NITRATION OF 2-ACETYLAMINO-Q 4-DIMETHOXYBENZOIC ACID. 69 1 X . - The Nitration of 2 -A ce t y 1 a mino - 3 4 - d irne t hoxy -benxoic Acid and 3- Acetylaminoveratrole. By CHARLES STANLEY GIBSON JOHN LIONEL SIMONSEN and MADYAR GOPALA RAU.* IN a recent communication (T. 1915 107 SZS) Simonsen and Nayak described experiments on the nitration of 3-acetylamino-2-methoxytoluene which were undertaken with the object of synthesising 4-nitro-2 3-dimethoxybenzoic acid. Since the isomeric nitroamines obtained could not be converted into the correspond-ing nitrophenols the investigation did not lead to the desired result and i t therefore occurred t o us that if 6-nitro-3-amino-veratrole could be prepared it would readily yield the required acid on displacement of the amino-group by a carboxyl group.With this object in view we have examined the action of nitric acid on 2-acetylamino-3 4-dimethoxybenzoic acid (I) and 3-acetyl-aminoveratrole (IV) and although the reaction has not proceeded in the manner expected,+ it has yielded results of some interest. * An abstract of this paper was read a t the Third Indian Science Congress held in Lucknow on January 14th 1916. t Since the paper was prepared for publication (March 1916) we have received from Professor Majima a copy of a paper by Majima and Okazaki (Sci. Rep. Tdhoku Imp. Univ. 1916,5 215) in which the synthesis of 4-nitro-2 3-dimethoxybenzoic acid is described. The same authors have also shown the 5 6-dinitro-2 3-dimethoxytoluene prepared by Cain and Simonsen (ZOC. cit.) to be the 4 6-dinitro-isomeride 70 GIBSON SIMONSEN AND RAU THE NITRATION OF \ When 2-acetylamino-3 4-dimethoxybenzoic acid (I) was nitrated (see p.74) the sole product of the reaction was found to be 6-?~itro-2-ucetylarr~ino-3 4-dimethoxyl1 enzoic acid (11). The con-stitution of this acid was proved by the fact that on hydrolysis it lost carbon dioxide and yielded 5-nitro-3-aminoveratrole which on elimination of the amino-group gave 4-nitroveratrole. 5-Nitro-3-arninoveratrole has also been obtained in the form of its acetyl derivative by the nitration of 3-acetylaminoveratrole (IV) and this is probably the simplest method for the preparation of this substance. When 5-nitro-3-aminoveratrole was diazotised and treated with cuprous cyanide it yielded 5-nitro-2 3-dimethoxyb enzonitde (V), which on hydrolysis gave 5-nitro-2 3-dimethoxybenzoic acid (VI).This acid was found to be identical in every respect with the acid previously described by Cain and Simonsen (T. 1914 105 159),* and there can therefore be no doubt as t o its constitution. I n view of the discrepancy as to the melting point of 6-nitro-2 3-dimethoxybenzoic acid Perkin and Robinson (T. 1914 105, 2390) stating that it melted a t 178-5O whereas Wegscheider and Klemenc (Monatsh. 1910 31 709) gave 189O we have thought it advisable to prepare this acid by the methods given by these * The melting point of 5-nitro-2 3-dimethoxytoluene should be read 75-76O and not 176-176" ELE is given in this paper 2-ACETYLARIINO-3 4-DIMETHOXYBENZOIC ACID ETC. 7 1 investigators and also to compare it with the acid prepared by Cain and Simonsen (loc.cit.). We have found that the acid pre-pared by any of these three methods melts a t 185-186O (corr.), and it would therefore appear that the melting point found by Perkin and Robinson was somewhat low. When 2-acetylamino-3 4-dimethoxybenzoic acid was nitrated under conditions slightly different from those which were found to give a nearly quantitative yield of the nitro-acid a substance was obtained which decomposed a t 241° and is considered to be 4 5-dinitro-3-acetylarninoweratrole (VII). This substance was also formed together with an isomeride 5 6-dinitro-3-acetyiarnino-veratrole (VIII) when either 3-acetylaminoveratrole (IV) or 5-nitro-3-acetylaminoveratrole (111) was nitrated with fuming nitric acid.The constitution of the substance decomposing a t 241O was proved by the fact that on displacement of the amino-group by hydrogen 4 5-dinitroveratrole was obtained whilst the constitu-tion of the isomeride may be directly deduced from its prepara-tion by the nitration of 5-nitro-3-acetylaminoveratrole. 