ORIENTATION OF SUBSTITUTED CATECHOL ETHERS. 903 LX XVI I .- Experimmats on the Orien tut i o n qf Substituted Cutechol Ethers. By THOMAS GILBERT HENRY JONES and ROBERT ROBINSON. APPARENT anomalies noted i n the course of attempts to prepare 2-nitrohornoveratrole rendered it necessary to examine the whole question of the entry of substituents into the catechol nucleus and as the matters of interest encountered in the prosecution of the investigation * are of somewhat divergent character they are1 sepa-rately discussed in the ensuing sections. I . Substitution i n Veratrole or Catecho1 Methylene Ether and their Derivatives. ( a ) I n the preparation of monosubstituted catechol ethers only the 4-derivative is obtaineld. F o r example no trace of S-nitrovera-trole is produced in the nitration of veratrole (Cardwell and Robin-son T.1915 107 257) and only the para-compound is obtained o n bromination (see p. 916). ( b ) Disubstituted catechol ethers are 4 5-derivatives. The constitution of 4 5-dinitroveratrole may be definitely proved in several ways of which the simplest depends on the production oE the substance from metahemipinic acid by elimination of the carboxyl groups. The disubstituted catechol ethers are therefore ccniiected with 4 5-dinitroveratrole by transformations and inter-conversions as shown below. A number of known substances of hitherto undetermined constitution are included and in all cases where two specimens are stated ta be identical this was proved by direct comparison and by the determination of the melting point of a mixture.This technique is also implied in the statement that a product was identified with a known compound. There are two well authenticated exceptions to this rule b u t the circumstances in both cases are somewhat unusual. Gaspari (Gaz-zetta 1596 26 ii 231) nitrated bro1noverat)role and obtained a sulost,ance melting a t 1 2 5 O (I). now shown to be 4-bromo-5-nitro verstrole but on brominating nitroveratrole in chloroform solution * The investigations described in this and four of the five following communications were made in the laboratories of the University of Sydney during 1914-1915 and were interrupted before they were quite completed, but as there is no immediate prospect of the possibility of further work in these directions it seems undesirable to delay the publication of the results already ascertained m-Hemipinic acid ORIENTATION OF SUBSTITUTED CATECHOL ETHERS.905 a t looo Cousin (Ann. Chinz. Phys. 1898 [vii] 13 504) produced a n isorneride melting a t 111-112°. The latter reaction has been re-examined and the formatior of the isomeride confirmed although in our experience the main product was a nitrophenol identified as 6-bromo-4-nitroguaiacol (Meldola and Streatfeild T. 1898 73, 681; Rohjertson T. 1908 93 788)) which yielded the bromonitro-veratrole (m. p. 1 1 2 O ) on methylation. The bromiiiation of 4-nitro-veratrcle leads therefore to 6-bromo-4-nitroveratrole. I n this case the reaction proceeds with considerable difficulty a t looo and yet, in view of the tendency to produce 4 5-derivatives i t must be con-ceded that whatever the mechanism here is a genuine example of direction by the nitro-group.A second exception to the rule is found in the synthesis of tetra-liydroberbsrine by Pictet and Gams (Compt. rend. 1911 155 386; Ber. 1911 44 2430)) an anomalous production of a 3 4-disubsti-tuted verztrole apparently due to a particular arrangement in space relative t o the imino-group of the veratrole nucleus in the complicated molecule of which it forms a part. (c) I n the preparation of 3 4 5-derivatives from a 4 5-disubsti-tuted catechol ether the new substituent enters the ortho-position with respect to the more negative of the groups occupying the posi-tions 4 and 5 unless one of these groups is powerfully ortho-direc-tivel.The following are examples which occur in the experimental part of the paper : MeO/\NO + M e 0 / b 2 . McO’ ‘Br Me0 \,Br NO2 ‘\/ (VI. 1 NO, w.1 NO2 NO2 \/ \/ M~O/\,CHO ~ N~O/\CHO M ~ o / \ B ~ MeO/\Br M e O \ l n r ; MeOI INe -3 MeOl /Me Med, Me mv.1 It appears t o be generally recognised that the1 orienhating effect of a positive group such as methoxyl is overwhelmingly greater than t h a t of a negative group such as nitroxyl and t h a t the influence of negative groups is chiefly felt in diminishing the positive un-saturation of the molecule and so inhibiting further substitutions which owe their occurrence to the reactivity associated with th 906 JONES AND ROBINSON EXPEBIMENTS ON THE unsaturation of the nucleus conjugated (comparo this vol.p. 964) with that of t-he positive centres. When two identical positive groups co-exist in the same inolecule and direct substitution t o different positions a means is provided for the examination of the effect of negative groups on their orientating power. The following examples illustrate the weakening effect of a negative group on a positive centre situated in the ortho-position and those which are cited zbove are probably due to a similar effect exerted froin the para-Fosition. CHO CHO ; Perkin Roberts and Robinson (T. 1914 106 2389). \/ NO2 NO2 \/ (XII.) ONe OMe OMe MeO'\ MeO/\No2 (see page 912). Med I Me"[ I \/ NHAc NHAc /\No ; Blanksma (Bee. t m v . Chiin. 1907 27 49). /\ I t --+ \/ OEt OEt The exceptional behaviour of o-veratric acid on nitration (Cain and Simonsen T.1914 105 159) has already been adequately dis-cussed by Gibson Simonsen and Rau (this vol. p. 73). 11. The Infiucnce of u ,Tegative Groiip~ 011 CI Positive Group in t h e illeta-position. Perhaps the most widely known example of this effect is to be found in connexion with diazo-coupling with a-naphthylamine and a-naphthol and uith their sulphonic acids. The arrows show the position taken up by the entering azo-group ORIENTATION OF SUBSTITUTED CATECHOL ETHERS. 907 Comparable with this is the behaviour of ace(t.ylguaiaco1 and of acetylvsnillin on nitration (Pschorr and Sumuleanu Ber. 1899, 32 -3405) : .1 Me0 '\ MeO/\CHO AcU\)+ AcUi\, We have obsened another example of the same that the bromination of 5-nitroguaiacol (see p.6-bromo-5-nitroguaiacol : Me kind and find 91 7) produce,s Me (11.) (111.) I n all these cases an ortho-position is preferred t o the para and i t would seem t h a t a negative group in the meta-position to the directiJe positive group is responsible f o r the effect. There is evi-dence too that it is not merely an ortho-substitution which is favoured but that it is the particular ortho-position situated between the positive and negative groups. Thus Kauflar and Wenzel (Ber. 1901 34 2239) observed that 2-nitro-p-tolyl methyl ether (11) gave 2 3-dinitro-p-tolyl methyl ether (111) on nitration, and there are many similar cases which have been recorded. It must further be pointed out that a positive group in the ortho-position has precisely the opposite effect to the meta-situated nega-tive group.An