2698 MORRELL: STUDIES IN THECCLIL-Studies in the Succinic Acid Swies. Part 11.Anilides and Anilic Acids, and t i l e h’fect ofSterG Hindrance o n the Formation of the Arnides.By GEORGE FRANCIS MORRELL.THE method of Bouve’ault and Blanc (Bull. Soc. china., 1905,[iii], 33, 879) for the conversion of acids into the correspondingalcohols by reduction of their esters in alcoholic solution withsodium frequently gives very unsatisfactory results with the di-basic acids of the aliphatic series (compare Harries, A n d e n , 1911,383, 167). The original intention of studying the reduction ofother open-chain derivatives of dibasic acids was hindered by thelack of suitable methods for preparing them in quantity. This isespecially the case with the derivatives of the succinic acids, wherering-formation takes place so readily, and the open-chain deriv-ative forms either a small fraction of the product, or is entirelyabBent.The prment communication deals with an investigation of themethods and conditions requisite for the production of a maximumyield of certain of the open-chain aniline and ammonia derivativesof succinic acid and its homologues.Whilst with substitutedsuccinic acids the neutral anilides were, under all conditions, pro-duced only in traces by the action of aniline on the acids, and theanil wzs generally the sole product, in the case of succinic acidthe aniline could, by repeated treatment of the succinanil obtainedas a by-product, be prepared in excellent yield by this methodunder specified conditions.The formation of the five-memberedring is, therefore, apparently facilitated by the presence of methylsubstituenta in the succinic acid. Where the direct ” methodof preparation failed, good results were obtained by the actionof aniline on the acid chlorides.The anilic acids are of importance on account of their use forthe characterisation of the dibasic acid by Auwers’ method, butthe investigation has here been limited to methylsuccinanilic acid,as the others have already been fully described by other workers.From an unsymmetrically substituted succinic acid, two isomericanilic acids can theoretically be derived, but although methyl-succinanilic acid has been prepared in different ways by manyinvestigators, only one of these possible isomerides has ever beenisolated.Arppe and Biffi (AnmaZen, 1854, 90, 141; 91, 106)obtained an anilic acid, melting a t 14‘i0, from the anil by openingthe ring with alkali. Anschutz (Annulen. 1888, 246, 122; 248SUCCINIC ACID SERIES. PART 11. 2699273) likewise prepared the anilic acid both by Arppe’s methodand by two methods of his own, namely, the reduction of mesacon-anilic acid, and the action of aniline on methylsuccinic anhydride.I n all cases the acid obtained melted a t 143O. Later, Bone andSprankling (T., 1899, 75, 860) give 148-149O as the meltingpoint, and specifically state that they were unable to isolate anyisomeric acid. Auwers (Annalen, 1896, 292, 195) ascribes theformation of only one anilic acid to the influence of the un-symmetric molecule, which thus determines the sense in whichthe aniline is added to the anhydride, or sodium hydroxide tothe anil.Thus, for example, reaction (1) might proceed to theentire exclusion of reaction (2):(1) CH,*YH--UO CH,*QH*CO,HCH,*CO<t CH,*CO*NH*C,H5(3) CH,*YH--CO> + CH,-F]H*CO*NH*C6H,C H,. CO CH,*CO,HIn. support of this idea, he states that in the case of methyl-ethylsuccinic acid, where the lack of symmetry is not so pronounced,two isomeric anilic acids were isolat,ed.I n preparing methylsuccinanilic acid, whether from the anil,or from the anhydride, two points of interest were noted whichseemed t o indicate the incorrectness of Auwers’ and Bone’s assump-tion, and the existence of two isomerides in the product.It wasobserved that the anilic acid was always precipitated as an oil,which solidified slowly on keeping, and that never more thanabout 40 per cent. of the theoretical yield of the acid, meltinga t 149O, could be isolated. Both of these observations w0re quiteat variance with those made in the otherwise