4 5-Dinitro-3-acetylaminoveratrole was found to be a substance of considerable interest. It was soluble in sodium hydroxide or barium hydroxide solution giving a yellow solution which slowly became red on keeping. It was reprecipitated unchanged on the addition of dilute acids or on passing carbon dioxide through a solution of its salts so that it behaved like a phenol. So far as we are aware this is the first secondary amine of this type namely, an acetylamine which has been found to possess this property of forming salts.Other secondary amines soluble in alkali are of course well known and we may mention as an example picryl-aniline and even picrylmethylaniline (compare T. 1906 89 583 ; Bey. 1910 43 1549) although the latter belongs t o a somewhat different type being a tertiary amine. That the acidic properties are connected with the secondary amino-group is shown by the fact that the amine 4 5-dinitro-3-aminoveratrole was quite insoluble in alkali. The salt may be represented by the two formulz (X) and (XI) : OMe /\OM 72 GIBSON SIMONSEN AND RAU THE NITRATION OF and we are inclined to the view that formula (X) is the more probable since the solution of the freshly prepared salt is yellow, whereas one would expect an ortho-quinonoid salt of formula (XI) to be deeply coloured.It is possible that the red colour which developed on keeping the yeIlow solution of the salt may be due to the slow formation of a salt having the quinonoid structure. It is interesting to note that 5 6-dinitro-3-acetylaminoveratrole was found to be quite insoluble in alkali and this difference in properties between the two isomerides afforded a simple method for their separation. I n a series of papers Meldola and his collaborators have shown that when nitromethoxyamines are diazotised under suitable con-ditions the nitro-group in the ortho- or para-position with respect to the amino-group is eliminated and may be replaced by a halogen. Thus for example Meldola and Eyre (T.1902 81, 989) have shown that dinitro-p-anisidine (XII) yields chloronitro-anisole (XIII). OMe OMe OMe (XiI). (XIII.) (XIV.) OMe OMe Cl (XV.1 (XVI.) So far as material has permitted we have investigated the products obtained by diazotising the two dinitroamines described in this paper. We have found that 4 5-dinitro-3-aminoveratroIe, when diazotised in acetic acid and sulphuric acid solution readily couples with &naphthol yielding the azo-dye which was found to be a strong phenol and we consider it to be best represented by formula (XIV) one of the methoxy-groups having undergone hydrolysis. When the amine was diazotised in a mixture of acetic and hydrochloric acids and the resulting diazonium salt heated with alcohol a halogenated phenol was obtained one of the nitro-groups having been eliminated.To this substance from a consideration of Meldola's results we ascribe formula (XV) although owing t o the small amount. of material available we can offer no direct evidence in support of this constitution. When 5 6-dinitro-3-aminoveratrole was diazotised with amy 2-ACETYLAMINO-Q 4-DIMETHOXYBENZOIC ACID ETC. 73 nitrite in absolute alcoholic solution the main product of the reaction was a substance which crystallised from alcohol in which i t was somewhat sparingly soluble and melted a t 1 8 1 O . I n spite of the somewhat high melting point we consider this substance to be 3 4-dinitroi~eratrole (XVI) and the molecular weight deter-mined by Barger’s method supported this view.At the same time, a small quantity of a phenol was isolated which on methylation gave a methyl ether melting a t 89-90O; for this substance we are unable t o suggest a formula. The results described in this paper seem to be of some interest from the point of view of orientation in the benzene ring. It will be observed that on nitrating both 2-acetylamino-3 4-dimethoxy-beiizoic acid and 3-acetylaminoveratrole it is the methoxy-group in the ortho-position with respect to the acetylamino-group that appears to exercise the sole directing influence the nitro-group entering the para-position with respect to this methoxy-group. The second nitro-group then assumes mainly the para-position with respect t o the other methoxy-group only a small quantity of the 5 6-dinitro-derivative being formed.If we ascribe the directing influence to the subsidiary valencies of the methoxy-group i t would then appear that such valencies are much intensified by the juxta-position of the positive acetylamino-group. This is the exact opposite to the results observed when the methoxy-group has a negative group in the ortho-position with respect to it since as has been shown by Perkin and Robinson (loc. cit.) o-veratraldehyde (XVII) on nitration gives as sole pro-duct a nitro-derivative (XVIII) in which the nitro-group has entered the para-position with respect to the methoxy-group furthest away from the negative group. (XVII.) (XVIII.) (XTX.) I n fact as Prof. Robinson has kindly informed us i t has been observed in a large number of cases examined by him that when a negative group is in the ortho- or para-position with respect to a positive group it neutralises such a group and the orientating effect is exercised by the second positive group.That this view cannot be of quite general application is however proved by the fact t$hat Cain and Simonsen (loc. cit.) found that o-veratric acid (XIX) gave on nitration 5-nitro-2 3dimethoxybenzoic acid (XX) 74 GIBSON SIMONSEN AND RAU THE NITRATION OF EXPERIMENT A L. Nitration of 2-Acetylnmino-3 4-dimethoxybenzoic Acid (I).