161 XVII1.-On y-P~~eizoxy-de?.ivcit~ves of Malonic acid and Acetic acid, and various Compounds used in the Synthesis of these Acids. By WILLJAM HEXRY BEETLEI-, EDWARD HAWORTH, and WILLTAM HEKRY PERKIN, jun. THIS paper contains a description of a number of compounds which were prepared in the course of a research, not yet completed, on the synthesis of methylisopropyltetramethylenedicarboxylic acid, This acid possesses especial interest from the ~H2*~(CH3)*COOH CHz*C( CsH,).COOH' fact that itssformula was f o r a long time considered as the most probable expression of the constitution of camphoric acid. Our idea in attempting to synthesise this acid was to prepare in the first instance a3~~-methylisopropyladipic acid, C 0 OH* C H ( CH,) * C H2.C H2*C H (C,H,) C 0 OH ; to brominate this acid and then to treat the dibromo-acid thus formed with finely divided silver.4: H2G B r ( C H3) C 0 OH CH2* CBr (C3Hi)*COOH In attempting to synthesise az,-rnethylisopropyladipic acid we have met with unexpected difficulties. It was known from the work of Bevan Lean (Trans., 1894,65,997 ; compare also Perkin and Prentice, Trans., 1891, 59, 819, and Guth- zeit and Dressel, Annalen, 1890, 256, 180-188), that, starting with ethylic butanetetracarboxylate, 7 H2*v ( C H3) .C 0 0 H + 2AgBr. CH2.C (C3H7) C 0 0 H + 2Ag= (C 0 OCZH,),CH*CH2* CH2eCH (COO C2Hb) 2, and treating this ethereal salt with sodium ethoxide and methylic iodide, and then agein with sodium ethoxide and isopropylic iodide, it was not possible to obtain ethylic methylisopropylbntane tetra- carboxylate from which the desired acid could easily have been pre- pared, because when this ethereal salt (1 mol.) is treated with sodium (1 atom) and methylic iodide (1 mol.) the dimethyl derivative, is at once produced with regeneration of half of the ethylic butane- tetracarboxylate, so that i t was found necessary, in order to prepare methylisopropyladipic acid, to resort to indirect methods.The following experiments were therefore instituted, and although many of them gave interesting results, we have not been able, so far, in any ( CO 0 CzH,) ZC (C H3) C H2* CH2* C (C H3) (C 0 0 C2H5) 2, TOL. TJX1X-S N162 BENTLEY, HAWORTH, AKD PERKIN : case to obtain sufficient of the methylisopropyladipic acid for analysis and an examination of its properties.(1) The action of sodium etboxide and ethylene dibromide (or chlorobromide) on various mixtures of ethylic methylrnalonate and ethylic isopropylmalonate was studied i n the hope that, in this way, e t.hylic methyl isopropyl bn tanete tracarbox y lat t: might be formed. (COOC2H5)2CNa*CH, + BrCH2*CH2Br + CNa(C,H,)(COOC,H,), = (COOC2~tr,)2C(CR~)*CH,*CH,*C(C,H~) (COOC2HJ2 + 2NaBr. but, at the most, only very small quantities of this ethereal salt could be obtained, and from it no well defined acid could be isolated. ~H2*CH2*~*CH3, w:ts prepared and co 0- (2) Methylbutyrolactone, converted into ethylic y-bs.omethylmet?iyZacetate by treatment with hydrogen bromide and subsequent etherification ; this ethereal salt was then digested with the sodium derivative of ethylic isopropyl- malonate, when it was anticipated that the following decomposition would take place. ( COOC2H6),CNa*C3H7 + BrCH,.CH,*CH ( CHJ)*GOOC2H5 = (C 0 0 CzH,),C (CSH, )*CH,*CH2*CH (CHs) COO C2H6.From this etbylic rnethyliaopropylbutanetricarboxylate, the desired acid could then be obtained by hydrolysis and elimination of 1 mol. of carbon dioxide. Unfortunately, during this reaction, the brom-ethereal salt is evi-. dently for the most part decomposed into methplbutyrolactone and ethylic bromide, so that in this instance again very small quantities only of an ethereal salt of high boiling point were obtained. Some considerable difficulty was experienced in preparing methyl- butyrolactone, and a number of experiments on the action of glycol chlorhydrin on the sodium compounds of ethylic methylmalonate, and ethplic methylacetoacetate, under widely different conditions, failed to give condensation products from which this lactone might readily have been prepared by hydrolysis.Ultimately considerable quantities of methyl butyrolactone were obtained in the following way :- 8-Bromethyl phenyl ether was first prepared by the action of ethylene dibromide on sodium phenoxide in alcoholic solution, CsH5*ONa + BrCHz*CH2Br = CsH,*0.CH2.CH2Br + NaBr, and from this, by digesting it with-the sodium compound of etliylic methylmalonat e, ethyZic yphenoxyethyl-a-methylmalonate