example of this is found above in I (a) or in com-paring the nitration of aceitylvanillin with that of veratraldehyde. In the former ca,se (see above) the nitro-group enters the ortho-posi-tion with respect t o the methoxy-group whilst in the latter i t enters the pra-position and 6-nitroveratraldehyde is p7oduced. It is possible t o translate all observations on orientation and cognate problems i n t o the form of expressions which represent the distribu-tion of affinity and the nature of the partly dissociated simple o r conjugated unsaturated systems t o which the initial additions occur. The more precise presentation of the difficulties which is so obtained is to some extent helpful but especially in connexion with the effect of group on group the experimental data cannot yet be regarded as sufficient t o enable very definite conclusions t o be drawn.This is perhaps partly due t o the circumstance t h a t the entry of a pronouncedly negative or positive group affects the state of saturation of all the atonis in the molecule and the difficulty N N 908 JONES AND ROBlNSON EXPERIMENTS ON THE resembles that which is met in attempting t o trace a relation between constitution and physical properties. 111. The flitration of Eromopiperonal. Oelker (Ber. 1891 24 2593) studield this reaction and stated t h a t the products were bromonitropiperonal melting a t 8 9 O and bromodinitropiperonal melting a t 172O. These substances are, however bromonitrocatechol methylene ether (IV) and Eromodi-nitrocstechol methylene ether (V) the aldehydo-group having been eliminated.The latter substance on reduction yields 3 4-diamino-catechol methylene ether isolated in the form of a phenanthra-phenazine but under the same conditions of reduction the corse-sponding veratrole derivative (VI) retains its bromine and yields a bromodiaminoveratrole. I V . The Action of Xitric Acid on iti etl~ylenediosyisatil?. Herz (Ber. 1905 38 2857) prepared methyleuedioxyisatin by the moderated oxidation with nitric acid of the readily accessible dimethylenetetraoxyindigotin and represented the further action of nitric acid as resulting in the formation of an acid (VII) which, when heated with aqueous sodium carbonatel lost carbon dioxide with the formation of the nitroamine (VIII) : NIT Them transformations NO, (VII.) NO2 (VIII. ) must however be represented in the fol-lowing manner since we have identified the product as 5-nitro-4-aminocatechol methylene ether and find that its production is accompanied by that of sodiuni oxalate. Moreover Herz points out that the analytical data f o r V I I agree with the formula C,H,O,N almost as well as for C,H,O,N, ORIENTATION OF STJBSTITUTED CATECHOL ETHERS. 909 V. A R m c t i o n of Piperonylic Acid. Mr. J. W. Hogarth discovered in 1914 that a crystalline sub-stance melting a t 86O is obtained by the action of bromine on a solution of piperonylic acid in aqueous sodium carbonate and the further investigation of this compound showed that it is 4 5-di-bromocatechol methylene ether (IX) and that i t is obtained in quantitative amount.From the conditions requisite f o r its formation (see p. 913j, the conclusion may be drawn that the displacement of the carboxyl group is the first reaction and that the monobromo-derivative is then further brominated. I n all probability the latter stage is rapid in coinparison with the former. This view is confirmed by the formation of 6-bromohomoveratrole (see p. 920) by the application of a similar process t o 4:5-diinethoxy-o-toluic acid and the reaction is evidently of the same character as that by means of which bromostyrene may be obtained from cinnamic acid. Such displacements are clearly analogous to sub-stitutions and are certainly preceded by addition whilst the group displaced may be removed by hydrolysis which is facilitated by much the same conditions that determine the separation of the acetyl group in the preparation of chloroform from acetone.If the following formulze are compared it will be seen that there are three factors which should render a group *CO-R in a hypo-thetical additive product such as X readily removable by hydro-lysis namely the bromine atom in the a-position and the two double bonds in the ring. Cl,C-/-COMe NO,!*CH,- -C02H Me I c /\ 0 CH,-j-CO,FI I Br(OH) (X* 1 The formation of dibromocatechol methylene ether may be employed as a sensitive test €or piperonylic acid since the colour developed in the sulphuric acid solution of the substance by the addition of a trace of nitric acid is highly characteristic.It is N N* 910 JONES AND ROBINSON EXPERIMENTS ON THE also probable that the method will be useful in the investigation of acids derived from the alkaloids in degradation experiments, and Professor W. H. Perkin has already found such an oppor-tunity in connexion with a methylpiperonylic acid obtained from cryptopine (T. 1916 109 918). VI. Fh e n n t h m ph e 12 c( z iu e D I 1’ i vo ti 2’ e s . It has been found to be a general rule that the ethers of 1 2-dihydroxyphenanthraphenazine are bright yellow and exhibit green fluorescence in benzene or other neutral solvent whilst the ethers of 2 3-dihydroxyphenanthraphenazine are faintly yellow and yield almost colourless solutions with intense violet fluores-cence.The latter property can be made the basis of perhaps the simplest method of obtaining an indication that a plant product is a derivative of veratrole substituted only in the 4- or 4:5-positions. A small quantity of the substance is boiled with 40 per cent. nitric acid in such a manner as to ensure vigorous oxida-tion and concentration of the solution; a further quantity of con-centrated nitric acid is then added and the boiling continued for a few minutes. The mixture is added to water and extracted with ether the extract washed with water and evaporated and the residue however small dissolved in a little alcohol and after the addition of two o r three drops of hydrochloric acid reduced by zinc dust. The filtered solution is mixed with sodium acetate and a solution of a few crystals of plienanthraquinone in hot aqueous sodium hydrogen sulphite and after boiling is extracted with benzene.The benzene is clarified by means of calcium chloride and filtered and the fluorescence observed. The reaction may be applied with even more certainty to the products obtained by oxidation with an alkaline solution of potassium permanganate of the substance which is under investigation. Positive results were obtained using about 0.05 gram of papaverine trimethyl-brazilin eudesmin and several synthetical compounds which hap-pened to be in the laboratory a t the time the experiments were made. The preparation of 1 2 4-trimethoxyphenanthraphenazine and of the isomeric pyrogallol derivative (see p. 928) confirms the correctness of the constitution assigned by Blanksma (Proc.K . Akad. W e t e n s c h . A m s t e r d a m 1904 7 462) t o the dinitrotrimeth-oxybenzene (m. p. 152O) which he obtained by the action of methyl-alcoholic potassium hydroxide on trinitroveratrole. VII. A N e w Z e t e r o c y c l i c iVuclezis. On attempting to reduce 4 5-dinitroveratrole to a nitroamine by means of hydrogen sulphide and ammonia an unusual resul ORIENTATION OF SUBSTITUTED CATECHOL ETHERS. 