THE ESTERIFICATICJN OF 3-NITROPHTHALIC ACID. 1135 CXXL-The Esterification of %Niti*ophthalic Acidd By ALEX. MCKENZIE, Grocers’ Company Research Scholar. VICTOE MEYER’S rule for the ester formation of aromatic acids is of such general applicability that exceptions to it present certain points of interest. Such an exception is 3-nitrophthalic acid. Faust (Annulen, 1871, 160, 56) obtained a crystalline ethyl hydrogen ester by con- ducting the esterification in the cold, whilst a normal ester resulted as an oil on rise of temperature, Since, however, the product of the nitration of phthalic acid has been shown by 0. Miller to be a mixture of 3- and 4-nitrophthalic acidf, and is not homogeneous as Faust apparently supposed, mucn weight could not be attached to the observation of the latter investigator.The different behaviour of the isomeric nitro- phthalic acids on esterification by the hydrogen chloride method mas noted by Miller (Bey., 1878, 11, 1191 ; Anncden, lSS1, 208, 227), who points out that when the mixture resulting from the nitration of phthalic acid is directly esterified, the 4-nitrophthalic acid is converted into the normal ester, the 3-nitrophthalic acid, on the other hand, slightly into the normal ester, and mainly into the acid ester. V. Meyer and Sudborough (Ber.s 1894, 27, 3151) suggested that the presence of this normal ester might possibly be attributed to the prolonged action of the methyl alcohol and mineral acid causing slight decomposition of the 3-nitrophthalic acid into mononitrobenzoic acid, the melting point of the methyl ester of which agrees closely with that observed by Miller for the normal ester, Wegscheider and Lipschitz (Monatsh., 1900, 21, 787) have supplied experimental evidence for the invalidity of this hypothesis by hydrolysing the normal methyl ester produced on the esterification of 3-nitrophthalic acid by the sulphuric acid method, and by identifying the resulting compound as 3-nitro- phthalic acid.With regard to the explanations adduced to account for the devia- tions from the V. Meyer rule, Graebc’s observation that tetrachloro- phthalic acid formed an ethyl hydrogen ester when esterified by the hydrogen chloride method (AnnuZen, 1887, 238, 327), was attributed by V. Meyer and Sudborough (Zoo. cit.) to the probable existence of tautomeric forms, the acid esters of substituted phthalic acids being represented, €or instance, as C6HI<g$E and C6H4<:>0.Similarly, Graebe (Ber., 1900,33,2027) supposes that in the esterifica- tion of 3 : 6-dichlorobenzoylbenzoic acid, which is also an exception to the V. Meyer rule, the acid acts as the tautomeric oxyphthalide, thus ; RO OH \/ 4 H 21136 McKENZIE : THE ESTERIFICATION OF /C( OH)*C,H, c6c12\ >O + C2H5*OH = CO V. Meyer, as well as Wegscheider, assumes that the anhydride is the intermediate product, and that this is further acted on by the alcohol; for example, the acid ester of 3 : 6-dichlorophthalic acid (Graebe, Ber., 1900, 33, 2019) results according to the scheme : and when attempts are made to convert it into the normal ester, its comportment accords with the V.Meyer rule. Marckwald and the author (Ber., 1901, 34, 485) have recently separated the alcohols of fuse1 oil by converting them into the crystal- line P-acid esters of 3-nitrophthalic acid. Inactive 1-isoamyl-3-nitro- phthalic acid aud 1-d-amyl-3-nitrophthalic acid mere isolated, and the corresponding alcohols, isobutylcarbinol, (CH,),CH*CH2* CH,*OH, and I-methylethylcarbincarbinol, CH,*(C2H5)CH*CH2*OH, were ob- tained from them on hydrolysis. We noticed, in the course of the work, that (1) when 3-nitrophthalic acid was esterified by amyl alcohol by E. Fischer and Speier's method, the main product was the P-acid ester, but the a-acid ester and the normal ester were also formed, (2) when the alcohol was directly esterified by 3-nitrophthalic anhy- dride, the main product was the a-acid ester, the P-acid ester being also present.Wegscheider and Lipschitz (Zoc. cit.) have shown that when the acid is esterified in presence of sulphuric acid and methyl alcohol, the main product is the P-acid ester, but the normal ester