912 MELDOLA AND HOLLELY :

XCIIL-Quinone-A namonium Derivati fves. Pwt 1. The Methylatio.iL Products of Picramic and is0 Picr.ccrr& Acids. By RAPHAEL MELDOLA and WILLIAM FRANCIS HOLLELY.

IN a note published by one of the authors in 1910 (Proc., 26, 232), a trimethylisopicramic acid was described as resulting from the methylation of isopicramic acid by methyl sulphate in the presence of alkali. The analysis of this compound, taken in conr?exion with its non-phenolic character, appeared to indicate that both the hydroxyl ?nd amino-groups had been methylated, and that 2 : 6-di- nitrodimethyl-p-anisidine, a t that time unknown, had been obtained, and the corresponding formula was provisionally assigned. In view of the remarkable properties of the compound, and especially its high melting point and bright colour, its study was continued with the object of getting further evidence concerning its constitution. The compound in question melts above 300°, is non-phenolic, and basic in character; i t separates from the alkaline liquor after com- pletion of the methylation in bright red needles, crystallising from boiling water on cooling, and dissolving in dilute mineral acids to a colourless solution from which the original red compound is precipitated by alkali. The air-dried red compound loses water on drying at; loo3, and changes from bright red to an ochreous colour. According to the constitution at first assigned, the compound might be expected to result from the inethylation of the 2 : 6-dinitro- 11-anisidine (m. p. 3 1 2 O ) , described i i i a former conimunication to the Society (Ueldola aiid Stephens, Trans., 1905, 87, 1304). Some of this compouiid was therefore methylated by methyl sulphate iii presence of alkali in the usual way, but the product was quite different from that formerly obtained by the methylation of isopicramic acid by the same method. Whilst the research was in progress we learnt from a private communication from Dr. F.

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QUINONE-AMMONIUM DERIVATIVES. PART I. 913

Reverdin, of Geneva, khat a compound isomeric with the original substance of high melting point obtained from isopicramic acid had beeu obtained by him by methylating the above dinitroanisidine with methyl sulphate in methyl-alcoholic solution. An interchange of specimms led to the conclusion that the new isomeride obtained from the dinitroanisidine by Reverdin’s method was the true dinitrodimethyl-panisidine. It appeared also that when the dinitroanisidine is methylated by methyl sulphate in presence of alkali some dinitromonomethyl-p-anisidine is also formed, the product consisting of a mixture of the mono- and di-methyl deriv- atives of 2 : 6-dinitro-p-anisjdine. The new dinitrodimethyl-p-anisi- dine has been since described by Reverdin and de Luc ( J . p. Chem., 1911, (ii], 84, 555).

From the foregoing results it follows that isopicramic acid and its methyl ether give totally different products when methylated by methyl sulphate in presence of alkali. The methylation of isopicramic acid was originally studied in our laboratory with the object of preparing compounds containing an asymmetric quinque- valent nitrogen atom combined with a t least one radicle of a s d - ciently acid character to confer acid properties upon the whole molecule of the ammonium derivative. The hydroxyl group is so well protected in this dinitroaminGpheno1 (I) that it was anticipated

OH O H

No2002 NH2

(1.1 W.) that any process of alkylation would, through steric hindrance, result in alkylation in the amino-group only. That the product of extreme methylation is a trimethyl derivative *has been confirmed by numerous analyses of the original compound and its derivatives. It is shown in the present paper that the anticipated concentration of the process of substitution on the amino-group has been verified to an extent quite beyond any preconceived possibility, since all three methyl groups are shown to be attached to the nitrogen atom of the original amino-group. This conclusion having been estab- lished, it appeared probable that picramic acid (11) might give an analogous compound, since the hydroxyl is in this case also partly protected by the 6-nitro-group. This anticipation has also been verified experimentally, although the yield of trimethyl derivative is not so good as with isopicramic acid, for the obvious reitson that in the latter the amino-group is quite unprotected, whilst in picraslic acid it is partly protected by the hydroxyl group. Picramic

VOL. CI. 3 P

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914 MELDOLA AND HOLLELY :

acid on methylation by the method dedcribed gives, in fact, a mixture of mono-, di-, ahd tri-methyl detivatives ; isopicramic acid, on the other hand, gives only the trimethyl derivative in practi- c8uy quantitative field.