* 6-Nitro-2-amino-3 4-dime t hoxy b enzoic A cid. The following method was found to give an almost quantitative yield of the above-mentioned nitro-acid. To a well-cooled mixture of nitric acid (D 1.4; 9 c.c.) and sulphuric acid (6 c.c.) 2-acetyl-amino-3 4-dimethoxybenzoic acid (3 grams) was gradually added with vigorous stirring.The acid slowly passed into solution and after ten minutes the mixture was poured on ice. A clear solu-tion was thus obtained which gradually became cloudy and the nitro-acid was deposited in fine pale yellow crystals. These were collected and purified by crystallisation from water containing a little alcohol. (Yield 3-5 grams.) For analysis the acid was dried at looo -f 0.1000 gave 0.1708 CO and 0.0398 H20. 0.1715 , 15.8 C.C. N a t 33O and 756 mm. N=9*7. C,,H,,07N2 requires C = 46.5 ; H = 4.2 ; N = 9.8 per cent. 6-Nitro-2-acetylamino-3 4-dimethoxybenzoic acid crystallises in very pale yellow prismatic needles which soften a t 215O and decompose a t 220O.It is very sparingly soluble in cold water, benzene ethyl acetate or chloroform but more readily so in acetone or hot water and very readily so in alcohol. On titration with a standard solution of barium hydroxide, 0.0812 gram neutralised 0.0247 gram of Ba(OH), whereas a mono-basic acid C11H1207N2 should require 0.0245 gram. The silver salt is very readily soluble in water but separates from an aqueous solution on the addition of alcohol in fine yellow needles : C=46.6; H=4.4. 0.1491 gave 0.0414 Ag. Ag=27.8. C,,H,,07N,Ag requires Ag= 27.6 per cent. * The acetylamino-acid was prepared by the method described by Pschorr and Sumuleanu (Bey. 1899 32 3411) when it was obt.ained in colourless plates which decomposed at 195-196". (FoundC=55.8; H=5.5; Ac= 18.0; Calc.C=55.2; H ~ 6 . 4 ; Ac-18-0 per cent.). It was stated by Pschorr and Sumuleanu to melt a t 191" and to crystallise in needles. On one occasion we obtained the acid in the form of needles which decomposed at 195-196" and the substance would therefore appear to be dimorphous (compare Chattaway and Lambert T. 1915,107 1766). t With the majority of substances described in this paper considerable difficulty was experienced in obtaining accurate analytical results. It was found necsssary to carry out the combustions very slowly and to interpose a U-tube filled with pumice moistened with sulphuric acid between the calcium chloride tube and the carbon dioxide absorption apparatus (compare Kletz and Lapworth T. 1915,107 1259) 2-ACETYLAMINO-3 4-DIMETHOXYBENZOIC ACID ETC.75 6-Nitro-2-amino-3 4-dimethoxybenzoic A cid. Much difficulty was a t first experienced in hydrolysing the acetyl group in the nitroacetylamino-acid since alkaline hydrolysis resulted in the formation of uncrystallisable oils whereas hydro-lysis with hydrochloric acid eliminated simultaneously the carboxyl group (see below). When however the acetylamino-acid was mixed with three times its weight of concentrated sulphuric acid and heated on the water-bath for half an hour hydrolysis readily took place a deep red solution being obtained. This was cautiously added to cold water and the excess of mineral acid removed by the addition of ammonia when a pale brown solid separated. This was collected and purified by repeated crystallisa-tion from ethyl acetate: 0.0728 gave 0.1186 CO and 0.0302 H,O.0.1283 , 14.4 C.C. N2 a t 30° and 760 mm. N=12*0. C,H,,0,N2 requires C=44-6; R=4*1; N=11-6 per cent. 6-Nitro-2-amino-2 4-&met hoxy b enzoic acid crystallises in pale yellow glistening needles which soften a t 185O and decompose a t 194-195O. It is readily soluble in alcohol or acetone somewhat readily so in ethyl acetate and very sparingly so in water benzene, or chloroform. It is a weak base being soluble in concentrated mineral acids separating however on dilution with water. C=44*4; R=4.6. 