is also produced under certain conditions. Direct esterification by the anhydride, on the other hand, was found by them to yield 90 per cent. of the a-compound. Isomeric acid esters of the type under consideration vary in electrical conductivity, and Wegscheider has shown this in several cases, for example, NO2 a-Ester ( K = 0 -2). NO, \/CO,CH, ()CO,H &Ester ( ~ = 1 ' 5 ) . In fact, Wegscheider bases his nomenclature of such compounds on the difference in conductivity, that ester with the smaller value for K being termed the a-ester (Monat~h., 1895, 16, 141, &c.).Of the two carboxyl groups in 3-nitrophthalic acid, the one in the ortho-position3-NITROPHTJTALIC ACID. 1137 relatively to the nitro-group is the ‘Lstronger ” of the two, and the stereochemical obstruction caused by it is more marked than that, caused by the other group in the 1-position, Therefore on esterification by the hydrogen chloride or sulphuric acid method, the P-acid ester is the main product. According to this view, both isomerides might be ex- pected to be formed, the relative amounts of which would depend on the difference between the carboxyl groups in the particular acid used. The present paper affords evidence for the formation of both isomerides on the esterification of an unsymmetrical dicarboxylic acid, a probability which has been repeated1.y suggested by Wegscheider (Monatsh., 1895, 16, 141 ; 1897, 18, 640 ; 1899, 20, 696 ; Oesterr.Chem. Zeit., 1901, 6 ; Ber., 1901, 34, 650). The formation of the normal ester on esterifi- cation by the sulphuric acid method was. also observed. Further, inactive 2-isoamyl-3-nitrophthalic acid and 2-d-amyl-3-nitrophthalic acid have been prepared and examined. For the preparation of 3-nitrophthalic acid, the method by nitration of phthalic acid (Miller, Annulen, 1881, 208, 225) is most convenient. On nitrating, care should be taken to observe just when the action begins, and at once to moderate i t by cooling, otherwise it proceeds too violently. The melting point of the acid used in the following experi- ments agreed with that of Miller.3-Niti*ophthaZic Anhydvide. The following was found a suitable means of preparation. Equal weights of the acid and acetic anhydride are gently heated with the free flame until all the acid dissolves, and then for five minutes longer to complete the reaction. When the solution cools, the anhydride quickly crystallises, and is drained off and washed with ether. It melts at 162’. A further quantity may be obtained from the mother liquor on removal of the ether and the bulk of the acetic anhydride. The method gives an almost theoretical yield. 2 -is0 Amy I-3-nitrophthab ic Acid. The corresponding P-acid ester, which yielded isobutylcarbinol, has already been described (Marckwald and McKenzie, loc. cit.).The a-compound was prepared by heating isobutylcarbinol (4.5 grams) with a 5 per cent. excess of nitrophthalic anhydride (9.4 grams) for 15 minutes on the water-bath, and then carefully for 5 minutes with the free flame. After addition of benzene to the hot solution, a finely crystalline crop of 8.5 grams separated on cooling, and when this was recrystallised several times from benzene i t melted a t 165-166’. On analysis :1138 McKENZIE : THE ESTERIFICATLON OF 0.5704, dried at 100' and dissolved in methyl alcohol, required 20.35 C.C. N/10 potassium hydroxide for neutralisation. C13H1506N requires 20.30 C.C. The ester is sparingly soluble in benzene and carbon tetrachloride, and is hydrolysed with much more difficulty than the P-isomeride. On theoretical grounds, the latter observation was to be expected, as the alcohol radicle in the a-ester is regarded as replacing the hydrogen of the stronger carboxyl group, and should therefore not be so easily detached as in the case of the /I-ester.2-d-AmyI-3-nitrophthc Acid. The corresponding p-ester has been described (Ioc. cit.). An acetone solution of it gave [a J:r + 6.5' (c = lo), and the I-amyl alcohol obtained from it had the rotation ay - 9-62' ; hence [ a]ip - 5.90'. The amyl alcohol used for the preparation of the a-ester was pre- pared by subjecting fuse1 oil (a, - 