was ob- tained. C6H5*O-CE12*CH2Br + NaC(CHJ (COOCzH5)2 = C6H5-0.CH2*CHz*C (CH,) ( cooc2H6)2 + NaBr.7-PHENOXT-DERIVATIVES OF RIALONIC ACID, ETC. 163 This ethereal salt on hydrolysis yields the corresponding acid, which, when heated at NO", loses 1 mol.of carbon dioxide with formation of ~,-p~eenoxyethy7methyZacetic acid, C,H5*O*CH,*CH,*C13(CH,)*COOH; the latter, by the action of fuming hydrobromic acid, is decomposed into phenol and 7-bromethglmethylacetic acid. C,H5*O-CH,*CK,*CH(CH,).COOH + HBr = C6H5*OH + BrCH,*CH,*CH( CH,)*COOH. Roiling with sodium carbonate solution readily decomposes this bromo-acid with formation of methyl Eutyrolactone, BrCH,*CH,.Cj'H*CH, YH,*CH,*qH*CH, + HBr. - - COOH 0-- GO After these experiments had been completed, a paper by R. Marburg appeared in the Berichte (1895, 28, 8 ) describing a different method for preparing m ethylbutyrolactone, which is briefly as follows :- Nthylene dibromide is digested with the sodium derivative of ethylic methylmalonate, when the product of the action is found to contain ethylic y-brometlzylmethylmalonate, CH,Br*CH,Br + NaC(CH~)(COOC,H,), = NaBr + CH2Br*CH2*C (CH,)(COOC,H,),.This etbylic salt, on hydrolysis with barjta water, yields the barium salt of "1- h ydrcxy ethy lmeth ylmalonic acid, CH,(OH)*CH,*C(CHJ (C00)2Ba. The free hydroxy acid is not capable of existence, as, on acidifying its barium salt, it a t once decomposes with elimination of water and formation of a-methylbut,yrolactonecarboxglic acid, H,*CH,*Q (CH,) 43 0 OH, and this on dry distillation yields methylbutyrolactone with evolution of carbon dioxide. The properties of the substance prepared in this way are identical with those of the methglbutyrolactone obtained by us by the method described above.0- co During the course of this investigation many difficulties were encountered which necessitated the preparation and examination of a number of substances which at first sight may appear to have little connection with the synthesis mentioned above. Such of these sub- stances as are mentioned in this cornmnnication may be tabulated for the sake of reference, they are the following:- Glycol phenyl ether, C6H5~O~CH~*CH,~OH. /3-cldorethyl phenyl ether, C6H5*0* CHZ* CH,CI. N BIG4 BENTLEY, HAWORTH, AND PERKIS : p-bromethyl phenyz ether, C6H5*0*CH2*CHzBr. Ethylene diphenyl ether, C6H5*0.CH2*C~2*0.C6H5. Met hy Zene diphen y 1 ether, C6H5*0 c Hz* 0. C6H5, y- Phenox yethy Zmalonic acid, c6H5*O*C H2*CH,*CH(C OOH) :.y-PhenoxyEutyric acid, C6H5*O*CHz.CH2*CH2*COOH. gH2*CH,.pH2 co 0- But yrolactone, Di~henoxyeth~lmalonic acid, (C6HbO*CH2*CHz)zC (COOH),. Diphenoxyeth y lacetic acid, ( C6H50*CH2*CH2),CH* C 0 0 H. P-Pl2enoxyethyl-y-hydi.oxybzLtyric acid, P-Bthozyethyl phenyl ether, c6H5*o*cH2~cH2*o*C2H5. y-Phenoxyethyl-a-methylrnalonic acid, C6H5*O*CH2*CH2*C (CH3) (COOH),. 7- Phenox yet hy 1- a-meth y lacetic acid, f: H2*CH2*yH*CH3 co O-- Met h y 1 but yro Zuc tone, a-~ethyl-y-bromobuty?uic acid, CHT,Br*CHz*CH(CH3)*COOH. A few of the above compounds have been prepared previously, and in these cases we have only given details where we have been able to effect improvements in the preparation. We are still engaged in experiments on the preparation of methyl- isopropyltetramethylenedicarboxylic acid, and hope soon to be able to lay before the Society an account of the results obtained.At the same time we are continuing the examination of some of the substances tabulated above, and especially interesting results are anticipated from the study of the hydrolysis of diphenoxyethylacetic acid. Glycol Monophenyl Ether, C6H5*O*CHz*CH2*OH. To obtain this substance, sodium (1 atom) was dissolved in ethylic alcohol, phenol (1 mol.) and glycol chlorhydrin (1 mol.) added, and the mixture heated in a reflux apparatus until neutral. The alcohol was then distilled off, water added, and the product extracted with ethei-. After washing well, first several times with dilute caustic soda to remove phenol, and afterwards with water, the ethereal solution was evaporated, and the residue distilled under diminished pressure ; the whole distilled between 163" and 166' (80 mm.pressure), the 3-ield being very good. A portion boiling at 165' was collected for analjsip, and gave the following numbers.y-PHESOSY-DERIVATIVES OF Bt ALONIC ACID, ETC. 1 6 5 0.1316 gave 0.0864 H,O an3 0.3358 CO,. This ether is a colourless, thick, oily liquid, insoluble in water, but C = 69.59 ; H = 7.28. C9HlOO2 requires C = 