View Article Online / Journal Homepage / Table of Contents for this issue 1126 HARDlNC3 AND WEIZMANN : SYNTHESIS OF XCIV.-Synthesis of 6-Carboxy-3: 4-dimethoxyphenyl- glyoxylic Acid. By VICTORJOHN HARDING and CHARLESWEIZMANN. AMONGthe products of the oxidation of trimethylbrazilin by means of warm potassium permanganate, there was found to occur a dibasic acid possessing the empirical formula C,,H,,O,. This acid, which was isolated and investigated in these laboratories by W. H. Perkin, jun., was shown to be 6-carboxy-3: 4-dimethoxy- phenylglyoxylic acid (I) [“ dimethoxycarboxybenzoylformic acid ”1 (Trans., 1902, 81, 1022). In the present communication the authors describe the synthesis of this acid from 4 : 5-dimethoxy-o-methyZacetophenone(11) : MeO/\C02H MeOAMe MeO/\Me MeOl ‘CO*C02H MeOI ICOMe Me01 /CO*CO,H \/ \/ \/ (1.1 (11.) (111.) This ketone is easily prepared by the condensation of acetyl chloride and homocatechol dimethyl ether by means of aluminium chloride. When oxidised by warm potassium permanganate there is first isolated 4 : 5-clinz,ethoxy-o-tolylgl~o~l~cacid (111). Further oxidation converts the methyl group into a carboxy-group, and leads to the production of 6-carboxy-3 : 4-dimethoxyphenylglyoxylic acid. Although it has not been found possible directly to compare the synthetical acid with that obtained from trimethylbrazilin, the Published on 01 January 1910. Downloaded by New York University 27/02/2016 21:27:57. authors do not think there can be much doubt as to their identity. The following are the properties of the synthetical acid: 1. Calcium cE’loride, with a neutral solution of the ammonium salt, gives no precipitate in the cold, but on warming, the crystalline calcium salt separates af; once. 2. The acid, separated by means of the calcium salt, crystallises with two molecules of water in small, brown, soluble prisms. 3. The silver salt is derived from the anhydrous acid. 4. The melting point of a specimen of acid dried in the water- oven was found to be 148O (Perkin gives 150O). With the exception of the slight difference in the melting point, these properties agree exactly with those described by Perkin (Zoc. cit.). As, however, a difference was found between the oxime of the synthetical acid and that obtained by Perkin, it was judged necessary to convert the synthetical product into some derivative which would determine absolutely the position of the oxalyl group, View Article Online 6-CARBOXY-3 : 4-DIMETHOXYPHENYI~GLYOXYLZCACID. 1J 27 because it is easily conceivable that an acid possessing the con- stitution : CO*CO,€I might show properties almost identical with the isomeric acid, as, indeed, is shown in the case of the two similarly isomeric hemipinic acids. In order to determine this point, the 6-carboxy-3: 4-cli- methoxyphenylglyoxylic acid was converted into m-hemipinic acid. This was accomplished by the distillation of the silver salt, by which method a quantitative yield of m-hemipinic anhydride was obtained. This proves beyond all doubt the constitution of the synthetical acid, and establishes its identity with the acid obtained by the oxidation of trimethylbrazilin. 4 : 5-Dimethoxy-o-methylacetophenone,when warmed in glacial acetic acid solution with a few drops of concentrated nitric acid, undergoes a remarkable reaction; the acetyl group is displaced by a nitro-group, with the production of nitrohomocatechol dimethyl ether : &f.P oqm3 nl.Oj/N 0, ' The displacement of a carboxy-group by a nitro-group is well known, and Salway (Trans., 1909, 95, 1155) has shown that the aldehyde group can also be displaced by a nitro-group. The displace- ment of an acetyl group by a nitro-group, however, does not seem to have been previously observed, and it is hoped shortly to com- municate the results of investigations in this direction. It is Published on 01 January 1910. Downloaded by New York University 27/02/2016 21:27:57. worthy of note that the displacement of the acetyl group can be effected by warm dilute aqueous nitric acid, the temperature of the reaction and concentration of the acid apparently having very little influence on the displaccment. E x P E R I M E N T A L. 4 : 5-I) ini e thoz y-o-m e t hy lu c e t ophen,on e, C,H,Me (0Me) CO Me. This ketone is easily obtained by condensing acetyl chloride (30 grams) with homocatechol dimethyl ether (50 grams), dissolved in 200 C.C. of carbon disulpliide, by means of aluminium chloride (100 grams). The reaction is maintained at the ordinary tem- perature for twenty-four hours, when it is heated for a further two hours on the water-bath. The dark red product is decom- posed by water, and the carbon