91 1 was obtained and the product was a sparingly soluble orange-yellow crystalline compound C,,HiGO,N,S which on reduction furnished a base C,GH,,O,N,S having the properties of a deriv-ative of veratrylamine (see p. 925). Evidently a nitro-compound has been reduced t o the corresponding amine.Bearing in mind the method of formation of the substance C,,H,,O,NIS it seems that the fragments to be combined are Me0 ’\-N N/\OJfe I NO,) IOMa’ l\ltO\/-N ’ \/ and it then appears that the formula of the substance must be one of the following: (XII.) \ _._I____ w--(improbable) There is no evidence which enables a decisive choice t o be made from the various possibilities but perhaps XI is preferable as being analogous t o the constitution now accepted for benzfurazan oxide (XII) (Green and Rowe T. 1913 103 897; Forster and Barker ibid. 1918). The whole questioii of the mode of forma-tion and the properties of these substances will be more closely investigated when opportunity occurs. I n the meantime the SN, group has been provisionally designated ‘‘ thiotriazo,” and the substance XI is described as 6-nitroveratryl-4 5-thiotriazo-veratrole.E x P E H I M E N T A I,. 3 4-Binitmveratrole (XIII). 3-Nitroveratrole was dissolved in cold nitric acid (D 1.42) and the solution allowed to remain during two hours and then poure 912 JONES AND ROBINSON EXPERIMENTS ON THE into water. The precipitated oil soon solidified and the sub-stance was purified by several crystallisations from methyl alcohol. The pale yellow needles melted at 9Go with previous softening, and although obviously not quite pure the amount of material available was insufficient to enable us to remedy this by a long series of fractional crystallisations : 0.1095 gave 0.1699 CO and 0.0372 H,O. C,H,O,N requires C =42-1; H = 3.5 per cent.The substance is readily soluble in most organic solvents and is changed by fuming nitric acid to 3 4 5-trinitroveratrole. Gibson, Simonsen and Rau (this vol. 83) have described as 3:4-dinitro-veratrole a substance melting at 1 8 1 O which is sparingly soluble in alcohol. I n the introduction to their communication these authors recognise the improbability that 3 4-dinitroveratrole can have so high a melting point but since the molecular weight of the substance was determined they do not reconsider the view advanced. When opportunity offers attempts will be made t o prepare the dinitro-derivative by a new method and so clear up the question of the melting point. In the meantime the follow-ing experiment proves the constitution of the substance obtained as described above.The substance (0.5 gram) was dissolved in boiling alcohol (10 c.c.) mixed with concentrated hydrochloric acid (5 c.c.) and an excess of zinc dust added in one portion. After the stormy reaction water was added and the solution filtered mixed with excess of sodium acetate and with a solution of phenanthraquinone in hot aqueous sodium hydrogen sulphite to which sodium acetate had also been added. The mixture was boiled and the quin-oxaline derivative soon separated in yellow flocks which were collected dried and crystallised froni alcohol and so obtained in long yellow needles melting sharply at 175O. Pisovschi (Ber., 1910 43 2137) has previously prepared this 1 2-dimethoxy-phenanthraphenazine and the product from 3 4-dinitroveratrole agrees in every respect with his description.Like the correspond-ing methylenedioxy-derivative (compare p. 927) its benzene soln-tion exhibits intense green fluorescence. C=42*3; H=3*8. B ~ ~ O / \ N H A ~ \/ MeOI IBr ' 6-Bromoace t o ucra t rylamide, Acetoveratrylamide was brominated in cold acetic acid solution by means of a molecular proportion of bromine. The reaction was almost instantaneous and after the addition of water th ORIESTATION OE’ SUBSTITUTED CATECHOL ETHERS. 9 13 substance was collected and crystallised from methyl alcohol. From a fairly dilute solution a single stellar aggregate of needles, some of them 9 cni. long was obtained. The melting point was 140° : 0.1332 gave 0.0912 AgBr. Br=29*1. This substance was converted into 4 5-dibromoveratrole in the following manner.The amide (10 grams) was boiled during ten minutes with saturated aqueous hydrobromic acid (25 c.c.) then diluted with water (150 c.c.) cooled t o -5O and the amine con-tained in the solution diazotised in the usual way. Copper powder was then added and after remaining overnight the reaction was completed by heating on the steam-bath and the whole extracted with ether. The solution was washed with alkali and water, dried and evaporated and the residual oil gradually crystallised on keeping in the ice-chest. It was freed from impurity by con-tact with porous porcelain and after crystallisation from alcohol, was obtained in prisms melting a t 92-93O identical with the product of bromination of veratrole. C,,H,,03NBr requires Br = 29.2 per cent.4 5-ljihroniocc-ctec?iol Methyle?te Ether (IX). This compound is readily obtained by adding bromine water t o a solution of piperonylic acid in aqueous sodium carbonate until no further precipitate is formed. It may be crystallised from alcohol and is so obtained in colourless glistening leaflets melt-ing a t 86O and moderately readily soluble in most organic solvents : 0.1276 gave 0.1703 AgBr. Br=56.8. The pale yellow solution in sulphuric acid is changed to crimson on the addition of a trace of nitric acid. The substance is not formed by treatment of an alkaline solu-tion of piperonylic acid with ready-formed hypobromite or even by the bromination of piperonylic acid in acetic acid solution. Neither can i t be obtained by the addition of bromine wahr t o a solution of bromopiperonylic acid in sodium carbonate.Veratric acid did not undergo the reaction so readily as piperonylic acid, but the result was similar and 4 5-dibromoveratrole was isolated. It seems probable that the method will be useful in the investiga-tion of carboxylic acids derived from alkaloids and other natural products by oxidation. 4 5-Dibromocatechol (Cousin Zoc. cit. 487) which yields 4 5-dibromoveratrole on methylation was converted by methylene C,H,O,Br requires Br = 57.2 per cent-914 JONES AND ROBINSON EXPERIMENTS ON THE iodide and &odium ethoxide in b d i n g alcoholic solution into 4 5-dibromocatechol methylene ether melting a t 86* and identical with the substance obtained as described above.This compound was also produced by the direct bromination of catechol methylene ether in acetic acid solution. 