69.56; H = 7.24 per cent. readily soluble in ether or alcohol. / j . ChZorethyZ PhenyZ Ether, C6H5*O*CH2*CHSCl. This has already been obtained by Henry (Bull. Xoc. Chim., 1883, 40, 323) by treating potassium phenoxide with ethylezie chloro- bromide ; in preparing large quantities of this compound we operated as follows.To an alcoholic solution of sodium phenoxide (1 mol.) ethylene chlorobromide (1 mol.) was added, and the mixture heated on the water bath in a reflux apparatus ; sodium bromide immediately began t o separate, and after about two hours boiling the mixture was neutral. The alcohol mas now distilled off, water added, and the product ext'racted with ether ; the ethereal solution, washed with caustic soda to remove phenol, and afterwards with water, was dried over calcium chloride, evaporated, and the residue distilled. The chief portion boiled between 210 and 230°, but there was a considerable residue, which solidified after a time, and consisted of ethylene di- phony1 ether (see p. 166) ; on redistilling the fraction 210-230', it was fomd that it boiled at 220°, and on standing some time nearly the whole of the distillate solidified to a beautiful white, crystalline mass, melting at 28'.0.2501 gave 0.2305 AgCl. C1 = 22.8. CeH90C1 requires C1 = 22.75 per cent. The crystals are very readily soluble in light petroleum, benzene, Henry (Zoc. c d . ) gives the melting and boiling points and alcohol. of this substance at 25' and 221' ( i 5 4 mni.) respectively. /3-BromethyZ PhenyZ Ether, C6H5*0*CH2*CH2Br. This substance is prepared in a manner exactly similar to the chlorinated derivative, using ethylene dibromide in place of ethylene chlorobromide. During the operation, large quantities of vinylic bro- mide, formed from the ethylene dibromide by the removal of hydrogen bromide by the sodium phenoxide, issue from the condenser, and, owing to t'his secondary action, large quantities of unchanged phenol are found in the product ; as this interferes considerably with the fractionation of the product if it is not entirely removed, care must be taken to wash the ethereal solution repeatedly with dilute soda, until it is quite free from phenol. The product is then frac- tionated under diminished pressure, as the bromide decomposes if distilled under the ordinary pressure.The fraction distilling at166 BENTLEY, HAWORTH, AND PERKlN : 140-150' (at 40 mm.) is colle-cted; the residue which solidifies is described later. On redistillation, the bromide boiled almost con- stantly at 144O (at 40 mm.), and gave the following numbers on analysis. 0.2124 gave 0.1991 AgBr. Br = 39.89. p-Bromethyl pheizyl ether is a white, crystalline substance, melting a t 35'.I t possesses in a very high degree the property of superfusion, a pure sample having been kept liquid in a bottle for several weeks ; on removing the stopper the whole solidified with considerable evoln- tion of heat. The yield of bromide obtained by the above method is about 20 per cent. of the theoretical. fi-Bromethyl phenyl ether was first prepared by Weddige ( J . pr. Chenz., 1881, [el, 24, 242), by the action of ethylene bromide on sodium phenoxide, but the details of the preparation and purifica- tion as given by him are troublesome; 8fter many experiments the abope method of procedure was found to be the most convenient. According to Weddige, the ether melts at 39O, and distils at 240-250°, undergoing decomposition and evolving hydrogen bromide.C,H,OBr requires Br = 39.8 per cent. Ethy Zene Diphenyl Zllher, C6H~*0.CH2*CHz*0CGHJ. The residue left after distillation of the /3-brom- (or p-chlor-) ethyl phenyl ether solidifies to an almost colourless crystalline mass, which can be readily crystallised from light petroleum (b. p. 100-120"), in which it is easily soluble on boiling, but admost insoluble in the cold. After repeated recry stallisation, the product melted at 96O, and gave the following numbers on analysis. 