Constitution of the Trimeth.yl Derivativca.

The mom- and di-methyl derivatives of picramic and isdpicramic acids ducribed in the experimental part of this paper are of the okdinary type of alkylated amines, and require no special considera- tion. In the trimethyl derivatives there is no methoxy-group present, as shown by the fact that dinitroanisidine yields a W e r e n t compound when methylated. Three possible formula thus remain for cdbsideration. I n the case of picramic acid the formula are:

..

(11.) isopicramic acid

0-- N O,/\ N 0,

(CH&N--- l i

(I?.)

Of these, formuliE I11 and VI are excluded for several reasons. I n the first place, if these compounds were methyl ethers of the type of Hanteach’a isotlitro(aci)-compounds, they might be expected to be unstable and to lose one methyl group with readiness. This is not the case; the compounds are, in fact, extremely stable, and can only be demethylated by heating with concentrated hydriodic acid, aa in the Zeisel process (see experimental part). In the next place, formube I and I1 or I11 and IV mpresent these coltlpounds as derivatives of the hydroxyphenyltrimethylammonium bases lkhich were first prepared by Griess ( B e g . , 1880, 13, 246; also

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QUINONE-AMMONIUM DERIVATIVES. PART I. 915

Auwers and Wehr, *4nnalen, 1904, 334, 308). That this view is correct is proved by the fact that we have prepared our compounds by the direct nitration of Griess’s bases or their salts. It may be taken as proved, therefore, that the extreme methylation of picramic and isopicramic acids gives rise to compounds in which all three methyl groups are attached to one nitrogen atom. These compounda may accordingly be regarded as deriiativm of the hypothetical quinone-ammonium,

Griess adopted the first (betaine) formula for the anhydrides of his trimethylated sminophenols. This author describes also a compound resulting from the methylation of nitroaminophenol by his method, whioh evidently belongs to the same aeries, and ia, in fact, the mononitro-derivative corresponding with our product from picramic acid (Ber., 1880, 13, 647). This compound is also non-phenolic; it crystallises in yellow needles, and melts and decomposes above 200O.

I n the case of the unsubstituted parent compounds, no question of constitution arises beyond the general question of cross-linking (betaine) as against ketonoid structure. The introduction of the nitro-groups in our compounds complicates matters by introducing the possibility of isonitro(ketonoid)-structure, in which case the compounds would be inner salts with meta-cross linking (formulae I1 and V). On the alternative view they are simply nitro-derivatives of the parent trimethyldjuinone-ammonium compounds (formulae I and IV). The decision between these alternative formulze must for the present remain on open question until further evidence has been obtained. It is considered by many chemists with whom this question has been discussed that the ketonoid structure (I and IV) is improbable as assuming that a quinquevalent nitrogen atom can have all its bonds attached to carbon, a state of affairs believed to be without parallel. We may point out, however, that the conditions are quite peculiar in the compounds under considera- tion, inasmuch as the carbon atom which (on the ketonoid structural theory) is doubly linked to the nitrogen atom is part of a highly acidic ring system. It has already been indicated that on this view the compounds are analogous to the oxides of the tertiary amines, the pinonoid ring functioning as the oxygen atom (Meldola and Kuntzen, Trans., 1911, 99, 2045) :

