140-141°. The melting point remained unaltered when the substance was crystallised from rectified spirit; it was further iden-tified as ethyl mesodiphenylsuccinate by the mixed melting-point method and by analysis.(Found C = 73.5 ; K = 6.8. Calc. C = 73.6 ; H= 6.8 per cent.) The filtrate from the original crop was diluted with water when a small amount of solid was precipitated which melted indefinitely a t 78-128O. C. B y Solid Sodium Ethoxide.-Finely divided dry sodium ethoxide (prepared from 1 gram of sodium) was allowed t o remain in contact with a solution of ethyl r-diphenylsuccinate (1 gram) in anhydrous ether (20 c.c.) a t the temperature of the laboratory during twenty-four hours. Water was then added whereby two clear solutions were formed; the aqueous portion was once ex-tracted with ether and the ethereal solutions were united and dried over calcium chloride. The residue obtained after removal of the solvent melted a t 75-110° and after being twice crystallised from rectified spirit yielded pure ethyl mesodiphenylsuccinate.The latter melted a t 140-141° and the melting point remained un-changed when i t was mixed with an approximately equal quantity of the synthetic ester. Con u er s ion of E t 11 y 1 me so D i ph e ny lsucci IZ a i e in t o E t h y2 r- Diphenylsuccinate. A. By Partial Hydrolysis.-Ethyl mesodiphenylsuccinate (5.7 grams) was heated under reflux during two hours with aqueous, ethyl-alcoholic potassium hydroxide solution (0*156N 60 c.c.). The resulting solution was evaporated nearly to dryness the residue diluted with water and shaken with a large volume of chloroform. The extract was dried over calcium chloride and the solvent re PHENYLSUCCIINIC ACID SERIES.PART V. 1023 moved. The residue melted a t 76-128O. It was digested with two successive small quantities of boiling light petroleum (b. p. 40-60O). [The part which remained undissolved by this treatment melted a t 133-136O and after being crystallised from alcohol yielded un-changed ethyl iizesodipheriylsuccinate rn. p. 140-141°.] The solu-tions were evaporated to dryness and the united residues extracted with alcohol; the more soluble portion after being crystallised from light petroleum (b. p. 40-60°) yielded ethyl r-diphenylsuccinate. The latter melted a t 83*5-84*5O and the melting point remained unchanged when i t was mixed with the synthetic r-ester. It was also identified by analysis. (Found C = 73.4 ; H = 6.7. Calc., C = 73.6 ; H = 6.8 per cent.) B.By the Action of Sodium Ethoxide in Ethyl-alcoholic Solu-tion.-Finely divided ethyl mesodiphenylsuccinate (5 grams) was shaken with a solution of sodium ethoxide in absolute ethyl alcohol (0*32N 85 c.c.) a t 70° during three hours; at the end of this period, the ester had completely dissolved t o a pale yellow solution which was then poured into a slight excess of dilute hydrochloric acid. The mixture was shaken with chloroform and the extract washed with aqueous sodium carbonate solution and dried over calcium chloride. The residue left after evaporation of the solvent melted at 76-128O. The mixture of normal esters after being treated as described in the preceding paragraph yielded unchanged ethyl mesodiphenyl~uccinate and ethyl r-diphenylsuccinate.The latter melted a t 83-84*5O and no alteration in the melting point was observed when it was mixed with an approximately equal amount of the synt'hetic r-ester. Conversion of Methyl r-Diphenylsuccinate into Methyl mesoDiph en y lsu c cinat e . A. By Partial Hydrolysis.-Aqueous methyl-alcoholic potassium hydroxide solution (0*874N 12 c.c.) was added to a boiling solution of methyl r-diphenylsuccinate (3 grams) in methyl alcohol (200 c.c.) and the mixture heated under reflux during four hours. The alcohol was removed by evaporation and the residue treated with water and a large volume of chloroform. The product obtained after desiccation of the chloroform solution and removal of the solvent melted a t 168-202O. It was twice crystallised from acetone when methyl mesodiphenylsuccinate was isolated in well-defined needles which melted a t 219-220O.No depression of the meltJng point was observed after admixture with the synthetic meso-ester. The substance was further identiiied by analysis. (Found C=72*6; H=6*2. B. By the Action of a Methyl-alcoholic h'olutiom of Sodium Calc. C=72.5; H=6.2 per cent. 1024 WREN AND STILL STUDIES IN THE Methozide.