0.1402 gave 0.4025 CO, and 0.0828 H,O. C = 78-29. ; H = 6.56. C,,HI4O2 requires c' = 78.5 ; H = 6-54 per cent.. Burr (Zeit. fiir Cheni., 1869,165), who first prepared this substance, gives the melting point as 98*5O, whereas Lipmann (Zeit.fur Ohem., 1869, 447) states that it melts at 95O. Action of Methylene Chloride and Nethylene Iodide on Sodium Phen- oxide. dfethyzene Dipphenyl Ether, C6H6*O*CH$O*C6HS. These experiments were instituted in the %ope of obtaining chloro- methyl phenyl ether and iodomethyl phenyl ether, substances which were required for a series of synthetical experiments, Methylene iodide, C HJ2, and methylene chloride, CH,Clz, were treated with sodium phenoxide, in proportions theoretically required to form C6H5*O*CH~I and C6H,*O*CH2C1. I n the former case, thery-PHENOXT-DERIVATIVES OF MALONIC ACID, ETC. 167 mixture was heated on the water bath in a reflux apparatus, but when the chloride was used the mixture was heated i n soda-water bottles in boiling water for five hours ; the product was isolated exactly as described in the case of the preparation of /3-hromethyl phenyl ether from ethylene dibromide.I n the present case, however, the sodium phenoxide, curiously enough, acts on one half of the iodide or chloride only, and leaves the other half unchanged ; methylene diphenyl ether being the sole product of the action. This compound is a colour- less, syrupy liquid boiling at 205O, under a pressure of 50 mm. When cooled to Oo i t solidifies to a colourless, cryst(a1line mass, which melts at about 15'. The following numbers were obtained on analysis. 0.1187 gave 0-3377 CO, and 0.0715 H20. C = 77.59; H = 6.69. 0.1523 ,, 0.4334 ,, ,, 0.0810 ,, C = i7.61; H = 5.91, C,,H,,O, requires c! = 78.00 ; R = 6.00 per cent. Attempt.8 were subsequently made to obtain C6H,*O*CH2Br from the compound just described by treating it with hydrogen bromide under various coiiditions, but in t'his we were unsuccessful, as, even when we used the theoretical quantity of hydrogen bromide dissolved in acetic acid, one-half was converted into methylene dibromide and the otlier half remained unchanged. Methylene diphenyl ether has been described by Henry (Ann.Chim. Phys., 1883, [ 5 ] , 30, 269) and by Arnhold (Annulen, 1887, 240, 201) as a liquid boiling at 293-296O. yPhenoxyethy ZmaZonic acid, C6H,0*CH2*CH2*CH( COOH),. This substance is easily prepared as follows :-Ethylic malonate (13 grams) is added to sodium (2 grams) dissolved in alcohol (25 gramP), and the mixture treated with p-bromethyl phenyl ether (14 grams).The whole is then heated on the water bath i n a. reflux apparatus till neutral, after which it is cooled, diluted with water, and the oil which separates extracted with ether ; the ether is evaporated, and the light yellow, oily residue hydrolysed by boiling with alcoholic potash (14 grams) for two hours. The alkaline soh- t,ion is evaporated with water until all the alcohol has been expelled, and is then acidified and extracted with ether; the ethereal solation is dried over calcium chloride, the ether boiled off, and the resulting oil poured into a basin when it quickly solidifies. Finally the sub- stance is puri6ed by cryatallisation from xylene from which it separates in minute needles melting at about 142" with slight evolu- tion of gas. Analyses.0.1168 gave 0.2520 CO, and 0.0586 H20. C = 58-89 ; H = 5.39. CsHaO*CH,~CH,*CH(COOH), requires C = 58.93 j H = 5-35.168 BENTLEE', HAWORTH, AND PERKiN : ~ - P h e ~ z o s ~ e t h y l ~ z a l o n i c acid is sparingly soluble in cold, readily in hot water; i t is very sparingly soluble in benzene, and almost in- solnble in light, petroleum, but it dissolves very easily in alcohol and ethylic acetate, and is fairly soluble in ether. yPhenoxybutyric acid (y-Phenoxyethylac~tic acid), CGHsO.CH2.C Hz* CH z*C 0 0 H. This acid was readily obtained on heating yphenoxyethylmalonic acid a t 150--160° until the rapid evolution of carbon dioxide had slackened, and then finally raising the temperature to 200' for a few minutes ; the residual syrup, which was of a pale brownish colour, solidified to a hard mass on cooling.It was easily purified by re- crystallisation from light petroleum (b. p. 100-120'), from which i t separates in thin plates melting a t 64-65'. 0.1346 gave 0.3282 C02 and 0.0808 H,O. C6H50~CB2*CH,*CH2*COOH requires C = 66.66 ; H = 6.66 per cent. yPlzenoxpbutyiic acid is sparingly soluble in cold water, easily iii hot, and, on cooling, separates in the flocculent condition. It is easily soluble in benzene, ethylic acetate, alcohol, and acetic acid. C = 66.50; H = 6-67. f: Hz* C H2* Q ET2 O-- co ' Butyolactone, A number of experiments were conducted with the object of dis- covering the best possible means of replacing the phenoxy-group in yphenoxybutyric acid by the hydroxy-group ; in this case the y-hy- droxybutyric acid formed would imniedizttely lose water, yielding butyrolnctone. yPhenoxybu tyric acid (25 grams) was gently heated on the water bath with fuming