6-Nit rou erat r y lamin e (XIV) 6-Nitroacetoveratrylamide was boiled with concentrated hydre chloric acid until the whole of the yellow needles passed into solution. The pale yellow hydrochloride of the base separated on cooling and on the addition of much water was decomposed yield-ing the orange nitroamine. This was collected and crystallised from alcohol from which it separated in deep orange prisms melt-ing a t 175O: 0.1304 gave 0.2315 CO and 0*0600 H,O. C8H,,0,N requires C = 48.5 ; H = 5.0 per cent. The substance could be diazotised and gave a crimson azo-compound by coupling with P-naphthol. When the diazonium bromide prepared in hydrobromic acid solution was treated with copper powder nitrogen was evolved and after completing the reaction by gentle heating the neutral substance formed was isolated and identified with 4-bromo-5-nitroveratrole melting at 125O.A cetyl Derivative.-Acetoveratrylamide (10 grams) in acetic acid (50 c.c.) was nitrated in the cold by the addition of nitric acid (10 c.c. D 1.42) in acetic acid (50 c.c.). The bright yellow product of the reaction separated for the most part in the crystal-line condition and after the addition of water was collected and recrystallised from alcohol in which the substance is somewhat 'sparingly soluble. It was obtained in long needles melting a t C=48*4; H=5*1. _ . 1990 : 0.1258 gave 0.2326 CO and 0.0592 H,O. C=50*4; H=5*2.C,,H,,0,N2 requires @= 50.0 ; H = 5.0 per cent,. 5-Nitro-4-a ce t ylaminoca t e c h ol M e thylene Et It er, This derivative is obtained in theoretical amount when 4-acetyl-arninocatwhol methylene ether is nitrated in cold acetic acid solu-tion. After the addition of water the substance was collected and crystallised from acetic acid and then from ethyl acetate ORIENTATION OF SUBSTITUTED CATECHOL ETHERS. 915 The bright yellow needles melt at 209O and the compound is sparingly soluble in boiling alcohol : 0.1247 gave 0.2207 CO and 0.0419 H,O. C,H,O,N requires C=48*2; H =3.6 per cent. I n view of the results of Herz (Zoc. cif.) which are discussed 011 p. 908 i t is interesting t o note that this amide is readily hydrolysed by alkaline agents and even by a boiling solution of sodium carbonate but the more convenient method is to employ hydrochloric acid diluted with half its volume of alcohol.The acetyl derivative is finely powdered and treated with the boiling mixture until a homogeneous solution is obtained. On the addi-tion of water an orange crystalline precipitate of pure 5-nitro-4-aminocatechol methylenc ether separates and after crystallisa-tion from benzene the substance melts a t 1 9 8 O and is identical with the compound obtained by Herz and also by Mameli (Gazzetta 1909 39 ii 172) by the action of alcoholic ammonia on 4 5-dinitrocatechol methylene ether. The amine is most easily obtained by a modification of Herds process starting with nitro-piperonal. The nitroaldehyde (80 grams) dissolved in 'acetone (240 c.c.) was heated on the steam-bath during half an hour with aqueous N-potassium hydroxide (750 c.c.).The paste of the indigotin derivative was collected and washed and gradually added with stirring to nitric acid (150 c.c. D 1.42) and water (100 c.c.). The oxidation may be induced at first by gentle warm-ing after which the further application of heat is disadvantageous. The product was collected and washed with water and then boiled during five minutes with a solution of sodium carbonate (50 grams) in water (500 c.c.). The nitroamine was precipitated in the crystallised condition and was separated and purified by solu-tion in concentrated hydrochloric acid and recovery by dilution with water. 5-Nitro-4-aminocatechol methylene ether may be recovered unchanged after being boi! 3d with acetic anhydride but in the presence of a trace of sulphuric acid the acetylatioll is rapid and the derivative crystallises from the solution.The nitro-amine is attacked by hot aqueous sodium hydroxide alld a blood-red solution is produced but the reaction is complex and u11-accompanied by evolution of ammonia. C z 4 8 . 3 ; H=3*7 916 JONES AND ROBINSON EXPERIMENTS ON THE 5-Nitro-4-acetylaminocatecliol methyleiie ether (1 gram) was reduced during an hour by heating on the steam-bath with acetic acid (25 c.c.) stannous chloride (0.5 gram) and excess of tin. After o'ie or two minutes a tin compound separated from the solu-tion in colourless crystals but this gradually disappeared and at the end of the operation the liquid had a pale yellow colour.Water and sodium hydroxide sufficient to redissolve the precipi-tate were added and the solution was twice extracted with ether. The combined extracts were dried with potassium carbonate and evaporated and the crystalline residue purified by several re-crystallisations from benzene. The colourless transparent leaflets so obtained appear t o contain solvent of crystallisation and became opaque on exposure to the air. The substance was dried a t looo: C=61*0; H=4*6. 0.1113 gave 0.2490 CO and 0.0463 H20. C9H,02N requires C = 61 -3 ; H = 4.5 per cent. This base is sparingly soluble in ether benzene or light petroleum but dissolves freely in methyl alcohol and also t o some extent in hot water from which it crystallises in needles. It melts a t 226-227O after sintering a t 223O.The hydrochloride is readily soluble in water but' may be precipitated in needles by saturation of the solution with salt. The hydrogm oxalate is sparingly soluble and crystallises from water in characteristic satiny plates. The p'crate crystallises from methyl alcohol in canary-yellow clusters of long needles. It is sparingly soluble and carbonises between 230° and 250° without sudden decomposition. 4-Bromo-5 6-ditaitrovcratroZe (VI). A quantitative yield of 4-bromo-5-nitroveratrole is obtained by the nitration of bromoveratrole in acetic acid solution (compare Gaspari Zoc. cit.) and on fractionally crystallising the product it was found to be perfectly homogeneous and consequentJy the bromoveratrole is also homogeneous and contains no 3-bromo-veratrole.4-Bromo-5-nitroveratrole may also be obtained by the action of nitric acid (U 1-42) on that bromoveratric acid which results from the hydrolysis of brominated methyl veratrate or from the oxidation of bromoveratraldehyde. Gaspari (Zoc. cit.) obtaine ORIENTATION OF SUBSTITUTED CATECHOL ETHERS. 91 7 the dinitro-derivative by the action of fuming nitric acid on bromoveratrole but from the point of view of yield i t is better to isolate the bromomononitroveratrole and submit this substance t o the action of cold fuming nitric acid (U 1-52) I n this way the amount obtained approximates closely to that demanded by theory. The constitution of this substaiice is proved by its coii-version into a broinodiniethoxyphenanthraphenazine as described on p.928. Br 5-Nitroguaiacol (5 grams) dissolved in acetic acid (50 c.c.) was brominated by the gradual addition of bromine (5 grams) dis-solved in acetic acid (20 c.