O:NR, O:CpH,(NO,),:N(CH,),. If this analogy holds good, it follows that quinone-ammonium

derivatives in which three dissimilar radicles are attached to the 3 P 2

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916 MELDOLA AND EOLLELP :

quinquevalent nitrogen atom should, in accordance with the discovery of Meisenheimer (Ber., 1908, 4 1, 3966), be resolvable into optically active isomerides. Experiments having this object in view are now in progress in our laboratory. In connexion with the question of the presence of quinquevalent nitrogen doubly linked to carbon, it is of interest to recall the observations of Pope a n d Harvey (Trans., 1901, 79, 85). These authors, in discussing the mechanism of the optical inversion of amino-compounds, .give reasons for believing in the existence of unstable transition compounds of the type (R,Ra:C:NH3 (see also Pope and Read, Trans., 1909, 95, 180). The substitution of the quinonoid ring for R, and R, and of alkyla for hydrogen would result in the comersion of the unstable hypothetical intermediate compounds required by the hypothesis of Pope and Harvey into stable deriv- atives on the assumption that the quinone-ammonium compounds have an analogous constitution.

Mechanism of the Methylation Process.

The first stages in the methylation of the picramic acids are quite normal, and have been proved to be ordinary substitutions leading to the formation of mono- and di-methylamino-compounds. The extreme stage is reached through the formation of an intermediate trimethylammonium compound followed by hydrolysis of the latter :

The ammonium hydroxide stage (111) is retained in the case of isopicramic acid, as will be seen from the experimental part. Yicramic acid, on the other hand, passes a t once to the anhydro- form, namely, the quinone-ammonium compound (IV). The difference in behaviour of the two isomerides is most simply explained by the recognised principle that anhydridisation takes place more readily between groups in the ortho-position, although, as is shown further on, there are good reasons for assigning a different structural formula to the hydrated product from isopicramic acid.

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QUINONE-AMMONIUM DERIVATIVER. PART I. 917

The Relationship between Colour and Chemical Constitution.

The compounds described in the present paper raise extremely important points in connexion with the general question of the relationship between colour and chemical constitution. We do not consider that there is a t present sufficient evidence to warrant any dogmatic statement of conclusions reached since the constitution of our compounds, so far as concerns internal linking, is, as already stated, an open question. A t this stage of the work we propose, theref ore, offering only some general considerations indicating the directions in which this research bears upon the main question. The facts are : (1) the quinone-ammonium compounds are ochreous ; (2) the ammonium hydroxide (hydrate) form of the compound from isopicramic acid is bright red ; the corresponding compound from picramic acid does not exist; (3) the salts formed by the quinone-ammonium compounds with mineral acids are all colourless.

That the colour is due to the presence of the nitro-groups is proved by the fact that the parent (unsubstituted) compounds are colourless, and that the substitution of halogens for both nitro- groups also gives rise to colourless derivatives. The substitution of bromine or iodine for one of the nitro-groups gives a coloured quinone-ammonium compound, but not so highly coloured as when two nitro-groups are present. Adopting provisionally the simpler formulz, and for the sake of simplicity taking one series only, these facts are summarked below:

0 0 0 0 0

The appearance of colour in those compounds containing nitro- groups might, therefore, be interpreted a8 an indication of a difference in structure between these compounds and their unsub- stituted or halogen containing representatives. As the only alternative formula is that in which an isonitro-group with meta- cross linking is present, this argument, aa far as it goes, is in favour of formulae I1 and V discussed in connexion with the constitution of the trimethylated products. This view receives some support from the fact that the trimethyl derivatives from both picramic and isopicramic acids are of much the same colour.

Whichever view be adopted with respect to the constitution of * This is Griess's coinpound referred to above, and, although belonging to the

ortho-series, is included here for the sake of comparison.

