A NEW TRINITROACETAMINOPHENOL. 1935 CLXXXV1:-A New Trinitroacetaminophenol and its use as a Synthetical Agent. By RAPHAEL MELDOLA, F.R.S. IN the course of some experiments having for their object the preparation of Reverdin's dinitroaminophenol of m. p. 230-231°, referred to in a former paper by one of the authors and F. G. C. Stephens (Trans., 1905, 87, 1206), it was found that the nitration of diacetyl-p-aminophenol (p-acetaminophenyl acetate) gave rise under most conditions to the mononitro-derivative, OAc : NO, : NHAc = 1 : 3 : 4, corresponding to the m-nitro-p-aminophenol of Hiihle (J. p r . Chem., 1891, [ii], 43, 63; see also the recent paper by Reverdin and Bucky, Ber., 1906, 39, 2687). I n attempting to nitrate this mono-1936 MET,DOI,A : A NEW TRTNITROACETAMINOPHENOT, nitrodiacetyl-p-aminophenol so as to obtain the required dinitro- compound, it was found that under certain conditions a trinitro- derivative was produced, and as this compound was found to possess remarkably active properties as a synthetical agent, it has been and is being made the subject of a special investigation.Some of the results so far obtained are made known in the present paper. I n order to prepare the new trinitro-compound, fuming nitric acid is mixed with an equal volume of strong sulphuric acid and the mixture cooled by immersion of the beaker in melting ice. The mono- nitrodiacetyl compound is introduced into the mixed acids in small portions until the solution is nearly saturated, and the trinitro- compound is then precipitated by pouring the acid solution on to ice.The product, after being collected and washed, is best purified by crystallisation from glacial acetic acid. It cry stallises in yellow needles melting with decomposition a t 178-179O." The compound is soluble in boiling alcohol or acetone, and dissolves slightly in boiling water, from which it separates on cooling in slender, yellow needles : 0.0887 gave 14.9 C.C. moist nitrogen a t 15' and 753.8 mm. N= 19.51. 0,1037 ,, 16.9 C.C. 9 1 12' ,, 759.8 mm. N=19-34. C8H,08N, requires N = 19.63 per cent. l t is not absolutely necessary in preparing this compound t o divide the process of nitration into two stages. The trinitro-derivative can also be prepared directly by dissolving diacetyl-paminophenol in the mixture of acids as above.Under these conditions, however, a considerable excess of the acid mixture must be used in order to obtain a good yield. Tho constitution of the trinitro-compound is determined by the following considerations. A mononitro-derivative of the constitution stated can only give rise theoretically t o two possible trinitro-derivatives : OAc OAc OAc (1.1 The first of these formulae represents the compound as the introduction of a third nitro-group into Reverdin's arising from 3 : 5-dinitro- compound and the second (11) as arising by a similar process from 2 : 6-dinitro-pacetaminophenol, that is, as a derivative of isopicramic acid. Experiments have shown that the acetyl derivative of isopicramic acid cannot be further nitrated, whereas the 3 : 5-dinitrodiacetyl com- * All melting points given in this paper were corrected by reference t o standard short-stemmed thermometers having the certificate of the Reichsanstalt, Berlin.AND ITS USE AS A SYNTHETICAL AGENT.1937 pound is quite readily converted by a mixture of nitric and sulphuIic acids into the new trinitro-compound. The orienting influence of the acetoxy-group is paramount in deter- mining the entry of the first nitro-group into position 3, and the joint influence of the nitro- and acetoxy-groups determines the entry of the second nitro-group into position 5 , giving Reverdin’s compound, from which the new trinitro-compound arises. That the acetoxy-group is all important is shown by the now well-known fact that pacetaminophenol itself always gives rise toisopicramicacidonnitration,and the most recent observation by Reverdin and Bucky confirms this in a very striking manner. I n the description of the practical details of nitration given above, it will be noted that the diacetyl-p-aminophenol or its 3-nitro- derivative is introduced directly into the cooled mixture of acids.I n Reverdin and Bucky’s process, the diacetyl compound is first dissolved in strong sulphuric acid, and the solution thus obtained is then treated with the nitric acid mixture, I n these circumstances, as the authors point out, the diacetyl compound undergoes hydrolysis by the sulphuric acid a t the first stage, so that the nitric acid is really acting on p-acet- aminophenol, and the resulting compound is accordingly isopicramic acid (Ber., 1906, 39, 2687).The entry of the third nitro-group in the process now made known appears also to loosen the attachment of the acetyl group as hydrolysis simultaneously takes place and the new compound is accordingly : OH NO,( ’)NO, ,NO, a X H A ~ 2 : 3 : 5-Trinitro-4-acetaminophenol. Properties of the Trinitro-compound.