~.). After half an hour the mixture was diluted with water and the solid collected and recrystallised from aqueous alcohol. The substance is obtained in pale yellow needles which become prisms if allowed to remain in contact with the solvent and in either crystalline condition melts at 1 5 0 O : 0.1364 (0.1206) gave 0.1032 (0.0913) AgBr. The substance is readily soluble in aqueous sodium carbonate Br = 32.2 (32'2). C,H,O,NBr requires Br = 32.3 per cent. t o a red solution. The foregoing bromonitroguaiacol was methylated by shaking its warm solutior in aqueous sodium hydroxide with methyl sulphate.The pale yellow substance was collected and crystal-lised from alcohol. The slender needles melted a t 81-82" and when mixed with specimens of 5 4- and 6 4-bromonitroveratroles the melting point was depressed: 0.1175 gave 0.0840 AgBr. Br=30.4. C,H,O,NBr requires Br = 30.5 per cent: This substance is rather readily soluble in organic solvents and dissolves in sulphuric acid t o a bright red solution from which i t may be recovered unchanged on the addition of water Bromiization of 4-ll'itroveratrole. Formation of 6-Bromo-4-nitrogunia col and of 6-Bro rn 0-4-12 it rov era t rol e . 4-Nitroveratrole (10 grams) chloroform (20 c.c.) and bromine (9 grams) were heated together during forty-eight hours in 918 JONES AND ROBINSON EXPERIMENTS ON THE sealed tube placed in boiling water.After the reaction ether was added and the solution shaken with concentrated aqueous sodium hydroxide. The precipitated sodium salt was collected, washed with ether dissolved in water and acidified with hydro-chloric acid. The separated nitrophenol was collected and crystal-lised from alcohol and again from benzene and obtained in pale yellow glistening needles which melted at 150-152O with some decomposition and was identified with 6-bromo-4-nitroguaiaco1, which Meldola snd Streatfeild (Zoc. cit.) obtained by the bromina-tion of 4-nitroguaiacol and which was also prepared by Robertson (Zoc. cit.) by nitrating o-bromoguaiacol. The melting points assigned to the substance by these authors are respectively 1 4 2 O and 1 4 8 O .The ethereal solution from the separation of the sodium salt was well washed with water dried and evaporated. The residue was fractionally crystallised at first from methyl alcohol and later from ethyl alcohol and separated into unchanged nitroveratrole and a small proportion of the more sparingly soluble 6-broms4-nitroveratrole which crystallised in slender needles melting a t The substance is more readily obtained by methylating 6-bromo-4-nitroguaiacol by means of methyl sulphate in the usual manner. 11 2-1 13'. 4-Bro m o-5-ni t r o ca t e chol Me t h y 1 en e E t her (IV) . This substance has been prepared by Oertly and Pictet (Ber., 1910 43 1336) by the action of nitric acid on bromopiperonylic acid and an identical compound is obtained by the nitration of an acetic acid solution of bromocatechol methylene ether pro-duced in its turn by the bromination of catechol inethylene ether dissolved in acetic acid by means of bromine vapour (from 1.2 mols.of bromine) diluted with air. Another method of preparation depends on the displacement of the amino-group of 5-nitro-4-aminocatechol methylene ether by bromine by means of the diazo-reaction. The amine was dissolved in concentrated aqueous hydrobromic acid and diazotised by the addition of sodiuni nitrite until a clear solution was obtained on treating a test portion with water. The solution was diluted, treated with copper powder and allowed t o remain overnight and then extracted with ether. The bromoiiitrocatechol methylene ether which passed into the ether was obtained by evaporation of the solvent and crystallisation of the residue from alcohol.The pale yellow needles melted a t 89O and the substance was identical with the compounds obtained by the other methods here describe ORIENTATION O F SUBSTITUTED CATECHOL ETHERS. 919 The most cmvenient process for the production of this substance is however the nitration of bromopiperonal. The reaction proceeds in acetic acid solution but it is better to add the aldehyde (15 grams) gradually to nitric acid (100 c.c., D 1-42) during an hour with careful cooling. The product partly crystallises from the solution and after the addition of water, may be collected and crystallised from alcohol. The yield of pure bromonitrocatechol methylene ether melting a t 89O and quite identical with the substance obtained as described above is very good and there can be no doubt that this is the substance which Oelker (Zoc.cit.) recorded as a bromonitropiperonal. 'The follow-ing analyses were made of this nitration product of bromo-piperonal : 0.1312 gave 0.1657 CO and 0.0237 H,O. 0.1306 , 0.0983 AgBr. Br=32*1. C=34*4; H=2.0. C7H,0,NBr requires C = 34.2 ; H'= 1.6 ; Br = 32.5 per cent. 4-Bronz.0-5 6-dinit TO ca t e c hol Met h y Zene Ether. This derivative may be obtained directly from bromopiperonal or better from bromonitrocatechol methylene ether by dissolving either in an excess of cold nitric acid (D 1.52). The sparingly soluble substance crystallises from ethyl alcohol in pale yellow, prismatic needles melting at 1 7 2 O which is the melting point assigned by Oelker (Zoc.cit.) t o his supposed bromodinitro-piperonal : 0.1437 gave 0.1534 CO and 0.0153 H,O. 0.1527 , 0.0982 AgBr. Br=27*4. C=29*1; I3=1*2. C7H,0,N,Br requires C = 28.9 ; H = 1.0 ; Br = 27.5 per cent. 6-Bromo-5-n it ro homo u e m t rol e (XV) . Bromine (7 c.c.) dissolved in acetic acid (50 c.c.) was added to a mixture sf hornoveratrole (20 grams) and acetic acid (10 c.c.). Rise of temperature was checked during the addition and the halogen was rapidly absorbed and the product isolated in the usual manner. 6-Bromohomoveratrole is an oil with a pleasant aromatic odour and boils a t 267O: 0.1422 gave 0.1153 AgBr. Br=34.5. C,H,,O,Br requires Br = 34.6 per cent. Attempts were made to bring this substance into reaction with magnesium in order to facilitate the synthesis of m-hemipinic acid, but without success.The bromo-derivative (20 grams) in acetic anhydride (40 c.c. 920 JONES AND ROBINSON EXPERIMENTS ON THE was cooled in ice water and a previously prepared well-cooled mixture of nitric acid (15 c.c D 1.42) and acetic anhydride (40 c.c.) gradually added. After half an hour the reaction mix-ture was poured into water and the precipitated oil washed with several changes of dilute aqueous sodium hydroxide. The oil soon solidified and was collected and crystallised from methyl alcohol, from which it separated in long pale yellow needles melting at 1210 : 0.1520 gave 0.1029 AgBr. Br=28*8. C,H,,O,NBr requires Br = 29.0 per cent. The constitution of this substance is deduced in the following manner.Bromohomoveratrole is oxidised by warm alkaline potassium permanganate solution to 6-bromoveratric acid which, however was not identified as such but was converted by nitric acid into 4-bromo-5-nitroveratrole. The bromination product of homoveratrole is therefore 