2 * 2 O , I = 2) to a modification of the Le Bel-Rogers' method, and then working up the product (a, - 6', I = 2) by treatment with 3-nitrophthalic acid (lac. cit.). A prolonged series of crystallisations yielded an ester with the rotation in acetone [ agf' + 5.9' for c= 10, but in this case the separation of the mixed crystals was not carried to the limit.The product, on hydrolysis, gave an alcohol with C Z ~ - 8-50' ( I = 2), which contained therefore 88.5 per cent, of I-amyl alcohol, This alcohol (9.8 grams) was heated with a 5 per cent. excess of nitrophthalic anhydride (20.5 grams) for 25 minutes on the water- bath, and then carefully with the free flame until the solution was clear. After treatment with benzene as before (p. 1137), 19.2 grams were obtained with the m. p. 156-158O and with the rotation in ace- tone solution [ a ] T + 2.2' for c = 8.3615. After recrystallisation from benzene, 17.9 grams (m. p. 157.5-158.5O) resulted, and a determination of the specific rotation in acetone solution gave the following result : I = 2, o = 8.256, a z + 0.37', [ a]": + 2.2".On analysis : 0-3945, dried at 100' and dissolved in methyl alcohol, required CI,H,,O,N 14.4 C.C. N/10 potassium hydroxide for neutralisation. requires 14.04 C.C. 0.1939 gave 0.0925 H,O and 0.3985 CO,. C,,H,,O,N requires H = 6.3 ; C = 55.5 per cent. Like the isomeric p-ester, this compound is beautifully crystalline. It dissolves at once in cold dilute ammonia solution, is very easily soluble in acetic ether or acetone, and easily in chloroform, but only I$ = 5.3 ; C = 56.0.3-NITROPHTHALIC ACID. 1139 sparingly in benzene or carbon disulphide. more difficulty than the P-ester. recrystallisation from benzene and from other solvents. It is hydrolysed with Its melting point was not raised on E~tter$cation.of AmyI AIcohoI 6y Nitrophthalic Anhydride. This experiment indicates the formation of a- and P-acid esters. An active amyl alcohol (33 grams, a 5 per cent. excess) with the rotation aD - 4.7' ( I = 2) was heated on the water-bath for 15 minutes with nitrophthalic anhydride (69 grams) until the mass became asolid paste, which was then cautiously heated with a free flame until the solution was clear. By treatment with benzene as before, and after recrystallisation of the resulting product from benzene, 55 grams were obtained ; this, on analysis, had the composition C,,H,,O,N. The specific rotation in acetone was [u]F + lalo (c= 8.1155). The pro- duct contained no normal ester, as it dissolved at once in cold dilute ammonia; it melted at 151-154", and an examination of the melting points of successive crops from benzene and other solvents showed that i t obviously presented a case of mixed crystals of the acid esters containing the a-compound in excess.The separation would have proved very tedious, and ma8 not in this case carried out. Systematic crys- tallisation of the benzene mother liquors yielded a product containing excess of the @ester, and crystallising from carbon disulphide in glassy, transparent prisms (m. p. 101-110'); a determination of its rotation in benzene gave [.ID + 5.9" for c = 3.5655. Ester$cation of AmyI AlcohoE by Nitrophthalic Acid. This experiment affords evidence for the production of a- and P-acid esters, and of the normal ester. The amyl alcohol used had the rotation uD - 6' ( I = 2), and contained therefore about 60 per cent, I-amyl alcohol.3-Nitrophthalic acid (89 grams) was heated on the xater-bath for 14 hours with amyl alcohol (178 grams) and sulphuric acid (26-7 grams). When the bulk of the mineral acid had been removed by washing with water, the amyl alcohol was separated by distillation under diminished pressure, and further esterified as before, in order to obtain a larger yield of crystalline esters. The alcohol removed after each esterification was markedly less laevorotatory than the original and this indicated that the active constituent was esterified more quickly than the inactive. The brown oil obtained from the two esterifications was warmed, and an excess of carbon disulphide added.After several hours, the crystals were drained off and washed