5-Ni t ro-3-aminovera t rol e (111). For the preparation of this substance 6-nitro-2-acetylamino-3 4-dimethoxybenzoic acid (3 grams) was mixed with hydrochloric acid (50 per cent.; 30 c.c.) and heated for two hours in a reflux apparatus.The excess of acid was removed on the water-bath, and the aqueous solution of the hydrochloride basified with ammonia when the nitroamine separated as a brown crystalline powder. This was collected and purified by crystallisation from dilute methyl alcohol when i t was obtained in pale brown pris-matic needles melting a t 105-106° : 0.1036 gave 0.1845 CO and 0.0498 H,O. C,H,,0,N2 requires C = 48.5 ; H = 5.3 per cent. 5-Nitro-3-aminoveratroZe is readily soluble in most organic solvents but only sparingly so in cold water more readily in hot water. The hydro-chloride and the sulphate are somewhat sparingly soluble in water. The platinichloride was obtained as a very sparingly soluble, microcrystalline yellow powder : C?=48.6; H=5.3.It does not appear to be volatile in steam 76 GIBSON SIMONSEN AND RAU THE NITRATION OF 0.0905 gave 0.0216 Pt. Pt=23*9. The acetyl derivative' separated from alcohol in faintly yellow, 0.1075 gave 0.198 CO and 0.0464 H,O. The b enzoyl derivative crystallised from acetic acid in colour-0.1645 gave 15.2 C.C. N a t 30° and 760 mm. (C,H,,04N2HC1),PtCl requires Pt = 24.1 per cent. glistening leaflets melting a t 172-173O : C-50.2; H2=4*8. C,,H,,O,N requires C = 50.0 ; H = 5.0 per cent. less glistening needles which melted a t 145-146O : C,,H,,0,N2 requires N'= 9.3 per cent. N=9.7. Dinzotisation of 5-Nitro-3-aminoveratrole. I. Formation of 4-Nitroveratrole. I n carrying out this experiment the nitroamine (0.5 gram) was dissolved in alcohol (5 c.c.) and sulphuric acid (0.5 gram) was added when the sparingly soluble sulphate separated in glisten-ing leaflets.To the well-cooled solution amyl nitrite (0.7 gram) was slowly added when the sulphate gradually passed into solu-tion. When the reaction was complete the clear solittion was carefully heated on the water-bath until all evolution of nitrogen had ceased. On pouring into water 4-nitroveratrole separated as an oil which rapidly solidified. It was crystallised from methyl alcohol when it was obtained in fine needles melting a t 95-96O, and this melting point was unaltered on admixture with a speci-men of 4-nitroveratrole from another source. 11. For m,rr I 1'0 ?a of 5 -Nit r 0-2 3-dim e tho my b e ti zo ti i t ril e (IV) . The amine (3 grams) was mixed with dilute sulphuric acid (H,S04 5 grams) when the sparingly soluble sulphate separated.This was diazotised in the usual manner with sodium nitrite and the clear liquid was gradually added t o a hot solution of cuprous cyanide (potassium cyanide 4.2 grains ; copper sulphate 3.7 grams). The mixture was heated on the water-bath until no more nitrogen was evolved (about thirty minutes) and the brown solid which had separated was dissolved in ether the ethereal solution filtered to remove a little insoluble resin washed with alkali to remove any phenol formed dried and evaporated when the nitrile was obtained as a brown powder (2.1 grams). It was purified by repeated crystallisation from dilute methyl alcohol with the aid of animal charcoal when i t was obtained in pale brown prismati 8-ACETYLAMINO-3 4-DIMETHOXYBENZOIC ACID ETC.77 needles which melted at about 127-128O but it is doubtful if it was quite pure. It was readily soluble in most organic solvents: 0.1304 gave 15.7 C.C. N at 30° and 752 mm. N=12.9. C9H,0,N requires N = 13.4 per cent. Hydrolysis of 5-Nitro-2 3-dimethoxybenzonitrde. The hydrolysis of the nitrile to the corresponding acid offered much difficulty and ultimately the following method was adopted although the yield was by no means satisfactory. The nitrile (1 gram) was mixed with barium hydroxide (3 grams) dissolved in water (10 c.c.) and heated in a reflux apparatus for three hours when all evolution of ammonia had ceased. The brown solution was filtered from a little resinous matter and acidified when a pale yellow solid separated and was collected.This was found to consist of a phenolic acid mixed with a little of the dimethoxy-acid the aqueous solution giving a deep red colour with ferric chloride. The crude acid was converted into the scarlet potassium salt and the dry salt heated with excess of methyl sulphate in a stoppered bottle on the water-bath the treat-ment being repeated three times when the greater part of the phendlic acid was methylated. The acid obtained in this manner was dissolved in dilute sodium carbonate solution and oxidised on the water-bath with potassium permanganate in order to remove any unmethylahd phenolic acid. After filtering off the man-ganese dioxide the solution was