940 HINDMARSH KNIGHT AND ROBINSON : LX X IX.-5- Bronaoguaiacol and some Derivatives. By ELLEN MARGARET HINDMARSH ISABEL KNIGHT and ROBERT ROBIN s ON. IN the course of the investigation described in the preceding com-munication i t was found that 5-nitroguaiacol yielded on bromina-tion an ortho- and not as would have been anticipated a para-bromophenol and it was therefore desired to prepare other guaiacol derivatives substituted in the 5-position in order to examine their behaviour on bromination. Cardwell and Robinson (T. 1915 107 255) have already shown that the methoxy-group of acetylguaiacol has a far greater orientating effect than the acetoxy-group and accordingly the bromination of acyl derivatives of guaiacol leads t o the correspond-ing derivatives of 5-bromoguaiacol (I).This phenol behaves normally on further bromination and yields 4 5-dibromo-guaiacol (11). MeO’) MeO/’\Br MeO/\N02 MeO/\NO, HO!,,Br HO!.)Br HO!,)Br H,N?JNH, (1- 1 (11.) (111.) (IV. 1 A mononitro-derivative of the bromoguaiacol could not be isolated and the constitution of the substance is indicated by the fact that the reaction with nitric acid leads t o bromodinitro-guaiacol (IW) and proved by the conversion of the methyl ether of the latter by alcoholic ammonia into 3 5-dinitro-2 4-diamino-anisole (IV). The methyl ether of I11 has a curiously lethargic bromine atom and the action of methyl-alcoholic potassium hydr-oxide on the substance results in the production of a mixture of potassium brorni2e with more potassium nitrite and of a mixture of nitrophenol ethers.NO2 NO ~-RROMOGUAIACOL AND SOME DERIVATIVES. 941 E X P E R I M E N T A L. 5-Brornogicaiacol (I). The acetyl or carbonyl derivative described below (30 grams) was dissolved in alcohol (100 c.c.) mixed with sodium hydroxide (50 grams) dissolved in a little water and the liquid boiled under reflux during thirty minutes. The major part of the alcohol was removed by distillation the residue acidified with hydrochloric acid and the phenol dissolved in ether was finally purified by distillation in a vacuum. The fraction boiling at l5Oo/20 min. constituted nearly the whole of the product and solidified on cool-ing. The substance is readily soluble in most organic solvents, but may be crystallised from light petroleum and is obtained in colourless prisms often of considerable size melting a t 65' : 0.1107 gave 0.1016 AgBr.Br=39*1. C7H70,Br requires Br = 39.4 per cent. This phenol is soluble in aqueous sodium carbonate solution and gives a bluish-green coloration with ferric chloride in alcoholic solution. I t s constitution follows from the conversion of the methyl ether of its dinitro-derivative into a known dinitrodiamino-a nisole . A cetyl Derivati zte (5-Urorn o-2-?rietl~oxyphenyl A ceta &).-2-Methoxyphenyl acetate was readily brominated in chloroform solution by the addition of a molecular proportion of bromine dis-solved in the same solvent. The solution was washed with water, dried with calcium chloride and distilled finally in a vacuum. A large fraction boiled at 164-165"/22 mm.and solidified corn-pletely on cooling ; considerable further quantities of this fraction may be obtained by redistillation of the mixed fractions of lower and higher boiling point. The substance is readily soIuble in alcohol or similar organic solvents and crystallises from light petroleum in leaflets melting at 62-63O: 0.1439 gave 0.1053 AgBr. Br=32.6. C,H,03Br requires Br = 32.7 per cent. 5-Bromo-2-me t hozy ph e rzyl Cctr b onact e .-This derivative was obtained by the addition of bromine (25 grams) dissolved in chloroform (50 c.c.) t o a solution of 2-methoxyphenyl carbonate (20 grams) (so-called guaiacol carbonate) in chloroform (50 c.c.) The bromination occurred with extreme rapidity and the product of the reaction separated in crystals.It was collected and re-crystallised from chloroform and obtained in colourless needles melting at 179-180°. This sparingly soluble substance is dis-tinguished by a remarkable power of crystallisation 942 HINDMARSH KNIGHT AND ROBINSON : 0.1246 gave 0.1081 AgBr. Br=36.9. C,,H,20,Br requires Br = 37.0 per cent. Since 'guaiacol carbonate' is a commercial product and the yield of the bromo-derivative is approximately theoret'ical it is better to prepare 5-bromoguaiacol through the carbonate than through the acetate. 4 5-Dibromoguaiacol (11). 