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918 MELDOLA AND HOLLELY :

the free quinone-ammonium compounds, there can be but little doubt that their salta are all of the normal type (I). These salts

(1. ) (11.1 are colourless, and their formation takes place in accordance with the general process of reversion to the benzenoid type if the ketonojd atructure be adopted, or to the rupture of cross linking if the betaine constitution is preferred. The corresponding ammonium hydroxide (hydrate) form might therefore be supposed to possess a similar constitution (11). ‘Here, however, there arises a special difficulty due to the remarkable change of colour observed when the free bases are liherated from their salts by the action of alkali. The quinone-ammonium hydroxide from isopicramic acid is, as already stated, bright red ; the corresponding bromonitro- derivative is orange-red. As these bases give colourless salts, it is fair to conclude that the free bases and their salts have different structures. This difference in structure is bgst explained by considering the effect compound :

0

0

of hydrating the quinona-bmmonium

OH N02{)N0,

i/ N(CH,),*OH

HO OH

N O d ) N 0 2 \/

\/ N W 3 h

(111.) H O OH

I f formula, I is taken, the hydrate may have either formula I1 or 111. Formula I1 represente the base as having the same consti- tution as the salt$, a view which is improbable in view of the striking difference in colour. I f formula IV is ascribed to the quinone-ammonium compound, then the addition of water may lead to V or VI, of which V may be rejected as improbable, since a compound of that structure might be expected to be unstable, and t o pass a t once into 11. There remain only I11 and V I as possible formuk. for the red base, and the decision between these ia for the present left an open question. On either view the compound is represented BB related Bo the “quiaoles ” and pseudo-

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QUINONE-AMMONIUM DERIVATIVES. PART I. 919

bases; it i s highly improbable that such a strongly coloured substance can have the simple aamonium hydroxide formula (IT), all such compounds when coloured having a h quinonoid or ketonoid structure in some part of the molecule. We may refer, for instance, to Kehrmann’s oxyimnaphthaphenaeonium hydroxide (Ber., 1896, 99, 2321), of which both tautomeric forms are coloured and in both of which quinonoid structure is present :

A C6H5 OH

A C,B5 OH

Paraquinonoid form : red. Ortboquinonoid form : bluish-green. As against the simpler formula (11) we may add that all attempts

to prove the presence of hydroxyl by alkylation or acylation have led to negative results.” In favour of formula VI, which represents the base y an “ianer salt ” of an i.ronitro(uai)-compound, the vivid colour may be appealed to, as Hantzsch and his colleagues have shbwa that the mi-ethers of nitrophenols are all highly coloured. Quinoles are, on the other hand, generally colourless, although, so far as we have been enabled to ascertain, no compounds of this class containing nitro-groups is the nucleus have as yet been prepared, and it is impossible to predict what influence upon the colour would be exerted by suoh groups. W e hope to extend the research in this direction.

The existence of the red compound from wopiuramic acid and the non-existence of an analogous hydrate from picramic acid are facts quite in harmony with the quinole (carbinol) structure proposed. Assuming the normal structure for the salts of Crimethylated isopicramic acid, the first result of the substitution of hydroxyl for the acid radicle might be considered to be the normal ammonium hydroxide base (11). The latter would then immerise by the transference of hydroxyl from the nitrogen to the para-carbon atom, with the production of I11 or VI. The passage from the unstable ammonium base into the stable carbinol o r pseudo-base would, on this view, be analogous to the well known transformation of phenylacridium hydroxide into the carbinol or pseudo-base (Hantzsch and Kalb, Ber., 1899, 32, 3109). This view of the mechanism of the process is supported by the fact that when a colourlelsa solution of the quinone-ammonium salt is made alkaline in the cold, the colour of the base is but slowly developed, and the red, crystalline compound only separates out completely after some

i t This might also be athibutad to the highly “proteoted” position of the hydroxyl group, but isopicramio acid, in which the hydroxyl group is equally pro- tected, is distinctly phenolic and is readily acetylated with acetic anhydride in presence of a lii tle sulphuric acid.

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920 MELDOLA AND EOLLELY :

time. If the hot solution of the salt is basified, the red colour of the base appears a t once with full intensity.