-As might be inferred from its formula, the new compound is strongly phenolic in character. It forms highly-coloured salts of an orange-red colour, but owing to the readiness with which the substance is decomposed by bases, none of these salts could be isolated, nor has it been possible to alkylate or acylate the hydroxyl group. Attempts to remove the acetyl group so as to obtain the trinitroaminophenol also gave only resinous products of decomposition. When sulphuric acid was used as a hydrolysing agent, a small quantity of a crystalline compound was obtained, which on examination proved to be a highly explosive diazo-oxide, resulting no doubt from the simultaneous hydrolybis and diazotisation of the product by one of the nitro-groups removed by the hydrolysing agent, so that in this caw also decomposition takes place.1935 MELDOLA : A NEW TRINITROACETAMINOPHENOL Synthesis of Anhydro-bases.Previous experience with compounds containing a displaceable nitro- group led to the conclusion that in the new trinitroacetaminophenol one of the nitro-groups 2 or 3 would be easily eliminated. It might, for instance, be predicted with certainty that if the corresponding trinitro- p-anisidine could be obtained this compound on diazotisation would lose the 3-nitro-group. The instability of the salts and the ready decomposability of the trinitro-(*ompound in the presence of basic substances distinctly pointed to the conclusion that these properties were due to t b e mobile character of one of the nitro.groups, since polynitro-derivatives of phenols as a rule form stable salts with bases.It therefore seemed probable that under regulated conditions the mobile nitro-group might be replaceable by amine residues giving rise t o compounds of the following types : If, moreover, as seemed most probable, it WRS the 3-nitro-group which was the mobile group, decompositions taking place according to the first of the above schemes might be expected t o give rise to anhydro-bases by the interaction of the ortho-groups.Such com- pounds would be derivatives of substituted benzimiuazole and might be thus formulated * : NO, NR’ Experiments with various amines showed that the new trinitro- compound most readily interacted with primary amines both fatty and aromtttic, but that no action took place under similar conditions with secondary or tertiary bases. The products consisted of anhydro-bases mixed in some instances with the non-anhydridised compound, thus proving that i t is the 3-nitro-group which is replaced. Of the amines thus far tried, positive results have been obtained with ammonia, ethylamine, aniline, a- and /I-napht hylamine, benzy lamine, and piperidine. Negative results were given by dimethylaniline, di- phenylamine, and pyridine. As these iminazoles promise t o be of * I have adopted the numbxing of the atoms in the ring system given in Richter’s ‘‘ Lexikon.”AND ITS USE AS A SYNTHETICAL AOENT.1939 special interest from several points of view, it is proposed to continue their investigation in detail, and the present results are made known as a preliminary contribution to the subject. The compound formed by the action of ammonia, although theoretically the simplest member of the group of substituted iminazoles herein dealt with, will reqiiire further investigation before its constitution can be established. I n all the reactions the nitro-group is probably eliminated in the form of nitrous acid which reacts with the excess of amine with the production of an azo-compound, an alcohol, or simply a salt, according to the nature of the amine.As the compounds described in this paper are all formed by the substitution of various radicles for R' in the N R group in the iminazole ring in the foregoing formula, the constitution will be sufficiently expressed by the systematic name without repeating the formula for each componnd. 4 ; 7 -Din,itro-6-hydroxy-l -phen yl-2-rnethyZbenximinnzole.-The trini tro- compound reacts readily with aniline under all conditions. I n con- centrated alcoholic solution the action is so energetic that spontaneous ebullition takes place, I n order to prepare the above phenpl deriv- ative in quantity the trinitro-compound is dissolved in a considerable excess of alcohol and to the hot solution an excess of aniline is gradually added, A deep orange colour is at once developed, and on cooling the solution deposits the imioazole in ochreous needles After being collected and washed with alcohol and purified by crystallisation from glacial aretic acid, the pure substance crystallises i n transparent, yellow prisms, which become opaque on being washed with alcohol.From alcohol it crystallises in flat, yellow needles. The compound is soluble in all the ordinary organic solvents and is phenolic in character, dissolving in aqueous alkali with an orange colour and being precipitated unchanged by acids. It possesses a feebly basic character, its salts being readily dissociated by water. The melting point is 188-189' : 0.1053 gave 16 C.C. moist nitrogen a t 15O and 753.2 mm. N = 17.63. 