concentrated and acidified when 5-nitro-2 3-dimethoxybenzoic acid (VI) separated.This was collected and crystaIlised from hot water when it melted a t 174-175O and was found to be identical in every way with the acid obtained by Cain and Simonsen (Zoc. cit.). The ethyl ester melted a t 78-79O and this melting point was unaltered on admixture with an equal amount of the ethyl ester which had been prepared by Cain and Simonsen. The methyl ester crystallised from dilute methyl alcohol in fine needles melting at 76-77O. As this melting point was only slightly different from that of the methyl ester of the isomeric 6-nitro-acid a mixture of equal parts of these two esters was made, and was found to' melt indefinitely a t about 60°. (Found: N= 6.4. It is of interest to note that the methyl ester has apparently a lower melting point than the ethyl ester which is somewhat unusual (compare Meyer " Analyse und Konstitutionsermittelung organischer Verbindungen," p.107) Calc. N=5*8 per cent. 78 QIBSON SIMONSEN AND RAW THE NITRATION OF 6-Nitro-2 3-dirnethoxyber~aoic Acid. As has already been mentioned (see p. 70) in view of the different melting points obtained for this acid we have prepared it by the methods of Wegscheider and Klemenc and also by that of Perkin and Robinson. The acid prepared by either of these methods separated from water in leaflets melting a t 184-185° (corr.). The methyl ester was also prepared and melted a t 78-79O (Perkin and Robinson give 8l0) and this melting point was unaltered on admixture with a specimen of the methyl ester of this acid prepared by Cain and Simonsen.There can therefore be no doubt that the acid obtained by these three methods is identical. 4 5-Dinit ro-%ace t ylalrni~overatrole (VII). If the conditions adopted for the nitration of 2-acetylamino-3 4-dimethoxybenzoic acid are slightly varied then in addition to the formation of 6-nitro-2-acetylamino-3 4-dimethoxybenzoic acid a substance was obtained which f o r reasons already given (see p. 71) is considered to be 4 5-dinitro-3-acetylaminoveratrole. I n one experiment the acetylamino-acid (22 grams) was added to a well-cooled mixture of nitric acid (D 1.4; 44 grams) and sulphuric acid (88 grams); the solution became deep red and a vigorous evolution of gas was observed. After fifteen minutes, the mixture was poured on ice and the solid ( A ) which separated was immediately collected.The filtrate on keeping desposited a further quantity of solid (3 grams) which was found to be nearly pure 6-nitro-2-acetylamino-3 4-dimethoxybenzoic acid. On extraction with ether the filtrate yielded a small quantity of an acid (0.6 gram) which crystallised from hot water in colourless, prismatic needles decomposing a t 191O. Unfortunately a sufficient amount of this acid could not be obtained for a detailed examina-tion to be made. The main product of the nitration ( A ) was dissolved in dilute sodium hydroxide and the deep reddish-brown solution was saturated with carbon dioxide when a colourless solid separated (3.8 grams).* This was collected and purified by crystallisation from alcohol when 4 5-&nitro-3-acetylaminoveratrole separated in long glistening colourless needles which decomposed a t 241O : 0'123 gave 0.191 CO and 0.0413 H,O.C=42*3; H=3*7. 0.1865 , 26.2 C.C. N a t 33O and 759 mm. N=14.9. C,,H,,O7N3 requires C=42*1; H = 3.8 ; N = 14.7 per cent. * The sodium carbonate solution on acidification yielded a further quantity of 6-nitro-2-acetylamino-3 4-dimethoxybenzoic acid 2-ACETYLAMINO-Q 4-DIMETROXYBENZOIC ACID ETC. 79 The substance is readily soluble in sodium hydroxide or barium hydroxide yielding a yellow solution which becomes red on keep-ing. When 4 5-dinitro-3-acetylaminoveratrole was heated for one hour with acetic anhydride containing a little pyridine and the acetic anhydride removed in a vacuum 4 5-dinitro-3-diacetylamino-veratrole was obt'ained.This substance which was readily soluble in most organic solvents was purified by repeated crystallisatioii from benzene when i t was obtained in faintly yellow prisms melt-ing a t 130-131O: With ferric chloride it gives no coloration. 0.1042 gave 0.1700 GO and 0.0384 H,O. Cl2HI3O8N3 requires C = 44.0 ; H = 3.9 per cent. 4 5-Dinitro-3-diacetylaminoveratrole was found to be quite insoluble in alkali; it was somewhat readily hydrolysed to the monoacetylamine. C =44-4 ; H,=4.0. 