The objection to the quinole constitution based on the difficulty of a.dmitting the union of two hydroxyl groups with one carbon atom must be given due weight, but in view of the special configura- tion of these compounds as shown in the proposed formulz this difficulty is not really formidable. It is true that in no known compound of quinole structure hitherto obtained is there reason for believing that two hydroxyl groups are attached to the same carbon atom." I n the compounds from isopicramic acid and the corresponding bromonitroaminophenol, however, the para-carbon atom is in the exceptional position of being attached to two carbon atoms carrying strongly acid radicles (nitro-groups), and is therefore analogous to the middle carbon atom of mesoxalic acid f :

HO OH \I

NO,*C-C-C- NO, .. .. This condition is not realised

carbon atoms is attached to the

NO,-~-~;;;-~-N(CH,),. .. .. with 0

HO OH v

HO*OC-C-CO*O$ in picramic acid, as one of the basic trimethylammonium group,

this configuration the quinole structure with two hydroxyl groups attached to the middle carbon ,atom would be unstable, a view which is in accordance with the fact that the quinone-ammonium compound from picramic acid does not form a hydrate.:

General CAmacters of the Quir~orce-ammonizlm Derivatives.

I n ascribing a quinole structure to the hydrates of nitroquinone- ammonium compounds it is recognised that the proposed type differs fundamentally from that of the true quinoles in having the ternary ammonium group in the position occupied by the oxygen atom in the latter compounds. The stability of our compounds is in these

* This statement applies only to the dry solid ; in aqueous solution, such com- pounds may exist. The unstable hydrate of dimethylquinole may possibly have two hydroxyls attached to the same carbon atom (Bamberger and Brady, Ber., 1900, 33, 3650).

t We are indebted t o Dr. J. T. Hewitt for suggesting this analogy. Z There is a close analogy between our quinone-ammonium derivatives and the

sulphonium compounds recently investigated by Zincke and Brune (Bey., 1911, 44, 185). In this case, also, in which quadrivalent sulphur occupies the position of the quinquevalent nitrogen of the quinone-ammonium compounds, the question of para- cross linking or ketonoid structure again arises, preference being given to the latter by the authors named. The parallelism extends likewise t o colour, the thionium- quinone containing a bromine atom being colourless and the corresponding nitro- derivative yellow,

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QUINOSE-AMMONIUM DERIVATIVES. PART I. 921

circumstances certainly remarkable, since the quinoIe-imines which are formed as intermediate comp.ounds in the preparation of quinoles by the method of Bamberger are extremely unstable, and readily exchange their imino-group for oxygen (Ber., 1900, 33, 3600). These considerations may perhaps be urged in favour of formula VI, in which the nitrogen of the ammonium group is singly, and not doubly, bound to the carbon of the quinonoid ring system. Experiments on the products of oxidation of the quinone- ammonium compounds have been undertaken for the purpose of throwing further light on this part of the subject, but the results are as yet inconclusive. Certain other characters which might be expected to be associated with quinole structure also require investi- gation, and have as yet only been studied in a preliminary way; thus the true quinoles have been shown to be capable of being benzoylated by the Schotten-Baumann method (Bamberger and Rising, Ber., 1900, 33, 3640; Bamberger and Brady, ibid. , 3650), whereas our compounds fail to yield benzoyl derivatives. This property is, however, readily explained by the proposed formula, since the benzoylation of one hydroxyl group would be immediately followed by hydrolysis and restoration to the original type:

..__....._.._. ......

The quiuone-ammonium derivatives, also regarded a8 anhydrides of the quinoles and having a true quinonoid oxygen atom, might be expected to react with hydrazines; so far, however, no hydrazones have been obtained, but this part of the research has not yet been exhausted. It is most probable that this reaction is checked by the steric hindrance interposed by the protecting nitro-groups. The extreme readiness with which the quinone-ammonium compound from isopicramic acid hydrates and dehydrates we regard as giving further support to the view that the two hydroxyl groups are attached to the same carbon atom.

Relationship of the Quimne-amnaonium Derivatives to the Imdnazolium Compounds and Iminazolones.