hydrobroniic acid (60 c.c.) i n zt reflus apparatus for about eight hours, and afterwards for the same length of time on the sand bath.On cooling acd diluting with water, a heavy black oil separated which was extracted with pure ether, and the ethereal solution mashed with water. The ethereal solution was then extracted eeveral times with a strong solution of sodium carbonate, the extracts boiled with animal charcoal for 12 hours, and the liquid filtered from the animal charcoal ; the pink filtrate, after being evaporated to a small bulk, was extracted with ether to remove phenol, and then acidified and again extracted repeatedly with pure ether.This ethereal solution was dried over calcium chloride, the ether removed by evaporation, and the residual oil (about 5 grams) fractionated. Practically the whole of the oil distilled between 20k0 and 206' at the atmospheric pressure, and a sample oE the oil boiling a t 205' yielded the following results on ttnalysis. The following method gave the best results.y-PHE~OBf-DERIVBTIVES OF MALOSIC ACID, ETC. 169 0.1020 gave 0.2090 CO, and 0.0646 H20. C = 55.88 ; H = 7.03. C1H60, requires C = 55-81 ; H = 6.97 per cent. The substance lva 8 : there fore, evidently y-butyrolactone, which, according to Fittig and Rocder (Annden, 1885, 227, 22), boils a t 206'. Diphenoxyeth yhzalonic acid, ( C6H50*CH,.CH,),C(COOH),. This acid has been prepared in considerable quantities ; the method me usunlly employed being as follows :-Ethylic malonato (16 grams) is added to sodium (2.3 grams), dissolved in alcohol (30 grams), and the mixture heated with fi-brornethjl phenyl ether (20 grams) on the water bath till neutral; the product is then cooled and again treated with sodiuni (2.3 grams), dissolved in alcohol (30 grams), and p-bromethyl phenyl ether (20 grams), and the mixture once more heated on the water bath till neutral.On adding water, a heavy oil separates; this is extracted with ether, thc ether removed by eva- poration, and the oily residue hydrolysed by boiling with alcoholic potash (17 grams). After removing the alcohol by evaporation with water, the solution is acidified, and the copious white precipitate of crude diphenoxyethylmalonic acid thus produced is collected, washed with water, and dried 011 a porous plate until quite free from oily impurity.It is then purified by recrystallisation from 50 per cent. acetic acid from which it separates in rhombic prisms melting and decomposing a t 150". 0.1266 gave 03098 CO, and 0.6680 H,O. (C6H50*CH2*CH2)2C(COOH), requires C = 66.28 ; H = 5.81 per cent. ~~1ie~zoxyet,72ylmal~~zic acid is nlmost insoluble in cold water, very slightly soluble in hot water or benzene, and almost insolnble in light petroleum; it is moderately soluble in ether, ethylic acetate, and alcohol, aud is extremely soluble in acetic acid. It is reprecipitated by water from its alcoholic and acetic acid solutions. C = 66.44 ; H = 5.96.Diphenoxyethylacetic acid, (C,H,O~CH,*CH,),CH~COOH. This compound was prepared by heating dipheiioxyetbylmalonic acid a t lFOo until carbon dioxide ceased t o be evolved; the brown, syrupy residue solidified completely on cooling, and was readily puri- fied by recrystallisation from light petroleum (b. p. 100-120"), from wvEich it separated in feathery groups, melting a t 88". 0.1054 gave 0.2788 CO, and 0.0625 H,O. (CsH50~CH2~CH2)2C€€~COOH requires C: = 72-00 ; H = 6.66 per cent. D~lzeizoxyethylacetic mid is insoluble in cold, and only sparingly soluble in hot, water ; it is sparingly soluble in cold, light petroleum, C = 72.14; H = 6.59.170 BENTLET, HAWORTH, AND PERKIN : easily in the hot liquid, and very soluble in benzene, ethylic acetate, alcohol, and acetic acid ; its alcoholic and acetic acid solutions yield flocculent precipitates when diluted with water. P-P henox yet hy I- r-ph ydr0s.y butyric ucz'd, OH'' H2* cH2> C H*C 0 0 H.CsH,O*CH,*C H, This substance was obtained accidentally in examining the product formed by heating a sample of crude diphenoxyethylacetic acid in a sealed tube with a solution of hydrogen chloride in acetic acid for some hours at about 130' ; the contents of the tube were diluted with water, and the dark, heavy oil which was precipitated was extracted with ether, the ethereal solution washed repeatedly with water to remove acetic acid, and the ether evaporated. The dark, oily residue was then boiled with a strong solution of sodium carbonate for it considerable length of time, in order to remove chlorine.The alkaline solution was now extracted with ether, to remove phenol, acidified, extracted with ether, and the ethereal solution dried with calcium chloride and filtered ; shortly afterwards it was observed that crystals were separating from the ethereal solution ; these were collected, washed with ether, dried on a porous plate, and recrystal- lised twice from benzene, in which i t dissolves but slightly. I t crptallises in prisms, which melt at 1 1 2 O , but sinter several degrees below this temperature. 