with carbon disulphide. In this way, 80 grams of a mixture of the acid1 I 40 THE ESTERIFICATION OF 3-NITROPHTHALIC ACID. esters were obtained, from which 1-d-amyl-3-nitrophthalic acid may be separated (Zoc. cit.). From the carbon disulphide mother liquors, the carbon disulphide and the free amyl alcohol were removed by distillation in a current of steam. A calculated excess of sodium hydroxide was added to the residue, and the distillation in steam was continued until no more alcohol was observed to distil over. The residue in the flask, although alkaline, contained a heavy oil, which was separated, and proved to be the normal ester, and could only be hpdrolysed with difficulty. The amyl alcohol obtained from it by heating it with 33 per cent.sodium hydroxjde and then distilling in steam, weighed 22 grams, and had the rotation aD - 5.83" ( I = 2). For the formation of normal ester, compare Wegscheider and Lip- schitz (Zoc. cit,), and Graebe and Rostowzew (Ber., 1901, 34, 2107). Ester9cation of Methyl Alcohol 6y Nitrophthalic Anhydride. Nitrophthalic anhydride (38 grams) was heated on the water-bath under a reflux condenser for 2 hours with methyl alcohol (100 c.c.). After standing overnight, the alcohol was evaporated off, and a crystalline solid was obtained which was sparingly soluble in cold, but much more easily in hot water. A small portion of it dis- solved a t once in cold dilute ammonia, and therefore no normal ester was present. After one crystallisation from water, the air- dried substance weighed 40 grams, and a sample of it, dried at looo, melted very slightly between 138O and 145O, and mainly between 145O and 1 4 9 O . By repeated crystallisation, each time from much water, the melting point became very gradually sharper, whilst each crys- tallisation yielded glassy, prismatic needles, apparently uniform in crystalline form.The variations in melting point undoubtedly showed that the case was one of mixed crystals of the a- and P-acid esters, with the former in excess. The difficulty of separating the constituents of the mixture in such a case is exem- plified by the experience of Balbiano (Gaxxetta, 1876, 6, 229), and of Marckwald and the author (Zoc. cit.). The isolation of the a-compound was conducted by recrystallising the above product 25 times from water ; the progress of the separa- tion was observed by a determination of the melting point of each successive crop, dried a t looo. The sulphuric acid, in which the melting point tube was immersed, was kept in constant agitation, and the temperature, when nea.r the melting point, was not allowed to rise more than lo per minute.The points at which melting was just observable, and a t which the last trace of solid had disap- peared, were carefully noted by aid of a, lens. The melting pointsDERIVATIVES OF %NITROTOLY I,-4-HYDRAZINE. 1 14 1 were not corrected. Finally, 4 grams of the a-compound were obtained, the melting point of a portion of which, dried at looo, was 152-153". On analysis : 0.6237, dried in air, lost 0*0480 a t 105'. 05757 anhydrous substance, dissolved in methyl alcohol, required H,O = 7.7. C,H70,N + H,O requires H,O = 7.4 per cent. 25.7 C.C. N/10 potassium hydroxide for neutralisstion. C,H70,N requires 25.6 C.C. per cent. Wegscheider and Lipschitz (Monatsh., 1900,21 , 794), under different conditions from those just described, claim t o have obtained a 90 per cent. yield of the a-ester, and give its melting point as 144". On repetition of the esterification exactly under the conditions quoted by them, I was unable t o confirm their results. The phenomenon of mixed crystals was again evidenced. The a-ester was, however, isolated, and melted as before at 152-153'. On esterification of methyl alcohol by 3-nitrophthalic acid by the E. Fischer-Speier method and removal of the small amount of normal ester produced, a product was obtained which melting point determin- ations again indicated to consist of mixed crystals of the a- and ,@-acid esters. The separation of the p-ester was, however, not attempted. SECOND CEEMICAL INSTITUTE, UNIVERSITY OF BERLIN, AND JENNER INSTITUTE, LONDON.