Not the least important aspect of the present research is the relationship indicated by the above heading. The products obtained by the addition of alkyl iodides to the iminazoles, and described in a series of papers formerly communicated to and published by the Society, are, after the substitution of hydroxyl for the halogen atom, closely related to the quinone-ammonium

* This explanation applies also to the non-formation of an acetyl derivative of the quinone-imonium hydrate previously alluded to.

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922 MELDOLA AND HOLLELY :

derivatives. The i n v d g a t i o n of the latter may therefore be expected to throw further light on the constitution of the former. This part of the subject is not yet ripe for full discussion, but in a general way the nature of the relationship will be seen from the following hypothetical schemes :

NO., NO,

--3

(If.)

\ \/ NO, ly

(111.) Taking the simpler formula (I) for the quinone-ammonium

compound (the alternative ortho-quinonoid structure with meta- cross linking making no difference to the argument), the iminazo- lones m8y be regarded as derivatives of the unknown isomeride (11). Supposing that an acylamino-group could by aome means be introduced into position 3, the resulting compound (111), by the elimination of the groups comprised within the dotted line, would give the iminazolone JT (written on the ketonoid type). This is, of course, a purely imaginary process, but it will serve to illustrate the nature of the relationship between the two series of compounds. There is, in fact, as will be seen on referring to the former papers, a distinct parailelism between the two series. Many (but not all) of the hydrates of the iminazolones are red; the iminazolones are generally, but not always, ochreous. The only quation that now arises is, therefore, whether the red (‘ hydrates ” may not also have the carbinol (pseudo-base) structure. This is possible, but a diffi- culty is here introduced owing to the fact that some of the anhydro- forms, for example, thab from aniline (Meldola and Kuntzen, Trans., 1911, 89, 1291), are also red. Without pursuing this part of the subject further at present, we degire, in calling attention to the foregoing relationship, to indicate the direction in which the two lines of research are evidently converging.

EXPERIMENTAL. Hethylatiom of the Picramcc A. cids d e r Variolcs Conditions. Methylation by methyl sulphate was effected in the usual way

by suspending the crystalline solid in water, adding a slight excw

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QUINONE-AMMONIUM DERIVATIVES. PART I. 928

of the sulphate, and agitating briskly with occasional additions of sodium hydroxide solution, and then allowing the slightly alkaline solution to remain at atmospheric temperature for some hours. The insoluble quinone-ammonium compound which separates out is collected, washed with water, and purified if necessary by dis- solving in hydrochloric acid, filtering the solution, and precipitat- ing by alkali. In the case of isopicramic acid the alkaline filtrate on acidification gives only a small quantity of some resinous by-product, the main product being the quinoneammonium compound formerly described. The alkaline filtrate from picramic acid on aciciification gave an ochreous precipitate, which after being collected, washed, and dried, was separable by boiling alcohol into two compounds, one being left as an insoluble residue, and the other remaining in the alcoholic solution, from which it slowly separates in orange scales on dilution with water. The insoluble product proved to be dimethylpicrarnic acid (4 : 6-dinitro-2-dimethyL aminophenol). The latter is a phenolic compound dissolving in aqueous alkali with an orange colour; it is but very sparingly soluble in boiling alcohol, but can be crystallised from hot glacial acetic acid, from which it separates on cooling as a yellow, micro- crystalline powder melting at 218-220° :

0.1097 gave 0.1706 CO, and 0.0406 H,O. 0 1062 ,, '16.9 C.C. N, (moist) a t 18O and 762.4 mm. N=18*45.