6-bromohomoveratrole and the nitro-group in the derivative must occupy either the position 5 or 2. That the substance is not an o-nitrotoluene is shown by the fact that i t does not contain an activated methyl group and for ex-ample will not condense with cotarnine in alcoholic solution in the presence of sodium ethoxide. I n connexion with another investigation one of us has recently prepared 2-nitroh~moveratrole, and this may be converted into an anhydrocotarnine derivative.Moreover since the introduction of halogens usually increases the facility with which such condensations are effected it seems that the bromonitrohomoveratrole must have the constitution here assigned to it. The formation of this substance was utilised in order to show that the action of bromine on a solution of 4:5-di-methoxy-o-toluic acid (Perkin and Weizmann T. 1906 99 1651) in aqueous sodium carbonate leads to the quantitative formation of 6-bromohomoveratrole. The authors are greatly indebted to Pirofessor W. H. Perkin for the provision of a specimen of the acid in question. NO, Me@/\CHO 6-Br omo-2-nit ro v era t ra Id ’- - - -’ - enycce M~o!,,)B~ 6-Bromoveratraldehyde was nitrated by slowly adding the powdered substance to ten times its weight of nitric acid (D 1*42), checking undue rise of temperature by cooling in water and when the solid had passed into solution the mixture was allowed t o remain during half an hour and then poured into water.The precipitate was collected and dissolved as far as possible in ORIENTATION OF SUBSTITUTED CATECHOL ETHERS. 921 solution of sodium hydrogen d p h i t e . The residue was crystal-lised from alcohol and the pale yellow needles were identified as 4-bronio-5-nitroveratrole melting at 124O. The amount of this substance which was obtained was relatively small. The hydrogen sulphite solution was decomposed by the addition of sodium carbonate and the precipitated aldehyde collected and crystallised from alcohol. The very pale yellow needles melted at l o g o : 0.1259 gave 0.0809 AgBr.Br=27'3. The constitution of this substance is demonstrated by the farma-C9H805NBr requires Br = 27.6 per cent. tion of the indigotin derivative described in the next section. 4 41-Uibromo-6 ; 7 6' 7t-tetmmet~oxyi,znigotilz, Br Br oco->c:c<,,l -GO/\ lo& \/ OMe Meo\/NH OA90 The bromonitroveratraldehyde (4 grams) was dissolved in acetone (30 c.c.) and aqueous potassium hydroxide (5 C.C. of 10 per cent.) added. After a minute the mixture was diluted with water (100 c.c.) and boiled during five minutes. The precipitated indigotin was collected and washed with hot alcohol dried and crystallised from nitrobenzene : 0.1281 gave 0.0890 AgBr. Br=29*6. CmHl,06N,Br requires Br = 39.6 per cent.The substance is obtained iii slender needles which have a par-ticularly brilliant coppery lustre and do not melt a t 360° but at about this temperature begin to carbonise. It is extremely sparingly soluble in solvents and its dilute solutions in boiling nitrobenzene and aniline are pure blue. The purple solution in sulphuric acid quickly becomes blue. 5-Bromovera traldehyde. This substance has been previously prepared by Dakin (Amer. Chem. J. 1909 42 494) by the methylation of 5-bromovanillin with methyl sulphate and potassium hydroxide and also by Pschorr Selle Koch Stoof and Treidel (Aunaleiz 1912 391 31) by a similar process applied t o the product of bromination of protocatechualdehyde but these authors give no details of the process employed.Our experiences in this connexion indicate a precaution which it is desirable to take in methylating phenolic aldehydes 922 JONES AND ROBINSON EXPERIMENTS ON THE Vanillin was brominated in acetic acid by means of rather more than a molecular proportion of bromine and the bromo-aldehyde was then methylated by methyl sulphate and potassium hydroxide in alcoholic solution. The operation was not entirely satisfactory owing to the readiness with which the aldehyde under-goes thO Cannizzaro reaction and no more than a 50 per cent. yield could be obtained. The conditions were similar to those which gave good results in the preparation of veratraldehyde (Perkin and Robinson T. 1907 91 1079) but' for the reason mentioned the solution should never be allowed t o become very strongly alkaline.On the addition of water an oil separated and usually slowly crystallised when the mixture was kept in a cold place. Occasionally however the oil could not be solidified and was dissolved in ether and the aldehyde extracted by a solution of sodium hydrogen sulphite from which i t was regenerated as a readily crystallising oil by the addition of sodium carbonate. The substance was collected and dried and crystallised from light petroleum from which it separated in felted needles melting a t 62O. On acidifying the alkaline solution from which the aldehyde was originally separated a crystalline precipitate was obtained and this was identified as 5-bromoveratric acid. The substance crystal-lised from water in needles melting a t 19l0 and the silver salt was prepared.(Found Ag=29*2. Calc. Ag=29.4 per cent.) The ethereal solution from which the aldehyde had been extracted by repeated washing with sodium hydrogen sulphite was dried and evaporated and a yellow oil remained; this could not be crystallked but was readily converted into a solid nitro-deriv-ative by the action of nitric acid in acetic acid solution in the cold. The substance crystallised from alcohol in pale yellow, slender brittle needles melting a t 1 1 5 O . This substance does not show the properties of a nitrobenzyl alcohol and is unchanged after treatment with acetyl chloride o r with benzoyl chloride in the presence of pyridine. On oxidation with potassium perman-ganate in alkaline solution i t yields the bromonitroveratric acid which is mentioned in the next section.It may be synthesised in the following manner. 5-Bromoveratraldehyde dissolved in a little alcohol was added to a concentrated solution of potassium hydr-oxide and the mixture well shaken from time t o time during three days. The brornohomoveratryl alcohol was extracted with ether, and any unchanged aldehyde removed by shaking the solution with aqueous sodium hydrogen sulphite. The extract was then dried and evaporated and the residue warmed with concentrated aqueous hydrobromic acid. On the addition of water a crystal ORIENTATION OF SUBSTITUTED CATECHOL ETHERS. 923 line substance was obtained which was collected and thoroughly dried and then added to a solution of sodium methoxide in abso-lute methyl alcohol.Sodium bromide separated and after gently warming on the steam-bath during fifteen minutes the addition of water precipitated an oil which was isolated and nitrated and so converted into the substance which is under discusslon This result demonstrates that the nitro-derivative is 6-bromo-5-nitro-4-methozymethylveratrole. Not only has the aldehyde been con-verted by the action of the alkali into the corresponding alcohol, but the latter has been transformed into its methyl ether by the action of the methyl sulphate. 