4 5-Dinitro-3-aminoverat rol e. This substance was readily obtained by dissolving the acetyl-amino-derivative in concentrated sulphuric acid and heating for not more than ten minutes a t looo when on pouring into water, the amine separated as a flocculent powder.It was purified by crystallisation from methyJ alcohol : 0.1066 gave 0-1553 CO and 0.0384 H,O. 4 5-Dinitro-3-ami~ove~atrole crystallises in terra-cotta needles melting at 112-113O. It is insoluble in alkali but dissolves in hot concentrated hydrochloric acid being reprecipitated on dilu-tion. C=39.7; E=4.0. C8H,0,N3 requires C= 39.5 ; H = 3.7 per cent. 3-A minoveratrole (IV). The following method was found to give an excellent yield. 2-Amino-3 4-dimethoxybenzoic acid (10 grams) was suspended in glycerol (90 per cent.; 50 grams) and the mixture heated in an oil-bath a t 170-180° when the acid gradually passed into solu-tion and a vigorous reaction took place with the evolution of carbon dioxide. After keeping a t this temperature for thirty minutes the mixture was heated a t 215O for fifteen minutes cooled, and mixed with water when the amine separated as an oil.This was dissolved in ether the ether dried and evaporated and the residual oil fractionated under diminished pressure : 0.0924 gave 0.2134 CO and 0.0568 H,O. 3-Arninoveratrole is a colourless oil which boils at 137O/10 mm., C=62.9; H=6-9. C8Hl,0zN requires c= 62.7 ; H = 7.2 per cent 80 GIBSON SIMONSEN AND RAU THE NITRATION OF and possesses a faint odoar reminiscent of aniline. to the air it rapidly darkens in colour. steam and somewhat readily soluble in water. On exposure It is readily volatile in The picrate crystallises from alcohol in needles melting at 0.1015 gave 14.5 C.C. N a t 29O and 760 mm.The acetyl derivative separates from hot water in which it is 0.1443 gave 9.8 C.C. N a t 30° and 760 mm. The b ensoyl derivative crystallises from alcohol in glistening, 0-1094 gave 6.0 C.C. N a t 30° and 762 mm. 173-175': N=14.9. C8H,,0,N,C,H30,N3 requires N = 14.7 per cent. readily soluble in well-formed cubes melting a t 8 5 O : N=7-3. C,,H,303N requires N = 7.2 per cent. striated needles melting a t 1 0 7 O : N=5*9. C,,H,,03N requires N = 5.4 per cent. A'itration of 3-9 cetylami,zoveratrole. I . Forination of 5-Nitro-3-acet ylaminov erntrole (111). 3-Acetylaminoveratrole (1 gram) was added gradually with vigorous stirring to well-cooled nitric acid (D 1.4; 5 grams); the acetylamine gradually passed into solution and the nitro-deriv-ative crystallised out the whole mass becoming pasty.After fifteen minutes the mixture was poured on ice and the nitroacetyl-amine collected. (Yield 0.85 gram.) The 5-nitro-3-acetylamino-veratrole prepared in this manner crystallised in the glistening leaflets characteristic of this substance melted a t 172-1 73O and was found to be identical in every way with the acetylamine described above (see p. 76). On hydrolysis it yielded the nitro-amine melting a t 105-106°. 11. Formation of 4 ; 5-Dinitro-3-acetylaminoveratrole ( V I I ) and 5 6-Dir~itro-3-acetylaminoveratrole ( V I I I ) . 3-Acetylaminoveratrole (1 7 grams) was gradually added to nitric acid (D 1-52; 60 grams) which was well cooled in a freez-ing mixture the temperature not being allowed t o rise above 0".The acetylamine dissolved in the nitric acid with a hissing sound, and towards the end of the reaction the liquid became pasty owing to the crystallisation of the products of the nitration. After keep-ing for fifteen minutes the mixture was poured on ice and the solid was collected. The crude product obtained in this manner was repeatedly ground up with small quantities of dilute sodium hydroxide solu-tion until nothing further was dissolved. The insoluble portio 2-ACETYLL4MINO-3 4-DIMETHOXY BENZOIC ACID ETC. 81 was collected and the filtrate was reserved for further examina-tion (see below). The residue was purified by crystallisation froiii alcohol when it was obtained in faintly yellow needles melting a t 178-179O. (Yield 4.7 grams) : 0.1016 gave 0.1555 CO and 0.0365 H,O.5 6-Dinitro-3-acetylamino~1eratrole was found to differ from its isomeride in being quite insoluble in alkali. 5 6-Dinitro-3-aminoveratrole was readily obtained by hydrolysing the acetyl derivative with concentrated sulphuric acid. It crystal-lised from dilute alcohol in long yellow prismatic needles melting a t 141-142O. It appeared to be a somewhat stronger base than its isomeride its salts however being readily dissociated by water : 0.1039 gave 0.1504 CO and 0.0366 H,O. C,H,O,N requires C = 39-5 ; H = 3.7 per cent. The alkaline filtrate from which the 5 6-dinitro-3-acetylamino-veratrole had been separated was acidified and the solid which separated was collected. (Yield 11.4 grams.) It was purified by crystallisation from alcohol when it was obtained in colourless needles decomposing a t 241° and was found to be 4:5-dinitro-3-acetylarninoveratrole.