disulphide removed by distillation in a current of steam. The dark brown residual oil is then View Article Online 1128 HARDING AND WEIZMANN : SYNTHESIS OF extracted by means of ether, washed with a dilute solution of potassium hydroxide, dried, and distilled. The ketone, which distils at 204O/70 mm., rapidly solidifies in the receiver, and is purified by crystallisation from methyl alcohol or light petroleum of high boiling point : 0.1409 gave 0.3503 CO, and 0.0941 H,O. C=67.7; H=7.4. CllH140, requires C = 68.0 ; H = 7.3 per cent. 4 : 5-Dimethoxy-o-metl~ylacetop7~enonecrystallises in short, colour- less needles, melting at 68O. It possesses an aromatic odour, recall- ing that of homocatechol dimethyl ether. The phenylhydrazone, prepared in the usual way, crystallises from acetic acid. It shrinks together at 168O, and decomposes at 170° : 0.2020 gave 18.5 C.C. N, (moist) at 17O and 725 nim. N=10*1. C17H,,0,N2 requires N = 9.9 per cent. The semicarbazone decomposes at 186O. Pipe~onylidene-4: 5-~im.et7~oxy-o-met7aylaceto~~~~enone, C,H,MeCOMe,) *CO*CH:CH*C,H,:O,: CH,. This derivative is prepared by dissolving molecular quantities of 4 : 5-dimethoxy-o-methylacet~phenoneand piperonal in methyl alcohol, adding a few drops of 50 per cent. aqueous potassium hydroxide, and boiling for a short time. On dilution with water, the resulting oil solidifies after some time. This is collected and crystallised from alcohol, from which it separates in golden-yellow needles, melting at 108-109° : 0.1152 gave 0’2916 CO, and 0.0602 H,O. C = 69.1 ; H =5.8. C,9H,80, requires C = 69.6 ; H = 5.5 per cent.. Published on 01 January 1910. Downloaded by New York University 27/02/2016 21:27:57. Oxidation of 4 : 5-Dimethoxy-o-rr~~ethylacetophenoneby means of Alkaline Potassium Permangunate. A.-Fornaation of 4 : 5-Dinsqethoxy-o-tolylglgoxylic Acid, C,H,Me(OMe)z*CO C0,H. Ten grams of 4 : 5-dimetlioxy-o-methylacetophenoneare added to 8 grams of sodium carbonate dissolved in 100 C.C. of water, and heated on the water-bath. Sixty grams of potassium permanganate, dissolved in 600 C.C. of water, are then added. The oxidation proceeds slowly. When the pink colour of the permanganate has disappeared, the manganese dioxide is collected, washed several times with boiling water, and the combined filtrates are evaporated to a small bulk on the water-bath. On acidifying with hydro- chloric acid, 4 : 5 -dimethoxy-o-tolylglyoxylic acid gradually crys- tallises out. After recrystallisation from hot water, it melts at 155O. View Article Online 6-CARBOXY-Q : 4-DINETHOXYPHENYLGLYOXYLIC ACID. 1129 0.1130 gave 0.2434 CO, and 0.0520 H20. C=58*8; H=5.1. C,,H,,O, requires C = 58.9 ; H = 5.3 per cent. 4 : 5-Dimethox~-o-toZylgZ~ox~licacid crystallises from water in short needles, and is insoluble in cold benzene. Its solution in concentrated sulphuric acid develops a cherry-red colour. B.-Synthesis of 6-Curb oxy-3 : 4-d.i~net7~oxyphenyZglyoxyZ~cAcid, C0,H*C,H2(0Me),*CO*C0,H. This acid is obtained by the oxidation of 4 : 5-dimethoxy-o-methyl- acetophenone under the following conditions. The ketone (20 grams) is added to sodium carbonate (15 grams) dissolved in water (100 c.c.), and a 10 per cent. solution of potassium permanganate (150 grams) added gradually, the operation being conducted on the water-bath. When the oxidation is complete, the manganese dioxide is collected, extracted several times with boiIing water, and the combined filtrates and washings are evaporated to a very small bulk, acidified with hydrochloric acid, mixed with sand, and then evaporated to complete dryness. The dry mass is then extracted by means of ether in a Soxhlet apparatus, and on evaporating the ethereal extract a viscid liquid is obtained, which crystallises after some time. The silver salt was prepared for analysis, and, as observed by Perkin (Trans., 1902, 81, 1023), is derived from the anhydrous acid. (Found, C = 28.2 ; H = 1.7 ; Ag = 45.8. Calc., C=28*2; H=1.7; Ag=46.1 per cent.) In order to prepare an acid corresponding exactly in properties with that described by Perkin (Zoc. cit.), a portion of the crude oily acid, obtained direct from the oxidation, was dissolved in water, neutralised with ammonia, and boiled with a solution of calcium chloride. The Published on 01 January 1910. Downloaded by New York University 27/02/2016 21:27:57. calcium salt, which separated during the heating, was collected and decomposed by hydrochloric acid, when, after some time, the 6-carbbxy-3 : 4-dimethoxyplienylglyoxylic acid crystallised in small, brown prisms. These were collected and dried on porous porcelain in the air for twenty-four hours. (Found, C = 45.0 ; H = 4.5.