5-Bromoguaiacol dissolved in a little cold acetic acid was gradu-ally treated with a molecular proportion of bromine dissolved in the same solvent. A certain amount of the product crystallised from the solution and the remainder was precipitated on the addition of water.The solid was collected and crystallised from aqueous methyl alcohol and obtained in slender colourless needles melting at 9 5 O : 0.1184 gave 0.1565 AgBr. Br=56.2. C,H,O,Br requires Br = 56.7 per cent. The substance* is freely soluble in an aqueous solution of sodium carbonate and its alcoholic solution becomes intense ivy-green on the addition of ferric chloride. OII methylation with methyl sulphate and potassium hydroxide in the usual manner, 4 5-dibromoveratrole was obtained. The substance was identical with the product of the direct bromination of veratrole but the melting point of 9 2 O was obtained after one crystallisation from alcohol whereas the substance as usually prepared ,requires many crystallisations t o enable i t to reach an equal degree of purity and is evidently contaminated by an isomeride.5-Bromo-4 6-dinitroguaiacol (111). After several unsatisfactory trials the following method was found to result in a high yield of product. Nitric acid (2.5 c.c. D 1-42) mixed with an equal volume of acetic acid was added drop by drop to a solution of 5-bromo-guaiacol (2 grams) in carbon tetrachloride (15 c.c.). The mixture was vigorously shaken during the addition of the acid and the dinitro-derivative separated from the solution and after the addi-tion of water was collected and crystallised from aqueous alcohol. * This compound is possibly identical with the dibromoguaiacol (m. p. 94-95") which Cousin (Ann. Chirn. Phys. 1903 [vii] 29 63) obtained by the direct bromination of guaiacol in chloroform solution although a priori it would have been anticipated that the bromination of the substance would result in 4 6-dibromoguaiacol 943 5-BROMOBTTAIACOL AND SOME DERIVATIVES.The well-defined rhombic prisms melt and decompose a t 182-184O : 0.1372 gave 0.0874 AgBr. Br=27.1. This substance is almost colourless but dissolves in water and alcohol to bright yellow solutions. Its sodium salt is somewhat sparingly soluble and crystallises from water in orange-yellow needles. C,H,O,N,Br requires Br = 27.3 per cent. Like most dinitrophenols the foregoing substance cannot be methylated in aqueous or alcoholic solution and the following method was adopted with excellent results. Bromodinitroguaiacol (15 grams) mixed with potassium carbonate (50 grams) nitrobenzene (75 c.c.) and methyl sulphate (30 grams) was heated in an oil-bath a t the boiling point of the solvent during thirty minutes.The nitrobenzene was removed by distillation in a current of steam and the residual oil easily solidified on cooling. The solid was collected and crystallised from methyl alcohol and obtained in colourless needles melting at 102-103O : 0.1266 gave 0.0780 AgBr. Br=26*2. C,H706N,Br requires Br = 26.1 per cent. I n view of the reactivity of trinitroveratrole towards ammonia and amines i t is surprising that this substance reacts sluggishly even with boiling aqueous-alcoholic ammonia a reagent which rapidly and quantitatively attacks the trinitrcwompound with formation of dinitrodiaminoanisole.When howevcr tho bromo. derivative was heated in a sealed tube a t looo during seven days with a large excess of a mixture of one volume of methyl alcohol with two volumes of concentrated aqueous ammonia a slow con-version into the characteristic red crystals of dinitrodiamino-anisole was observed. The product was collected and washed with boiling alcohol in order to remove unchanged material and then crystallised from nitrobenzene. The flat prisms hzematite-red with blue shimmer melted a t 255O and were identified with 3 5-dinitro-2 4-diaminoanisole * (Nietzki and Kurtenacker Ber., * This substance is readily accessible from trinitroveratrole (Blanksma, Zoc. cit.) and serves to illiistrate the effect of catalysts in the process of acetylation.It may be crystallised unchanged from acetic anhydride and the solution in the hot solvent is intensely coloured. On the addition of a trace of sulphuric acid the colour disappears and the colourless acetyl derivative crystdlises from the solution 944 HINDMARSH KNIGHT AND ROBINSON : 1892 25 282 who give m. p. 250° and Blanksma Proc. K . A k d . Wetensch. Amsterdam 1904 7 462 who gives m. p. 247'). It was thought that the action of amines on the bromodinitro-veratrole might be more rapid than was the corresponding reac-tion with ammonia but this was not markedly the case. The action of methylamine was similar t o that of ammonia and an identical process was employed. The niethylamino-derivative was crystallised from alcohol and obtained in clusters of slender, brownish-red needles melting a t 158-159' : 0.1214 gave 0.1893 CO and 0.0533 H,O.C,H,,O,N requires C = 42.2 ; H = 4.7 per cent. This substance is more readily obtained from trinitroveratrole (5 grams) which was dissolved in hot ethyl alcohol (80 c.c.) and mixed with an aqueous solution of methylamine (20 C.C. of 33 per cent.). After allowing to remain during an hour the solution was boiled under reflux for two hours then cooled and the separated crystals were collected and crystallised from alcohol. The sub-stance so prepared was identified with the product obtained from bromonitroveratrole : 0.8523 distilled with 10 per cent. aqueous potassium hydroxide evolved' NH,Me which neutralisejd 0.243 1 HCl whereas this amount of a substance C9HI2O5N4 yielding 2NH,Me requires 0.2430 HCl.The action of aniline in boiling alcoholic solution on bromo-dinitroveratrole resulted in the production of an orange-red sub-stance which it was thought should be identical with the diphenyl-amine derivative which is obtained from aniline and trinitro-veratrole. This however was not the case and the substance from the bromodinitroveratrole crystallised in red needles which darkened at 245O and did not contain bromine. C=42*5; H=4*9. Dinitroanilino v era trol e, NHPh NO2 M~O/\NO or Meo()No2 * Meo\/NHPh &fed \NO \/ Aniline (5 c.c.) was added to a solution of trinitroveratrole (3 grams) in boiling methyl alcohol (60 c.c.) and the liquid then dlowed t o cool. It was then again raised to the boiling poin ~-BROMOGUAIACOL AND SOME DERIVATIVES.945 and the process twice repeated. The red crystals which separated did not redissolve when the solution was heated. The brilliant red needles were collected and crystallised from alcohol and obtained in needles mixed with a small proportion of compact prisms. The prisms were picked out and appeared t o consist of an isomeride of the main product of the reaction; they have not yet been obtained in sufficient amount for satisfactory exaniina-tion. The needles were recrystallised from acetic acid and then from alcohol and melted at 199O: 0.1183 gave 0.2302 C'O and 0.0451 H,O. The substance is very sparingly soluble in most solvents. C=53.1; H=4*2. C,,H,,O,N requires C = 52.7 ; H = 4.0 per cent. It is evidently t o some extent of acidic character since it yields a red solution with alcoholic potassium hydroxide and may be recovered unchanged on acidification.The solution in nitric acid soon deposits crystals of a higher nitrated derivative which is extremely sparingly soluble and crystallises from much acetic acid in orange-yellow prisms melting and decomposing a t 221O. That this sub-stance is not the expected 2 6-dinitro-3 4-dimethoxydiphenyl-amine is rendered highly probable by the following considerations : (1) Ammonia and. methylamine displace a nitro-group and also a methoxyl when these baseis react with triiiitroveratrole. Aniline on the other hand displaces only the nitroxyl group and the 2 4-dinitrophenyl ether structure is therefore not contained in the product. The failure of aniline to attack a methoxyl group of trinitroveratrole is not due to lack of reactivity of the base, since dinitroanilinoveratrole is also resistant to the action of ammonia.(2) Dinitroanilinoveratrole is comparatively stable towards hot aqueous potassium hydroxide. (3) The substance is not obtained from bromodinitroveratrole by the action of aniline. (4) The existence of two nitro-groups in the ortho-position is indicated by the following experiment Dinitroanilinoveratrole was reduced in alcoholic hydrochloric acid solution by zinc dust, and the coIourless filtered solution a,dded t o a solution of phen-anthraquinone in hot aceltic acid containing sodium acetate. A condensation product was quickly formed and crystallised from the solution in crimson needles. The substance was collected and crystallised from acetic acid and then from ethyl acetate and obtained in flat needles melting a t 222-2250. It is doubtful whether the colour of the substance which might be described as intermediate between mauve and crimson is or is not due t o impurity. The substance is unchanged by boiling dilute hydro 946 ORR ROBINSON AND WILLIAMS : chloric acid and appears to be a true phenanthraphenazine. It dissolves in sulphuric acid to a red solution quickly changing t o brow nish-red . Dinitro-p-t oluidinoveratrol e. This derivative prepared by replacing the aniline in the above by ptoluidine crystallised from alcohol in deep red prisms melb ing a t 1 6 3 O : 0.1302 gave 0.2571 CO and 0-0542 H,O. This substance is sparingly soluble but less so than the aniline C=53*9; H=4*6. C,,H,,O,N requires C = 54.0 ; H = 4.5 per cent. derivative. UNIVERSITY OF SYDNEY. [Received September 4th 1917.