-Methyl r-diphenylsuccinate (1 gram) was suspended in a solution of sodium methoxide in absolute methyl alcohol (0-301N 50 c.c.) and heated a t 50-60° during eleven hours; the ester did not immediately dissolve but after about three hours, the nature of the precipitate was observed to have changed the platelets being replaced by a quantity of very fine needles. After cooling the precipitate was removed well washed with water and crystallised from a considerable bulk of acetone ; well-formed pris-matic crystals of methyl mesodiphenylsuccinate were thus obtained which melted a t 218.5-219*5°.The melting point was unchanged when the substance was mixed with the synthetic mesoester. At the ordinary temperature the change proceeds very slowly, doubtless owing to the comparatively sparing solubility of the r-ester in methyl alcohol. When the ester and alkali solution (approx. 0.25lv) were used in the proportion of 1 gram to 20 c.c., no change appeared to have taken place after nine days; after three months however tho formation of the nzeso-ester could be definitely established. Go I I ilersion of McthyE mesol)ilrT~e?Lyls.zLccinn t e into Me i h y l r-Biphenylsuccinate.A. By 1’urtiul lf yddysis.-Methyl mesodiphenylsuccinate (3 grams) was partly suspended and partly dissolved in boiling methyl alcohol (380 c.c.); 5 C.C. of aqueous methyl-alcoholic potassium hydroxide solution (0.681) were added and the mixture was boiled for an hour. A further portion of the alkali solution (5 c.c.) was then added and the heating was continued for a further period of five hours. At the end of this time the ester had com-pletely passed into solution. The alcohol was removed and the residue shaken with chloroform and water. The mixture of esters obtained lrom the chloroform solution melted a t 158-196O; it was fractionally crystallised from acetone. Unchanged meso-ester was isolated from the less soluble portion whilst methyl r-diphenyl-succinate was obtained by repeated crystallisation of the more soluble part from a considerable bulk of methyl alcohol.The latter was identified by crystalline form melting point (173-174*5O), niixed melting point and analysis. (Found C = 72.3 ; H = 6.1. Calc. C= 72.5 ; H = 6.2 per cent.) B. By t h e Action of a Solutioqz of Sodium Methoxicle in Methyl A IcohoZ.-Finely divided methyl mesodiphenylsuccinate (2 grams) was heated in a stoppered flask during ten hours a t 60° with a solution of sodium (0.9 gram) in absolute methyl alcohol (ZOO c.c.). A small portion remained undissolved. The mixture was exactl PHENYLSUCCINIC ACID SERIES. PART V. 1025 neutralised with dilute hydrochloric acid and the alcohol removed on the water-bath.The residue was treated with warm water and the part which remained undissolved was removed and dried The mixture of normal esters thus obtained melted indefinitely a t 162-182O. It was separated by systematic treatment with acetone and methyl alcohol as described in the preceding paragraph into unchanged methyl mesodiphenylsuccinate and methyl r-diphenyl-succinate the melting points being 218*5-219v50 and 174-175O respectively. A c t i o n of an Excess of h’tltyl-alcoholic Potassiurti Hydroside Solutioii o n r- and meso-Di~henyl.szcccinic Acids. nzesoDiphenylsuccinic acid (1 gram) was heated under reflux with a solution of potassium hydroxide in absolute ethyl alcohol (0*8AT 25 c.c.) during four hours. The substance dissolved slowly, complete solution being ultimately obtained.Excess of alkali was exactly neutralised with hydrochloric acid. The alcohol was removed by evaporation; the residue was dissolved in a small volume of water and treated with a slight excess of a hot solution of barium chloride. On cooling a crystalline precipitate of barium r-diphenylsuccinate separated from which the corresponding acid was isolated; i t melted a t 181-182° resolidified and again melted a t 219-220°. Unchanged mesodiphenylsuccinic acid melting and decomposing at 229-230° was obtained from the filtrate from the crop of barium salt. r-Diphenylsuccinic acid (1 gram) was heated under reflux with ethyl-alcoholic potassium hydroxide solution (O.SiV 25 c.c.). The product was treated exactly as described in the preceding para-graph. Unchanged T-acid was readily isolated from the correspond-ing sparingly soluble barium salt the mother liquors from which, however did not yield rnesodiphenylsuccinic acid in recognisable amount. The authors desire to express their thanks to the Research Fund Committee of the Chemical Society for a grant which has defrayed part of the cost of the investigation. PURE AND APPLIED CHEMISTRY DEPARTMENT, MUNICIPAL TECHNICAL INSTITUTE, BELFAST. [Received October loth 1917.