perfectly analogouscase of succinanilic acid. It seemed scarcely possible that thepresence of an isomeric acid could have been overlooked by somany investigators, and, indeed, the evaporation of the aqueousmother liquors to dryness yielded only a very soluble, viscidresidue, which, however, was sufficient in amount to account forthe deficient yield. It was not until it Wac discovered that- boththe acids in question were, in aqueous solution, extremely sensitiveto heat, being converted into the above-mentioned viscid products,that an explanation was forthcoming.So quickly does this trans-formation occur tliat the acids cannot even be crystallised un-changed from hot aqueous solution, ax has hitherto been thecustom. On atbempting to recrystallise a quantity of the puresubstance from water, only 40 per cent. was recovered, and, more-over, its melting point was loo lower than when crystallised fromother solvents2700 MORRELT,: STUDIES IN THEBy carefully avoiding anything more than the slightest warmingwhen dealing with aqueous solutions of the acids, the two struc-tural isomerides were satisfactorily isolated. They were purifiedby taking advantage of their different solubilities in water andin chloroform. The less soluble methylsuccinanilic acid melts a t159O, and is the main constituent of Anschutz’s acid (m.p. 143O).Its isomeride is much more soluble both in water and in chloro-form, and melts a t 1 2 3 O . Both acids, on being heated above theirmelting points, lose water, and are converted into methylsuccinanil.No solution has been arrived a t of the problem as to which ofthe acids the constitutionCH3*CH(C?H2*CO2H)*CO.NR.C,H,must be assigned, and to which the alternativeC‘H,*CH (C0,H) *CH,*CO *NH C,H,.The matter is closely dependent on the constitution of the mes-aconanilic acid which, on reduction, yields the methylsuccinanilicacid melting a t 159O (Anschutz, Ber., 1890, 23, 891). Basing hisargument on an erroneous observation of Reissert (Ber., 1888, 21,1370) on the oxidation products of mesaconanilic acid, Anschutzascribed the constitution (I) to this acid, and, c-onsequently, theconstitution (11) to his methylsuccinanilic acid melting at 143O(Annulen, 1888, 246, 117) :C H3*g* CO N H*C,H,C H * C0,HCH,*FH*CO*NH*C,H5C H,* C0,H(1.1 (11.)Neverthelless, after revising Reissert’s work, he convinced him-self that no light whatever could be thrown on the constitutionof mesaconanilic acid, or of methylsuccinanilic acid, as the resultof oxidation expeziments (Ber., 1889, 22, 747; and Annalen, 1889,254, 137).It is noteworthy that during the whole of the controversy overthese anilic acids between Reissert and Anschutz, the melting point,143O, of methylsuccinanilic acid was not challenged by either ofthem, During this present investigation specimens of this sub-stance, crystallised from water, have been obtained, melting a t143--145O, and having all the appearance of individual substances.In the first place, many of Anschiitz’s melting points are some-what low, as has been pointed out by Auwers, owing to the slowmethod of heating which he employed, whereby an incipient d ecomposition of the anilic acid sets in at temperatures below thetrue melting point.Secondly, these anilic acids should not becrystallised from water, for although succinanilic acid &elf seemsto be but little affected, yet others are rapidly attacked. Methyl-succinanilic acid (m. p.159O), for example, has never been obtaineSUCCINIC ACID SERIES. PART 11. 2701after crystallisation from water with a melting point higher thanThe only way open for the preparation of the neutral amidesof succinic acid and its homologues is by the action of ammoniaon the esters. Other methods lead either to the formation of alarge preponderance of the unsymmetrical amide (this Vol., p. 1737)or of the imide. The rate of format4ion of the amides from theesters and the percentage yield obtained has been found to dependon the ester used and on the extent of substitution in the methylenegroups adjacent t o the carboxy!, on spatial influence in otherwords. 