(Found C = 42.4 ; H = 3.9. Calc. C = 4 2 1 ; 11-3.8 per cent.) C=41*9; H=3*9. Cl,H1,0,N3 requires C = 42.1 ; H = 3.8 per cent. C=39*5; H=3-9. Nitru tiom of 5-Nitro-3-ace t ylumii~ov era t role (111). 5-Nitro-3-acetylaminoveratrole was nitrated with nitric acid (D 1.52) under the conditions just described. The products were separated by means of alkali when from 0.3 gram of the nitro-acetylaniine 0.24 gram of the 4:5-dinitro- and 0.1 gram of the 5 6-dinitro-isomeride were isolated. Diuzotisution of 4 5-Dinitro-3-amii~overatrole. I. Formutiou of 4 5-Dinitroueratrole. The base (1.65 grams) was dissolved in alcohol (15 c.c.) and after the addition of sulphuric acid (1 gram) amyl nitrite (1.5 grams) was gradually added t o the well-cooled mixture when the sparingly soluble sulphate slowly dissolved.When the diazotisation was complete zinc dust (0.2 gram) was added and the mixture heated in a bbiling-water bath until the evolution of nitrogen was com-plete. The filtered solution was poured into water and the reddish-brown semi-solid oil which separated was dissolved in ether. The ethereal solution was washed with dilute alkali to remove the phenol dried and evaporated when a small quantity of a sub-stance was isolated which crystallised from methyl alcohol in VOL. CXI. 82 GIBSON SIMONSEN AND RAU THE NITRATION OF leaflets melt,ing a t about 140O. It was not obtained in sufficient quantity for analysis.The alkaline solution on acidification yielded a phenol which was not purified but was methylated in the usual manner with methyl sulphate when the methyl ether was obtained as a brown powder. This was crystallised from dilute acetic acid when it separated in yellow needles melting a t 127-128O and evidently consisted of 4 5-dinitroveratrole since the melting point was not depressed on admixture with a specimen of this substance from another source. (Found N= 12.6. Calc. N= 12.3 per cent.) 11. 4 5-Dinitro-2 -h ydrox y-1 -m e t hox y-3-az o-fl-naph t hot (XIV) . For the preparation of this substance the amine (1 gram) was dissolved in acetic acid (5 c.c.) and after the addition of sulphuric acid (0.8 gram) a solution of sodium nitrite (0.2 gram) was added to the well-cooled solution.The mixture was carefully added to an alkaline solution of &naphthol and the sparingly soluble indigo-blue sodium salt which separated was collected and decomposed with dilute acetic acid. The reddish-brown azo-compound was purified by repeated crystallisation from pyridine when i t was obtained in purple leaflets with a golden bronze metallic reflex decomposing a t 222O : 0.105 gave 0.2037 CO and 0.0342 H,O. The substance was found to be a strong phenol being readily soluble in dilute alkali yielding a reddish-purple solution so that there can be little doubt that one of the methoxy-groups had undergone hydrolysis. I n sulphuric acid it dissolved yielding a purple solution which became red on dilution.C=52.9; H=3*6. C,,H,,O,N requires C= 53-1 ; H = 3.1 per cent. 111. 4-Chloro-5-nitroguuiacol (XV). I n one experiment, the amine (1 gram) was dissolved in acetic acid (5 c.c.) and after the addition of hydrochloric acid (1 gram), a solution of sodium nitrite solution (0.25 gram) was added. When the diazotisation was complete an equal volume of alcohol was added and the mixture heated on the water-bath until all evolution of nitrogen had ceased. The mixture was poured into water the oil which separated was dissolved in ether the e'thereal solution washed with alkali t o remove the phenol dried and evaporated when a small quantity of an oil remained which was not further investigated. The alkaline solution on acidification deposited the phenol as a somewhat viscid red solid.This was collected and purified by crystallisation from hot water whe 2-ACETYLAMINO-3 4-DIMETHOXYBENZOIC ACID ETC. 83 4-cJ~loro-5-~~itroguaiacol was obtained in glistening pale brown leaflets or clusters of prismatic needles which melted a t 161-162O : C7H,0,NC1 requires C1= 17.4 per cent. 0.1236 gave 0.0834 AgCl. C1=17*1. Uiazotisation of 5 6-Dinitro-3-nnzi~zoveratrole 3 4Dinitro-? ; e m trol e (XVI). In the diazotisation of the 5 6-dinitroamineY the conditioris described above for the preparation of 4 5-dinitroveratrole were used. 3 4-Dinitroveratrole separated from alcohol in which it was somewhat sparingly soluble in glistening pa10 yellow prisms melt-ing a t 1 8 1 O : 0.1012 gave 0’1556 CO and 0-0333 H,O. C,H,O,N