0.1007 ,, 15.3 C.C. ,, ?, ,, 16O ,, 765.9 mm.N=17*85. C,,H,o0,N4 requires N = 17.87 per cent. The same compound is also obtained when glacial acetic acid is used as a solvent or when the trinitro-derivative is dissolved in excess of aniline and allowed to stand for some days a t the ordinary temperature. In both these cases aminoazobenzene wits found among the products and was easily separated from the iminazole by taking advantage of the phenolic character of the latter. When aniline acts on the trinitro- compound in alcoholic solution, as in the method oE preparation found most advantageous, there is also formed with the iminazole, which is the main product, a small quantity of another substance which is partly1940 MELDOLA : A NEW TRINITROACETAMINOPHENOL contained in the mother liquor, from which on standing it separates in the form of deep orange prisms.Some of the same compound is easily seen in admixture with the crude iminazole but is removed in the course of purification by crystallisation from acetic acid. This secondary pro- duct is no doubt the non-anhydridised compound, namely, 3 : 6-Dinit~o-2-acetamino-5-hydroxydiplmayZamine : OH This substance is also phenolic and dissolves in alkali with an orange colour. It crystallises from acetic acid in red, prismatic needles melting at 1 7 9 O : N = 16.82. 0.0968 gave 14 C.C. moist nitrogen at 12Oand 744.9 mm. Orily a small quantity of this compound has as yet been isolated and it is proposed to obtain a larger supply for further investigation. 4 : 7-Dinitro-6-hydro~y-1 -benxyZ-8-methylbenximin~zole.-A concen- trated alcoholic solution of the trinitro-compound is mixed with an alcoholic solution of benzylamine containing the latter base in excess, when a reaction at once takes place with the development of sufficient heat to cause ebullition.The solution when cold solidifies to a crystal- line pulp of orange needles. I n order to purify the crude product the crystals were collected, washed with dilute hydrochloric acid and crystallised from alcohol. The orange colour of the deposited crystals immediately disappears on washing with acid, thus indicating that the compound is a benzylamine salt. After treatment with acid and crystal- lisation from alcohol, the pure compound presents the appedrance of flat, silky needles of a greenish-yellow colour.The melting point is 207'. Analysis indicated that in this case the first product is the dinitroacetaminohydroxyphenylbenzylamine : CI,H1206N, requires N = 16.86 per cent. OH /\NO2 N oJ, )NH*CH,C,H~ NH-CO-CH, 0*0886 gave 13.2 C.C. moist nitrogen a t 14" and '763.3 mm. N= 16.29. C,,H1,06N, requires N = 16.22 per cent. This substance is sufficiently basic to dissolve in strong mineral acids, but the salts formed with such acids are dissociated by an excess of water. Ttie compound is also phenolic, dissolving in alkalis with anAND ITS USE AS A SYKTHETICAL AGENT. 1941 orange colour. An attempt to eliminate the acetyl group by boiling the solution of the sodium salt showed that some more complex decom- position takes place with the formation of benzaldehyde.A beautiful, crystalline, ammonium salt consisting of bright orange, prismatic needles is formed by the action of ammonia. When this salt is crystallised from boiling water and then decomposed by treatment with an acid the recovered substance is not the original phenylbenzylamine deriv- ative but the iminazole, so that anhydridisation takes place on boiling the ammonium salt with water. The iminazole is also formed by dissolving the phenylbenzylamine compound in strong sulphuric acid, heating the solution for a few minutes to 100' and then pouring into water. The compound thus obtained crystallises from alcohol in yellow needles melting a t 156' : 0.1048 gave 15.2 C.C. moist nitrogen at 15' and 770.6 mm. N = 17.22. 0.1195 ,, 17.3 C.C. ,, ,, 14' ,, 762 mm. N=17*07.This iminazole is both phenolic and basic. The alkali salts are orange in colour; the ammonium salt is much more soluble than the ammonium salt of the original phenylbenzylamine derivative. The substance dissolves in hydrochloric acid and the solution on the addition of strong acid deposits white needles of the hydrochloride, which are stable only in the presence of excess of acid. 4 : 7-Dinitro-6-hy~roxy-2-methyl-l-ethylbenziminaxoZe.-On adding an alcoholic solution of ethylamiue to the trinitro-compound suspended in alcohol an orange solution is a t once obtained, and this soon solidifies to a crystalline pulp of the ethylamine salt of the trinitroacetamino- phenol. I n order to bring about the iminazole formation, the solution must be heated on the water-bath for some hours.The product is best isolated by collecting the crystalline deposit which separates on cooling, and which consists of the ethylamine salts of the iminazole with some of the ethplamine salt of the phenylethylamine derivative, washing with alcohol, then with dilute hydrochloric acid and finally with water. At this stage the product consists of a mixture of the imin- azole with the non-anhydridised compound and, if the former is required, it is better to ensure complete anhydridisation by dissolving the dry product in a little strong sulphuric acid, heating for a few minutes on the water-bath and then pouring into water. After crystallisation from alcohol the compound consists of orange, nodular crystals melting with decomposition at 2 1 5 O : C15H1205N4 requires N = 17.1 1 per cent.C,,H,2O,N,,HC4 0.1335 gave 23 C.C. moist nitrogen at 13' and 776 mm. This iminazole forms orange salts with alkalis, the ammonium salt N = 20-79. CI,HIoO,N, requires N = 2 1 -09 per cent.1942 MELDOLA : A NEW TRINTTROACETAMINOPHENOL crystallising readily from hot water in bright orange-red needles. The compound is also basic, dissolving in mineral acids with the formation of colourless salts which are stable onlyio presence of excess of acid. 4 : 7-Dinitro-6-hydroxy-1 -a-nup?