5-BromoueratraZdoxime.-This derivative obtained in the usual manner crystallises from alcohol in needles melting a t 85O. 5-Bromo-6-nitroueratraldehyde; 3-Bronao-4 5-dinitroveratrole, MO’\CHO. MeO/\NO, Me”[ (NO,’ MeOI INO ’ Rr Br \/ \/ 5-Bromoveratraldehyde was dissolved by very gently heating in ten times its weight of nitric acid (D 1*42) and the mixture allowed t o remain overnight when a considerable proportion of the nitro-derivative was found t o have crystallised from the solu-tion.Water was added and the substance collected and crystal-lised from alcohol. There was no evidence of the formation of substances other than the nitro-aldehyde and the colourless needles melted at 1 3 8 O : 0.1310 gave 0.0850 AgBr. Br=27*6. C,H,O,NBr requires Br = 27.6 per cent. The constitution of the substance was proved by oxidation t o the corresponding acid and the transformation of this into a bromodinitroveratrole which could be reduced t o 4 5-diamino-veratrole. The aldehyde was finely powdered and suspended in ili-potassium hydroxide and then oxidised by potassium perman-ganate a t looo during half an hour.The permanganate was added gradually and so that there was always a moderate excess of the reagent. The oxidation of the aldehyde was found not to proceed in a satisfactory manr,er unless the solution was strongly alkaline and this appears to be a general rule for such nitro-aldehydes no doubt because the conversion to alcohol and acid assists the process. After the operation the excess of oxidising agent was decomposed by alcohol and the yellow filtered solution acidified with hydrochloric acid. The colourless precipitate wa collected and consisted of 5-bromo-6-nitroval.atric acid which is sparingly soluble in water and may be crystallised from dilute acetic acid being obtained in colourless bunches of needles melt-ing at 207O.This acid in view of its method of preparation must be remark-ably resistant towards potassium permanganate. It crystallised unchanged from nitric acid (D 1*4) but when boiled with an excess of fuming nitric acid (D 1-52> was transformed into 3-bromo-4 5-dinitroveratrole by elimination of the carboxyl group. The pro-duct was washed with dilute aqueous potassium hydroxide and crystallised from alcohol being obtained in pale yellow needles melting a t 1 2 1 O : 0.1149 gave 0.0712 AgBr. Br=26*4. This substance was also obtained by the action of fuming nitric acid on 6-bromo-5-ni t rover at role. Vigorous reduct ion removed the bromine atom and in order t o ensure the completion of the reac-tion the following method was used.The brornodinitroveratrole (I gram) dissolved in hot alcohol (30 c.c.) was mixed with hydro-chloric acid (5 c.c.) and zinc dust' (10 grams) added in one portion. The stormy reaction over water was added and the mixture boiled during four hours. The solution was filtered mixed with an excess of sodium acetate and with a solution of phenanthra-quinone (1.5 grams) in aqueous sodium hydrogen sulphite and heated t o boiling. The precipitated phenazine derivative was crystallised from acetic acid and then thrice from xylene and obtained in slender yellow needles melting at 260° which were identified with 2 3-dimethoxyphenanthraphenazine (Moureu, Compt. rend. 1896 123 33). C,H70,N,Br requires Br = 26.1 per cent.7 71-Bibromo-5 6 5l 6l-tetramethoxyindigotin, Br '\/ Br This substance was obtained from 5-bromo-6-nitroveratraldehyde by the employment of a method precisely identical with that described above for an isomeride. The indigotin derivative was produced in good yield and was crystallised from nitrobenzene, in which as in all other solvents it is very sparingly soluble and obtained in deep blue needles which have a bronze glance but not a particularly striking one. The substance does not melt o r appear t o decompose a t 360O ORIENTATION OF SUBSTITUTED CATECHOL ETHERS. 925 0.1463 gave 0.1022 AgBr. Br=29'7. The solution in sulphuric acid is intense royal-blue and does not C,,H,,O,N,Br requires Br = 29.6 per cent. change on keeping. 6-Ni t ro u ercl t tyl4 5- t Jhi o t ria 5 o u e ra t ro 1 e (XI).4 5-Dinitroveratrole (9 grams) was dissolved in hot alcohol (300 c.c.) mixed with aqueous ammonia (50 c.c. D O.SS) and the liquid rapidly saturated with hydrogen sulphide. I n a few minutes a crystalline precipitate separated and was collected and crystallised by adding alcohol to its solution in nitrobenzene and then several times from xylene: 0.1174 gave 0.2122 CO and 0.0433 H,O. 0.1260 , 15.4 C.C. N at 19O and 763 mm. W=14*4. 0.1243 , 0.0712 BaSO,. S=7*9. C,,H,,O,N,S requires C = 49.0 ; H = 4.1 ; N = 14.3 ; S = 8.2 per cent. The orange lanceolate prisms melt at 2 1 9 O and this substance is very sparingly soluble in most organic solvents. It dissolves in sulphuric acid to a Bordeaux-red solution and on the addition of water is precipitated unchanged; in this and other respects it fails t o exhibit any basic prcperties.C=49.3; H=4*1. 6-A nzinoueratryl-4 5-t hiotriazoverat role. The nitro-derivative (10 grams) mixed with hydrochloric acid (50 c.c.) and acetic acid (10 c.c.) was heated on the steam-bath with an excess of granulated tin until all the orange compound had entered into reaction and its place was taken by a colourless, crystalline precipitate of the hydrochloride of the new base. Since the separation of this salt appeared to be quantitative it was col-lected dissolved in water and decomposed by the addition of potassium hydroxide. The base was several times recrystallised from alcohol and from toIuene and obtained in characteristic stellar aggregates of colourless leaflets with a satiny appearance, melting a t 114O: 0.1165 gave 0.2272 CO and 0.0558 H,O.0.1317 , 17.4 C.C. N a t 1 6 O and 762 mm. N=15.7. 0.1490 , 0.1006 BaSO,. S=9.2. C,,H,,O,N,S requires C= 53.0 ; H = 5.0 ; N = 15.5 ; S = 8.9 per cent. The pure substance dissolves in sulphuric acid t o a colourless solution but the crude material contains an impurity which develops a rose colour under these conditions and this becomes deep blue and finally violet on the addition O E water. The salts of the base are rather sparingly soluble and the hydrochloride C=53*2; H=5-3 926 JONES AND ROBINSON EXPERIMENTS ON THE crystallises from hot water in slender colourless needles and on the addition of ferric chloride to its dilute aqueous solution a splendid deep blue coloration slowly appears.This reaction is characteristic of many veratrylamine derivatives and is the result of oxidation which in the case of homoveratrylamine was shown (Luff Perkin and Robinson T. 1910 97 1137) t o lead to the production of a p-quinone by elimination of tho amino- and methoxy-groups. There was evidence that the reaction proceeded in a similar direction in the present instance but the quinone could not be isolated in a pure condition. The base is diazotisable and the azo-&naphthol derivative is intense crimson and was obtained in part' in a colloidal condition, so that even a filtered solution appeared to have violet fluorescence, due however to suspended particles. The acetyl derivative of the base could not be obtained in a crystalline condition.It is produced on warming the amine with acetic anhydride and after the addition of water a clear solution is obtained from which the acetylamino-compound is precipitated only by the addition of alkali. It is not diazotisable and gives no colour with ferric chloride so that the acetylation being complete i t is evident that basic function can in some circumstances be exercised by the heterocyclic nucleus contained in these curious substances. 