requires C = 42.1 ; H = 3.5 per cent.A molecular-weight determination carried out by Barger’s method using pyridine as the solvent and benzil as the standard, gave a molecular weight of about 235.8 whereas C,H,O,N requires M.W. = 228. From the diazotisation a small quantity of a phenol was isolated; this was converted into the methyl ether in the usual manner and the methyl ether recrystallised from methyl alcohol when it was obtained in pale yellow leaflets melting at about 88-89O. Unfortunately this substance was not obtained in sufficient! amount for complete purification. C=41.9; H=3*6. A dde tidum. From the difference in behaviour towards alkali of 4 5-dinitro-3-acetylaminoveratrole ( A ) and of ti 6-dinitro-3-acetylamino-veratrole ( B ) i t was considered that the examination of the absorption spectra of these compounds in alcoholic solution and in the presence of alkali might yield interesting results.The alkaline solutions contained five equivalents of potassium hydr-oxide. Mr. J. E. Purvis very kindly examined the absorption spectra and we are greatly indebted to him for the trouble he has taken and for his report which is as follows : “The sources of light were an iron spark and a molybdenum-uranium spark duplicate photographs being ta,ken in each case and the absorption curves drawn. “It will be seen that substance A exhibits one strong band with-out and with the addition of the alkali. The effect of the alkali is to make the band a little narrower and t o cause a considerable shifting of the line of general absorption towards the red end.( ( The neutral solution of the substance 13 shows two fairly well-E 84 GIBSON SIMONSEN AND RAU THE NITRATION OF marked bands whereas the alkaline solution gives only rapid extensions of the line of general absorption. There can scarcely be any doubt that the change in colour brought about by the Oscillation fi-equencies. 2400 2800 3200 3600 4000 4400 4800 3.6 3.2 2.8 2.4 2.2 1.8 1.4 10 Lower curves. I Upper curves. 4 5-Dinitro-3-acetylanzinoverutrole 5 6-Dinitro-3-acetylarninovcrwtrolc (4 I (B)* Neutral solution continuous line. I Neutral solution continuous line. Alkaline solution broken line. Alkaline solution broken line. addition of the alkali has produced a considerable change and it is possible that this may be due to decomposition whereby the vibrations of the original molecule are almost obliterated.“The single band of substance A is not unlike except in posi 2-ACETYLAMINO-3 4-DIMETIXOXYBENZOIC ,4CID ETC. 85 tion the band in the cases of phenol and the clihydroxybenzenes (Hartley T. 1888 53 651; ITartley Dobbie and Lauder T., 1902 81 929; Baly and Ewbaiik T. 1905 87 1347). On the other hand the two bands of the compound 13 are coinparable with the bands of aniline and certain derivatives of aniline for example the anisidines except' again in posit ion (Hartley and Huntington PJjil. TTUUS. 1879 170 I 257 ; Purvis T. 1915, 107 660). '' A consideration of the structure of the two substances indicates a probable sat isfactory explanation of these differences.In the case of substance A where one of the nitro-groups is in the ortho-position with respect to the acetylamino-group the former neutralises the influence of the latter aiid the methoxy-groups can then exert a more powerful influence. This close relationship is not present in the case of substance H where the nearest nitro-group is in the meta-position with respect to the acetylamino-groull. The latter has here more freedom of motion and hence the vibra-tions of the molecule become comparable with those of aniline. " I n the case of the alkaline solution of the substance A the curves indicate t h a t the vibrations are damped b u t t h a t no con-siderable change in the constitution of the substance has taken place. It has been suggested t h a t the solubility of the substance A in alkali may be due to the formation of an unstable salt but this would not largely alter the vibrations for the reason t h a t the influence of the acetyliniino-group would still be locked up by the atljacent :N<:" group. The fact that the absorption spectra of the neutral and the alkaline solutions of the substance A are so similar clearly proves t h a t the not improbable conversion of the nitro-group iii the ortho-position with respect to the acetylamino-/ 0 I\' group into the group N N ~ is not sufficient to effect any funrla-mental change in the inflneuce of the niethoxy-groups." THE CHEMICAL LABORATORY. THE PRESIDENCY COLLEGE, THE UNIVERSITY MADRAS, CAMBRIDGE. SOUTH INDIA. [Received Nozvlnber I7th 191 6.