~thyZ-2-methyl6enximir~azole.--The tri- nitro-compound and a-naphthylamine in excess are heated together in alcoholic solution for some hours on the water-bath, the reaction in this case being less energetic and the yield of iminazole smaller than in the case of the other amines.The whole solation after completion of the reaction is poured into very dilute hydrochloric acid, filtered to remove excess of naphthylamine, the precipitate washed with water, and then extracted with dilute sodium hydroxide and again filtered. The latter treatment separates the iminazole from the a-aminoazo- naphthalene with which it is mixed, the orange alkaline filtrate giving the required compound on acidifying. After crystallisation from alcohol the iminazole was obtained in ochreous, hexagonal tablets melt- ing with decomposition at 241O : 0.0873 gave 11.2 C.C. moist nitrogen a t looand 766.9 mm. N = 15.50. C,,H,,O,N, requires N = 15.42 per cent. No formation of the intermediate a-naphthylphenylamine derivative was observed in this case.4 7-Dinitro- 6-h ydroxy-l -P-naphtA yl-2-methyZ6en ximinaxole.-The re- action in this case is also sluggish and the mode of procedure, both with respect t o the formation of the iminazole and its isolation, was similar to that adopted for the a-naphthylamine compound. I n this case /3-aminoazonaphthalene is also formed together with a certain quantity of the P-naphthylphenylamine derivative. The latter can ba removed by crystallisation of the mixed product from glacial acetic acid after having previously separated the aminoazo-compound by alkaline extraction. From acetic acid the iminazole separates slowly in two forms, brown nodules and ochreous prisms, both forms melting with decomposition at 242' : N = 15.29. 0.1088 gave 13.9 C.C. moist nitrogen at 11' and 763 mm.C,,H,,O,N, requires N = 15.43 per cent. 4 : 7-Dinitro-6-hydroxy -1-rn-nitrophenyl- 2 - methylber~ximinaxole. -In order to prepare this compound the trinitroacetaminophenol is boiled in alcoholic solution with an excess of ni-nitroaniline for a few minutes and the solution then kept gently heated on the water-bath for some hours. The product separates out in yellow needles, which are col- lected, washed with alcohol, and purified by extraction with aqueous alkali and, after filtration of the solution, precipitation by acid. The substance is only sparingly soluble in boiling alcohol and is best purified by repeated crystallisation from glacial acetic acid from whichAND ITS USE AS A SYNTHETICAL AGENT. 1943 it separates in two forms, light, o(*hreous, nodular aggregates of short, Blender needles and brown, nodular aggregates of stumpy needles.Both forms have the same melting point, 242-243O with decomposition : 0*1181 gave 19.3 C.C. moist nitrogen at 13'and 752.6 mm. N = 19.40. The compound is slightly basic and distinctly phenolic in character, the alkali salts dissolving in water with a yellow colour. The silver salt was obtained as an ochreous powder by adding a solution of silver nitrate to a solution of the ammonium salt : C14H,07N, requires N = 19.54 per cent. 0.1369, on ignition, gave 0.0319. Ag = 23.3. C1,H,O7N5Ag requires Ag = 23 15 per cent. Synthesis of Am-conapounds. The trinitro-compound reacts readily with hydrazines, with the formation of hydrazo-compounds which pass by oxidation into azo- compounds. As a typical case the action of phenylhydrazine has been studied and the resulting compound isolated. Its composition and properties indicate that i t is a derivative of hydroxyazobenzene : OH /\NO, NO,~/N,*C,H,. N H* CO*CH, In order to prepare this substance the trinitro-compound is heated with an alcoholic solution containing an excess of phenylhy drazine as long as nitrogen is evolved. On cooling, a crystalline pulp of red needles is obtained. After being collected and washed with alcohol, the substance can be purified by crystallisation from alcohol, from which solvent it separates in red needles decomposing at about 188' : 0*1091 gave 19.4 C.C. moist nitrogen at 14Oand 750 mm. N = 20.33. C14Hl106N5 requires N = 20.63 per cent. This azo-compound is of interest on account of its instability; it is decomposed on boiling with glacial acetic acid and also by alkalis. The compound itself and the products of its decomposition are under- going investigation. During the first part of this research I had the assistance of Nr. F. G. C. Stephens, and during the latter part that of Mr. J. G . Hay, to both of whom I desire to express my thanks. CITY AND GUILDS TECUNICAL COLLEGE, PINSBURY.