0*1083 gave 0.2578 CO, and 0.0716 H,O. C = 64.92 ; H = 7-33. When pure, this substance is almost insoluble in ether, very sparingly soluble in light petroleum, but moderately easily in water. The siher salt, CI2Hl5AgO4, was prepared by precipitating an aqueous solution of the ammonium salt with silver nitrate; it is moderately soluble in hot water, and ci*ystallises on cooling in white tufts.0.1092 gave 0*0358 Ag. Ag = 32.78. C,,H,5AgOa requires Ag = 32.63 per cent. With copper sulphate solution, the aqueous solution of the ammo- nium salt gives a bluish-white precipitate, which dissolves on boiling, and separates out again on cooling, apparently not in the crystalline condition. Lead acetate solution gives 110 precipitate at, first, but, on standing, a white, crystalline salt gradually separates ; this redissolves on boiling, and crystallises out again on cooling. Barium nitrate and calcium chloride give no precipitate with the aqueous solution of the ammonium salt.ry-PHENOST-DERIVATIVES OF MALONIC ACID, ETO.171 Action of /3-Bronzethyl Phenyl Ether on the Sodium Derivatire of Et h y 1 ic Meth y lrnalon ate. Ethylic -pPhenoxyethyl-a-Nethylrnaloiiate, CCH5O*CH2.CHz.C (CH,) (COOCzH5),. This substance is obtained when the bromo- or chloro-ether, C6H~*O*CB2.CH2Br or C,H5*O*CH,*CH2Cl (1 mol.), reacts with the sodium derivative of ethylic methylmalonate (1 mol.) in alcoholic solution. I n the case of the chloride, the action proceeds slowly, six hours boiling being required to complete it, but in the case of the bromide, it sets in on gently warming, and is so vigorous as to main- tain the mixture a t the boiling point for some time ; when the decom- position is complete, wateris added, and the oily product is extracted with ether. The ethereal solution is washed with water, dried over calcium chloride, evaporated, and the residual oil fractionated under reduced pressure, when the bulk of it distils at 230' (45 mm.) as a colourless, thick oil, which, on analysis, gave the following numbers.C = 65.01 ; H = 7-39, C,,H,,06 requires C = 65.3; H = 7.M per cent. 0.1392 gave 0.0927 HzO and 0.3318 CO,. Ethglic y-phenoxyetltyl-a-methylinalonate is a colourless syrup, which, even on long standing, showed no signs of crystallising. During the fractionation of the crude product of the action of pben- oxyethylbromide on ethylic sodiomethylmalonate, a considerable quan- tity of an oil of low boiling point was obtained, which, on subsequent fractionation under the ordinary pressure, was found to contain, besides ethylic methylmalonate, a liquid free from halogen, and boiling a t about 230".In order to free this substance from ethylic methyl- malonate, i t was boiled with excess of alcoholic potash for four or five hours, when a large quantity remained uiisaponitied. Water was added, the oil which was precipitated extracted with ether, the ethereal solution well washed with wat,er, dried, and evaporated. The oily residue thus obtained, when distilled, boiled constantly a t 2YOo under the ordinary pressure. The analytical results agreed w i t h the formula C6H50*CH2*C H,*OC,H5. 0.1502 gave 0.1150 H20 and 0.3974 CO,. /3- Ethoxyethyl phenyE ether is a colourless, mobile oil of penetrating C = 7215; H = 8.50. C,oH,kOz requires C = 72.28 ; H = 8.43 per cent. odour, resembling that of benzyl ethyl ether, C6H5*CHz*OCaH5.yPhenoxyethy1-a-methylmalolzic acid, C~HJO*CH~*CH,.C(CH,) (COOH),. I n order t o prepare t h i s acid, ethylic yphenoxjethyl-a-methyl malonate (50 grams) was boiled with alcoholic potash (50 grams).178 BYSTLEY, HAWORTH, AND PERK1:T : There appeared to be very little action in the cold, but, on gently warming, a large quantity OE an insoluble potassium salt soon sepa- rated ; sufficient water mas added to dissolve nearly the whole of this, and the mixture boiled on the water bath in a refliix apparatus for two or three hours. Water was tlhen added, the alcoliol completely rcmoved by evapomtion on the water bath, the residue dissolved in water, cooled, and acidified with hydrochloric acid ; the crude ~,-phenoxjethyl-a-rnethylmalonic acid, which then separated as a thick, heavy, brown oil, was extracted with pure ether, and the et.herea1 solntion dried over calcium chloride and evaporated.After standing overnight in a vacuum over sulphuric acid, the oil solidified to a, bard crystalline mass, which was readily purified by recrystalii- sation from hot benzene. The followingare the results of the analysis of this substance. 