'The methyl esters react much more quickly than the ethylesters, although the yield is about the same in each case.Withunsubstituted methylene groups, that is, with succinic ester itself,the reaction proceeds the most rapidly, and the introduction ofmethyl groups produces a marked decrease, not only in the velocityof formation, but also in the yield. The reaction has been carriedout in a number of different ways for the sake of comparison,using the methyl and ethyl esters a t ordinary and a t elevatedtemperatures, and the most satisfactory results have invariablybeen obtained by allowing the met'hyl esters to react a t the ordinarytemperature with concentrated aqueous ammonia,, but insteadof allowing thb liquids to remain in two layers, or using a shakingmachine, just sufficient alcohol was added to bring the ester intosolution. I n the succinic series this method has given betterresults than E.Fischer's process, devised for the malonic series:in which the ethyl esters are heated with alcoholic ammonia ina sealed tube a t 130°, generally for twenty-six hours (Ber., 1902,35, 844). A comparison o t the results obtained in the variousexperiments, combined with Fischer's results in the malonic series,is interesting :14 9-1 50'.Percentage yield ofamide using alcoholicammonia in bomb.7*7Methyl EthylAcid. ester. ester.Malonic ......................... - 98 ............... 40 Methylmalonic -.................. 53 Ethylmalonic -Propylmalonic ................ - 61Dimethylmalonic -Diethylmalonic -Succinic ........................ 63 40Methylsuccinic ............... 33 -.tmrLs-u/3-Dimethylsuccinic .- -ch-aS-Dimethylsuccinic .... -............ 2.6 ............... 0.0__Percentage yield ofamide using aqueousammonia in cold.Methyl ester. Ethyl ester.--80 ( 12 days)-The yield of amide in the case of succinic acid is therefore com-parable with that obtained with metliylmalonic acid, and the sub2702 MORRELL: STUDIES IN THEstitution of one only of the four methylene hydrogen atoms by amethyl group produces a marked retardation in velocity anddiminut'ion in yield. Fischer suggested (Zoc. c i t . ) that the reactionwith tetramethylsuccinic acid would probably yield only a trace ofamide, but it is now evident that this is already the case with thedimethylsuccinic acids, the amides of which have now been preparedfor the first time.These results, whilst quite in harmony withFischer's hypothesis that the methylene hydrogen is involved in thereaction in the formation of a preliminary ammonia additiveproduct, or salt, of the type (111) which decomposes into theCO,Et*CMe:C(OEt).ONH, -+ C02Et.CHMe*CO*NH,(ITI.) PV.1amide (IV), yet show that steric hindrance must be accounted afactor in the case, for there are still in the dimethylsuccinic acidstwo methylene hydrogen atoms similar to the one in methylmalonicacid, yet the velocity of the amideformation and the yield of amideare enormously greater in the latter case, whereas if the presenceof an unsubstituted methylene hydrogen atom were the sole condi-tioning factor we should expect the acids to behave similarly, o r a tleast that more than mere traces of dimethylsuccinamide would beproduced.Moreover, the results with the constitutionally identicalcis- and trcr as-dimethylsuccinic acids are different, the cis- reactingmore slowly than the trans-acid, as one would expect from con-siderations of spatial interference. The conclusion is thereforedrawn that the accumulation of substituent groups round theesterified. carboxyl group hinders the reaction with ammonia, evenalthough some inethylene hydrogen is still unsubstituted.EXPERIMENTAL.Suc cina.nilide.Succinanilide was obtained by Menschutkin (AnnuZen, 1872,162, 187) in 25 per cent, yield by the direct action of aniline onsuccinic acid. It can be obtained in better yield by the actionof succinyl chloride on a solution of aniline in benzene (comparethis vol., p.1736, and Dunlop and Cummer, J . Amer. Clzem. SOC.,1903, 25, 612). Since this method involves the previous prepara-tion of succinyl chloride, which is itself obtained at most in 75 percent. yield, the following direct method of preparation from succinicacid is preferred.Twenty grams of succinic acid were heated f o r three to four hoursat 200° (thermometer in the liquid) with 40 grams of aniline. Avery short reflux air-condenser was used, so that only the anilinewas condensed, tlie water generated by the reaction being alloweSUCCIMIC ACID SERIES. PABT 11. 