5(or 6)-Nit~o-6(or 5)-amino-1 2 4-trimethoxybentene, NH2 NO2 M ~ o / \ N H , 01' M~O()OM~ MeO/\NO, M~o!,)oM~ The behaviour of dinitroveratrole on reduction with ammonia and hydrogen sulphide induced us to investigate other cases of a similar character and having in our possession a specimen of 5 6-dinitro-1 2 4-trimethoxybenzene (Blanksma Chem.TVeekbZad, 1912 9 440) we applied the reaction t o this sttbstance and obtained as sole product a nitroamine. A mixture of 5 B-dinitro-1 2 4-trimethoxybenzene (7 grams) ethyl alcohol (100 c.c.) and aqueous ammonia (80 c.c. D 0.88) was saturated in the cold with hydrogen sulphide and then boiled under reflux during half an hour. The liquid was diluted with water and allowed to remain in the ice-chest when long yellow needles gradually separated and were collected and crystallised from water and then from a mix-ture of benzene and light petroleum (b. p. 50-60°). The sub-stance crystallises in bright orange-yellow needles or in well-defined orange prisms melting at 118O ORIENTATIOX OF SUBSTITUTED CATECHOL ETHERS.927 0.1146 gave 0.1986 CO and 0.0538 H,O. C,H,,O,N requires C = $7.4 ; H = 5.2 per cent. The melting point of this substance was quite sharp and the appearance of the crystals did not vary so that i t seems that only one of the two possible nitxoamines was actually obtained. The base dissolves in concentrated hydrochloric acid but a pale yellow hydrochloride soon separates in prisms. On the addition of water the salt is decomposed and the orange base precipitated and on the further addition of a solution of sodium nitrite a clear yellow solution of a diazonium salt is produced. The latter gives with excess of sodium acetate and P-naphthol a scarlet azo-compound dissolving in sulphuric acid to an intense blue solution which beconies crimson on the addition of water.C=47*3; H-5.2. 1 2-Methylenedioxyphenanthraphenazine, 4-Bromo-5 6-dinitrocatechol methylene ether (4 grams) and tin (5 grams) were mixed with a solution of stannous chloride (10 grams) in concentrated hydrochloric acid (15 c.c.) and acetic acid (10 c.c.) and shaken in a bottle a t the ordinary temperature until the solid nitro-compound had disappeared The solution was diluted and the tin eliminated as sulphide and after boiling the filtered liquid excess of sodium acetate and then a solution of phenanthraquinone (3 grams) in hot aqueous sodium hydrogen sulphite was added. The mixture was boiled during three minutes, and the yellow precipitate was collected washed with boiling water and dried. It was then dissolved in boiling acetic acid and the solution distilled until crystallisation commenced ; the material 80 obtained had a bronze lustre in mass but under the microscope was seen t o consist of transparent yellow elongated rectangular prisms.For analysis the substance was recrystallised from toluene and obtained as a copper-bronze powder consisting of leaf-shaped crystals. It melts a t 307-309O and is very sparingly soluble in most organic solvent8: 0.1282 gave 0.3648 CO and 0.0448 H20. C2,HI2O2N2 requires C = 77.7 ; H= 3.7 per cent. The substance dissolves in sulphuric acid to a rose-red solution, but is especially characferised by the intense green fluorescence exhibited by its yellow solutions in neutral organic solvents. The C=77.6; H=3*9 928 ORIENTATION OE' SUBSTITUTED CATECHOL ETHERS.isomeric 2 3-methylenedioxyphenanthraphenazine gives very pale yellow solutions which exhibit violet fluorescence. 4-Bromo-1 2-dirnethoxyp.hennnthrapherzcrzi?ze, 4-Bromo-5 6-dinitroveratrole was treated exactly as described for the methylenedioxy-derivative in the last section but the pre-cipitated phenazine was in this case crystallised from xylene. Bright yellow clusters of needles melting a t 206-208O were obtained and t'he same substance was produced by the bromination of 1 2-dimethoxyphenanthraphenazine in acetic acid solution and suspension : 0.1083 gave 0-0493 AgBr. Br=19*4. The solution in sulphuric acid is reddish-purple and in benzene C,,H,,O,N,Br requires Br = 19.1 per cent. or alcohol yellow with weak green fluorescence.1 2 4-T~imethoxyphenaIzthrap~enazine, OMe N /\/\\/CGH4 I I j \/\//\UGH4 OMe N The nitro-aniline (0.5 gram) obtained as described above by the reduction of 5 6-dinitro-1 2 4-trimethoxybenzene was dissolved in hot alcohol (10 c.c.) mixed with concentrated hydrochloric acid (3 c.c.) and zinc dust added until the solution was quite colour-less. After diluting with water the filtered liquid was saturated with sodium acetate and mixed with a solution of phenanthra-quinone (1 gram) in aqueous sodium hydrogen sulphite. The mixture was boiled during five minutes and the precipitated phen-azine derivative was then collected and crystallised from alcohol, from which i t separated in bright yellow felted needles melting a t 186O: 0.0992 gave 0.2729 CO and 0.0449 H,O. The substance is sparingly soluble and Its dilute solutions do The solution in sulphuric acid C=75*0; H=5-0. C,,H,,O,N requires C = 74.6 ; H = 4.9 per cent. not exhibit visible fluorescence. is magenta and becomes brownish-green on dilution with water SCISSION OF SUBSTITUTED CYCLIC CATECROL ETHERS. 929 1 2 3 -Trimethoxyphenalt~irup~~enazine, Dinitropyrogallol trimethyl ether (Will Ber. 1888 21 612) was converted into a phenanthraphenazine derivative by reduction with zinc and hydrochloric acid in alcoholic solution followed by condensation with phenanthraquinone dissolved in sodium hydrogen sulphite solution in the presence of excess of sodium acetate. The substance was crystallised from acetone and obtained in pale yellow needles melting a t 180°: 0.1133 gave 0.3110 CO and 0.0487 H,O. C,3H,,03N requires C = 74.6 ; H= 4.9 per cent. The solution in sulphuric acid is in tense reddish-purple and on the addition of water becomes reddish-brown. Much water precipitates a red substance and the solution becomes colourless. Dilute solutions in benzene o r alcohol are non-fluorescent,. The substance is quite distinct from the 1 2 4-trimethoxyphenanthra-phenazine described above. UNIVERSITY OF SYDNEY. C=74.8; H=4.8. [Received September 4th 1917.