0.1312 gave 010684 HzO and 0.2920 COz. C,,B,,05 requires C = 60.50 ; H = 5.88 per cent. .I-Phenoxyethyl-2-methylmnlonic acid crystallises in colourless prisms which melt a t 125O with decomposition and formation of yphenoxy- cthyl-x-met hylacetic acid and carbon dioxide. It is sparingly soluble in cold water or cold benzene, aiid insoluble in light petroleum, but readiiy soluble in hot water, hot benzene, alcohol, or ether.C = 60.69; H = 5-79. ?~-YhenoxyethyE-x-?izethyZacetic acid, C6H50*CH2*CH2*C H (C H3) *C OOH. This Rubstance was prepared by heating yphenoxyethyl-a-methyl- malonic acid a t 180" until evolution of carbon dioxide had entirely ceased, and then distilling the residual oil under diminished pressure. The whole distilled between 205' and 210' (45 mm.), the correct boil- ing point a t this pressure being 207'. A small portion of the distil- late, which, 011 cooling, soliditied immediately, was recrjstallised from light putroleurn (60-goo), and thus obtained in the form of small, colourless crystals melting a t 80". C = 67.91 ; H = 7-00, 0.1745 gave 0.1100 H,O and 0.4345 GO,. CllHIIOYrequires C = 68.04; H = 7.21 per cent. This acid is readily soluble in alcohol, ether, or benzene, mode- rately so in hot water and light petroleum, but only sparingly in the two last-named solvents in the cold.Silver salt, C6H,0~CHz~CHz~CH(CH,).COOAg.-~~~s was pre- pared by suspending t'he acid i n water and gradually adding ammonia until the whole had dissolved; the solution was then boiled t o get rid of the slight excess of ammonia, and silver nitrate added when the solution was cold. The white, flocculent precipitate thus ob- tained was collected, washed well with water, spread on a porous plate, and dried in a vacuum over snlphuric acid.7-PHENOXT-DERIVATIVES OF MALOXIC ACID, ETC. I 7 3 0.0910 gave 0.0382 H,O and 0.1456 CO,. 0.1298 ,, 0.0467 Ag. Ag = 35.98. This silver salt is somewhat soluble in boiling water, and separates again, in the amorphous condition, on cooling. A neutral solution of t!;e ammonium salt of PI-phenoxyethyl-a-methylacetic acid gives no precipitate with barium or calcium salts, but, on adding lead acetnte, a white, amorphous precipitate is thrown down, which is somewhat soluble in boiling water.With copper salphate a flocculent green precipitate is obtained insoluble in boiling water. C = 43.65; H = 4 66. C,,H,,O,Ag requires C = 43.85 ; H = 4.32; Ag = 335.88 per cent. Action of Brornethyl Phenyl EtJier on E t h y l i c NetJLylncetoncetate. This reaction was carried out as follows. Sodium (4 grams) was dissolved in ethylic alcohol (50 grams), the solution cooled, and a, mixture of ethjlic methylacetoacetate (25 grams) and bromethyl phenyl ether (35 grams) added.In the cold there appeared to be no action, but, on heating on the water bath in a reflux apparatus, sodium bromide quickly separated ; the mixture, which, after boiling for about two hours mas neutral, was poured into water, and the oily prodncts extracted with ether in the usual way. On distilling the dry product under a pressure of 40 mrn. ethylic methylacetoacetate first passed over; the thermometer then rose rapidly, and at 1@5O almost the whole of the new compound distilled. CsH,0*[ICH2],*C(CH~)(CO*CH,).COOC,B, requires C = 68.10 ; H =1 7-55 per cent. Ethylic -,-phenoxyethyl-a-methylacetoacetate is a thick, colonrless oil which, on hydrolysis with strong alcoholic potash, yields rpphen- oxyethyl-a-metbylacetic acid.0.140c) gave 0.0983 H20 and 0.3473 CO,. C = 67-64! ; H = 7.80. Formation of a-Methylbutyrolactone fvow r~-Phenoxyethyl-a-rnethylacetic acid. yPhenoxyethyi-a-methylacetic acid is moderately easily decom- posed by heating with mineral acids with formation of a-melhyl- butyrolactone ; the best results being obtained as follows. The pure acid is heated in sealed tubes with a strong solution of hJdrogen bro- mide in glacial acetic acid for six hours at 100" ; the