2793to escape, as it was found that if condensed and returned to theflask the temperature of the boiling mixture eventually sank aslow as 125O, and the unsatdsfactory yield described by Menschutkinwas obtained: The product was poured into dilute acid, and whencold the precipitate of anilide and anil was collected and warmedwith an excess of dilute aqueous sodium hydroxide, whereby theanil was dissolved as sodium succinanilate, but the anilide wasunattacked.The latter was collected, and after one crystallisationfrom alcohol was quite pure. From the aqueous solution of thesuccinanilats dilute hydrochloric acid precipitated succinanilic acidin an almost pur0 condition. The above amount of succinic acidgave 10 grams of anilide and 25 grams of anilic acid, an almosttheoretical yield.Succinanilide crystallises irom alcohol in short, stout needles,melting a t 230^ (Menschutkin gives 227O).It is quite insoluble inwater, and is not acted on by boiling dilute alkali hydroxide. It issoluble in about 35 parts of boiling alcohol, and-460 parts a t 16O,and almost insoluble in the other common organic solvents.Conversion. of Succinanilic Acid into Succinanilide.The anilic acid obtained as a by-product in the above preparationmay be readily converted into the anilide by heating with 75 percent. of ik weight of aniline in sealed tubes at 110-115° for forty-eight hours. The product is a mixture of anilide and anil withexcess of aniline, similar to that obtained in the direct preparation,and the arilide is separated by treatment with hydrochloric acidand then with sodium hydroxide exactly as there described.From25 grams of anilic acid 12 grams of anilide were obtained, and11 grams of anilic acid recovered (compare Tingle and Cram, Amer.Chem. J., 1907, 37, 597, who obtained only a 25 per cent. yieldafter five days' heating in an open vesse'l). By repeat'ing thisprocess with the recovered anilic acid it is eventually almostentirely transformed, giving a total yield of about 30 grams ofsuccinanilide from the 20 grams of succinic acid originally taken.Met hylsuccinanilide.This has been briefly described in a previous paper (this vol.,p. 1736). Unlike succinanilide, i t could be obtained only in tracesby the acti%n of aniline on either the free methylsuccinic acid orits anilic acid. Under all experimental conditions tried, ring-formation ensued with the almost exclusive production of the anil.I n contrast with succinanilide it is very re'adily soluble in alcohol.It is fairly soluble in ethyl acetate, sparingly so in chloroform, andinsoluble in wat.er or benzene2704 MORRELL: STUDlES IK THEMet hylsuccinanil.This was obtained in almost theoretical yield by an improvementof Kling’s process (Ber., 1897, 30, 3040).Ten grams of methyl-succinic acid were gently boiled for a few minutes with 9 gramsof aniline in an inverted retort. The retort was then reversed, andthe mixture distilled as rapidly as possible. No appreciablecarbonisation occurred, and the distillate solidified t o a hard massof the anil, which after one crystallisation from much boiling waterformed clusters of tiny needles melting a t 109-1 loo (Anschutzgives 104O, acd Kling 107O).Methylsuccinanil is very readily soluble in alcohol, ethyl acetate,chloroform, or benzene.It is soluble in about 40 parts of boilingwater, and t,o the extent of 0.28 per cent. in water a t 16O.Methylsuccinanilic Acids.,4n aqueous solution of the sodium salts of the two isomeric acidswas prepared either by dissolving the product of the action ofaniline on methylsuccinic anhydride in cold sodium hydroxidesolution, or rnethylsuccinanil in aqueous sodium hydroxide by theaid of gentle heat. The