contents of the tubes are then diluted with water, the products extracted with ether, and after the ethereal extmct has been washed with water until free from acetic acid, the ether is distilled off, and the residue is boiled with potassium carbonate solution for 12 hours. The phenol formed is then removed by means of ether, the aqueous solution concentrated on the water bath, and, afber cooling, acidified and boiled in a reflux174 v-PHENOXY-DERIVATIVES OF MALONIC ACID, ETC.appamtus for two hours, to convert the hydroxy-acid into the lactone. The solution is then repeatedly extracted with pure ether, the ethereal solution dried over calcium chloride, evaporated, and the product distilled. In this way, a colourless, mobile liquid is obtained which boils constantly at 2Olo, and is evidently identical with the a-methylbu tyrolnctone described by Marbnrg (Ber., 1895, 28, 10). a- Meth y I- y -2lromohutyric acid. In order to prepare this substance, pure a-methylbuyrolactone is left for 24 hours at the ordinary temperature in contact with satn- rated aqueous hydrobromic acid ; the product is poured into water, all rise of temperature being carefully avoided, and the liquid rapidly extracted with ether.After washing well with water, the ethereal solution is dried and evaporated, when a brown, oily residue is left, which cannot be purified by distillation, as it decomposes readily on warming; for analysis i t was, therefore, merely Jeft over sulphuric acid in a vacuum for a, short time. 0.2732 gave 0.2840 AgBr. This acid gives off hydrogen bromide: at ordinary temperatures, Br = 44.04. CsH9Br02 requires Br = 44-19 per cent. very probably with formation of a-methylbutyrolactone. Ethylic yBrom-a-methy Zhutyrate, CH2Br*CH2*CH(CH3) *C 00C2H6.- The impure ~-brom-a-metl~ylbutyric acid obtained as described above was dissolved in ethylic alcohol and the solution saturated with dry hydrogen chloride ; after 24 hours, water was added, the ethereal salt extracted with ether, and the ethereal solution, after being well washed with water and sodium carbonate solution, was dried over calcium chloride, and evaporated. I n this case also, the oily residue could not be distilled, for although it did not give off hydrogen bromide so readily in the cold as the acid did, it decomposed rapidly below its boiling point.After standing in a vacuum over sulphuric acid for 12 hours, the bromine was determined. 0.2460 gave 0.2146 AgBr. Br = 37.12. C,H,02Br requires Br = 38-27 per cent. Action of Phosphorus Pentachloride on a-ll.lethyIhutyrolactone. In order to study this decomposition, phosphorus pentachloride (20 grams) was gradually added to a-methylbutyrolactone (10 grams), the mixture being well cooled with water during the addi- tion. When all the pentachloride had been added, and the wholeHAWORTH AND PERKIN: THE PREPARATION OF GLYCOL. 175 allowed to stand for one hour, the action was completed by heating for one hour on the water bath. On subsequently distilling the pro- duct, phosphorus oxychloride passed over first., and then the tempera- ture rose to 1 8 9 O , at which the rest distilled; there was, however, some decomposition accompanied by charring and evolution of hydro- gen chloride. The analysis of the product obtained in this way did not give very good analytical results, although they indicated that the substance was ~-chlor-a-met7~lllbutyryl chloride, CHzC1.C H2*CH (CH,)*COCl; this was borne out by the study of the properties of the chloride. Anilide of ly-Chlor-a-rnethy Ibutyric acid, C HZC1.C H2.C H (CH,) *C 0 *NH*CCHs. This crystalline substance is obtained when tbe product of the action of phosphorus pentachloride on a-methylbutyrolactone is slowly poured into aniline, the mixture being well cooled during the addition. After standing for one hour, the product is poured into water, dilute hydrochloric acid added until the excess of aniline has been removed, and the whole extracted with ether. The ethereal solution, after being washed successively with dilute hydrochloric acid and with water, is evaporated, and the residue left in a vacuum over sulphuric acid until it gradually deposits crystals. These are freed from oily mother liquor on a porous plate, and then recrystallised from light petroleum (b. p. 100-120"). The beautiful white prisms thus obtained melt a t 106'. N = 6-96, 0.1155 gave 7.0 C.C. moist nitrogen at 18' and 753 mm. C11H140ClN requires N = 6.62 per cent. Owens College, Manchester.