isolation of the two isomerides was accom-plished by fractional precipitation of the acids from this solution,combined with fractional crystallisation from chloroform.I n oneexperiment 7.7 grams of methylsuccinanil were dissolved in 30 C.C.of 2N-sodium hydroxide, and to the filtered solution hydrochloricacid was slowly added with constant agitation. No oil was precipi-tated, but a clear solution was obtained, from which in a fewmoments crystals of the anilic acid separated. The followingFractions were obtained: (1) After the addition of 20 C.C. of2N-hydrochloric acid 1.9 grams were deposited, melting a t 150°,which, when recrystallised twice from ethyl acetate, melted a t158-159O. (2) On adding a further 10 C.C. of 2147-hydrochloricacid, 2.8 grams were deposited, melting a t 95--135O, which wereextracted with cold chloroform. The residue (1.3 grams) consistedof the acid melting a t 159O, and after crystallisation from ethylacetate melted a t this temperature. The solution contained mainlythe isomeric acid, and it was added to the chloroform solution (seebelow).(3) On keeping overnight, 1.0 gram of material separated,melting a t 85-95O. This was the fairly pure isomeric acid, and wasalmost entirely soluble in cold chloroform.Tho united chloroform solutions were precipitated with lightpetroleum, and the precipitate (m. p. 105-108°) was purified bya process of alternate precipitation from the aqueous solution of itssodium salt, and recrystallisation from chloroform. This procesSUCCINIC ACID SERIES. PART IT. 2705was successful because the difference in the solubility of the iso-merides in water was not so great as in chloroform. Eventually aproduct was obtained melting a t 123O, which consisted of broad,clean-cut, microscopic needles, and further treatment produced noalteration in the melting point.The less soluble acid appeared to form from 40 to 45 per cent.of the total product, but, of course, the more soluble acid couldnever be isolated in a pure condition in quantity anywhereapproaching the amount (55-60 per cent.) in which it waspresent.I n order to remove all doubt as t o the chemical individualityof these two acids, the following data were obtained.Methylsuccinanilic acid, m.p. 159O, crystallises from ethylacetate in fairly broad, flat needles. It is very readily soluble inalcohol, moderately so in ethyl acetate, and very sparingly so inchloroform (about 0-05 per cent.at 18O) or water (0.09 per cent.a t 15.). When heated above its melting point it is converted intothe anil, melting a t logo:0.1011 gave 09361 CO, and 0.0597 H,O.0.1566 ,, 9.2 C.C. N, a t 153 and 749 mm. N=6*85.Methylsuccinanilic acid, m. p. 123O, crystallises from chloroformin clear, broad, microscopic needles. It is extremely readily solublein alcohol or ethyl acetate, very readily so in hot chloroform, anda chloroform solution contains 1.6 per cent. a t 16O. It is fairlyreadily soluble in hot benzene, insoluble in light petroleum, andmoderately soluble in watm (1.2 per cent. a t 15O). When heatedabove its melting point it is converted into the anil melting a t logo.A mixture with the anilic acid melting at 159. melted at 105-108°,and when this mixture was recrystallised fern-like clusters of theusual mixture type were obtained :C = 63.69 ; H = 6.56.CllH13O3N requires C = 63.76 ; H = 6-28 ; N = 6.76 per cent.0.0957 gave 0.2225 CO, and 0.0554 H,O.0.1204 ,, 7.1 C.C.Nz at 16O and 760 mm. N=6*94.C = 63-43 ; H = 6.43.C,,H,,O,N requires C = 63.76 ; H = 6.28 ; N = 6.76 per cent.Succinamide.This compound can be obtained only in minute quantity by theaction of ammonia on succinyl chloride. It was prepared, however,in a variety of ways indicated in the introductory portion, and in80 per cent. yield by the action of concentrated aqueous ammoniaon methyl swcinate, just sufficient alcohol being added to themixture to bring the ester into solution. After three days thereaction was complete, and the precipitated amide was found to b2706 STUDIES IN THE SUCCINIC ACID SERIES.PART 11.almost pure without further treatment. It crystallises from hotwater in short, stout ne’edles, melting and decomposing a t 260O.This is considerably higher than the melting point usually given,and if the temperature rises slowly a much lower value is actuallyobtained. One part of the amide dissolves in 15 parts of boilingwater, and in 300 parts of water a t 1 5 O . It is almost insoluble inalcohol and other organic solvents.Me t h y l s icccinamid e .This was prepared most readily in the same way as succinamideby the action of concentrated aqueous amniaiiia on a solution ofthe methyl ester of the acid. After remaining for five days a t theordinary temperature no more amide was deposited, and the totalyield then amounted t o 52 per cent.of the theoretical. Methyl-succinamide crystallises from water in short needles, melting anddecomposing a t 225O. It is almost insolublt in alcohol and organicsolvents, but soluble in about 50 parts of water a t 15O, and verysoluble in hot water.cis- and trans-Dimethylsuccinamide.[With SIDNEY. HENRY GROENEWOUD.]The only mention of a dimethylsuccinamide in the literature isby E. von Meyer ( J . pr. Chem., 1882, [ii], 26, 359), who states thathe prepared it by the action of ammonia on the oily productobtained by the bromination of cyanethine. The substance isdescribed as crystallising in fine, pyramidal, pointed prisms, whichdid not melt a t 260O. That it could really have possessed theconstitution assigned to it by von Meyer seems impossible sincethese properties agree in no way with those of either the cis- ortrans-amide obtained by a method which admits of no doubt,namely, from the respective esters by the action of ammonia.Itseems, moreover, improbable that the symmetrical amides could beobtiained in any appreciable quantity by the action of ammonia onthe acid bromides, even if such were present in the oil obtainedfrom cyanethine.cis-I)imet~yls-uccinamid.e was obtained by the action of concen-trated aqueous ammonia on dimethyl cis-diniethylsuccinate (b. p.200°), prepared according to Zslinski’s method (Bey., 1889, 22,646), sufficient alcohol being added to make the alcoholic strengthof tho resulting solution about 33 per cent.After being kept forone month a t the ordinary temperature 0.06 gram of amide hadseparated in well-formed, triclinic prisms from a solution containing3 grams of the ester. The mother liquors yielded on evaporatioA RiAGNETIC STUDY OF COMPOUNDS OF WATER, ETC. 2’70’7an oil consisting apparently in the main of unchanged ester, buton treating this a second time with ammonia no less than 0.6 gramof crystals separated in fourteen days. The crystals obtained byboth operations, after washing with alcohol, were quite pure withoutfurther treatment’. They melted and decomposed a t 244O, and werealmost insoluble in alcohol or cold water, but fairly readily solublein hot water:0.0951 gave 16 C.C. N, a t 22O and 767 mm. N=19.49.C,H,,O,N, requires N = 19.44 per cent.trans-Dimeth~lsuccinamide was obtained in a precisely analogousrnanr?er to the cis-amide by substituting the trmas- for the cis-dimethyl esber in the experiment described abcve. Under si iiiilarconditions 3 grams of the trans-ester yielded a larger amount ofamide in the first treatment, namely, 0.15 gram. It was depositedin triclinic prisms of similar appearance, and solubilities in alcoholand water, as the cis-isomeride. It melted and decomposed at 2 3 8 O :0.1098 gave 18.6 C.C. N, a t 20° and 760 mm. N=19*63.C,H,,O,N, requires N = 19-44 p0r cent.Both amides were decomposed extremely slowly by boiling hydro-chloric acid, more rapidly by boiling potassium hydroxide solution.Unfortunately the quantities a t our disposal were too- small for thesaponification products to be satisfactorily identified, but since theesters regenerated their corresponding acids on hydrolysis and itis remotely improbable: that the action of cold ammonia wouldprcduce any change of configuration, it may be confidently assumedthat the amides, also, yield on hydrolysis the respective acids fromwhich they were obtained.THE SIR JOHN CASS TECHNICAL INSTITUTE,LONDON, E.C