C,HSO,N, requires C=42*27; H,=3*99 ; N= 18.50 per cent. The substance deposited from the alcoholic mother liquor on

dilution was not isolated in a state of purity, but we have satisfied ourselves that it consists of a monomethyl derivative, mixed possibly with a little unmethylated picramic acid. The melting point of the product obtained after recrystallisation from alcohol was 144-145O. It was found on analysis to contain 19.31 per cent. of nitrogen, the formula for a monomethyl derivative requiring 19-72 per cent.

i8oPicramic acid when methylated by methyl iodide and alkali in methyl-alcoholic solution or in water gave only resinoue, indefinite products. When heated in a sealed tube with excess of methyl iodide a t looo for six to seven hours, the acid gave as the main product dimethylisopicramic acid, which is described later. A t a higher temperature (115-120° for three hours) the main product of methylation was the quinoneammonium compound.

Methylation by methyl sulphate in the presence of ammonia instead of sodium hydroxide converts iRopicramic acid into a mixture of the quinone-ammonium compound and the dimethyl derivative, the latter predominating.

Picramio acid when methylated by heating with excess of methyl

C=42.41; H=4*12.

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924 MELDOLA AND HOLLELY :

sulphate a t looo for one hour gave a mixture of mono- and di-methyl derivatives ; no quinone ammonium compound is formed under these conditions. isoPicramic acid when acted on with methyl sulphate under various conditions gave the following results :

Methyl sulphate in methyl-alcoholic solution fails to methylate after several hours' heating on the water-bath. When dissolved in excess of impure methyl sulphate containing free methylsulphuric acid, isopicramic acid gives a mixture of mono- and di-methyl derivatives and no quinone-ammonium compound. The result in this cam is the same, whether the solution in methyl sulphate is allowed to remain at the ordinary temperature for a short time or whether heated on the water-bath for some hours. When pure methyl sulphate is used and the solution kept a t looo for ten minutes, the products are the quinone-ammonium compound and the dimethyl derivative.

Dimethylisopicramic acid (2 ; 6-dinitro-4-dimethylaminoplTte~l), obtained by the above processes, is both basic and phenolic in character ; it dissolves in dilute mineral acids, giving colourless salts, and in dilute alkalis with a claret-red colour. The compound obtained by crystallisation from alcohol consists of dark purple needles with a coppery lustre fusing at 182-183O:

0.0962 gave 0,1492 CO, and 0.0338 H,O. C= 42.29 ; H = 3-90. 0.0737 ,, 12 C.C. N, (moist) a t 16O and 743.2 mm. N=18*54.

C8H,0,N3 requires C = 42-27 ; H = 3-99 ; N = 18.5 per cent.

The acetyl derivative, prepared by acetylating the dimethyl derivative with acetic anhydride in presence of sulphuric acid, crystallises from dilute acetic acid in flat, brown needles with serrated edges melting at 156-158O:

0.1260 gave 16.8 C.C. N, (moist) a t 18'5O and 765.7 mm. N=15*47. C,,H,,O6N3 requires N = 15.61 per cent.

The benmyl derivative, prepared by the Schotten-Baumann method, crystallises from alcohol in small, red scales, and from glacial acetic acid in red, fern-like clusters melting at 178-179O :

0.0884 gave 9.S C.C. N, (moist) at 17'5O and 766.2 mm. N=12.93. C,,H,,06N3 requires N = 12.69 per cent.

The monomethylisopicramic acid contained in the alcoholic mother liquor from which the' dimethyl derivative is crystallised has not been isolated in a state of purity, as it is mixed with some unmethylated isopicramic acid. The whole product on solution in hydrochloric acid and treatment with sodium nitrite gave a quinone-diazide crystallising from glacial acetic acid in ochreous

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QUINONE-AMMONIUM DERIVATIVES. PART I. 925

scales or needles exploding sharply a t about 190°. (Found, N = 26.40.

This quinone-diazide is evidently the same compound as that described in a former paper (Trans., 1905, 87, 1204). On combin- ing with 8-naphthol in alkaline solution it gave an azo-compound, which was identified with that described in the paper referred to ( h c . cit., 1205).

All the products of methylation of isopicramic acid obtained by the foregoing methods give the quinoneammonium compound on further methylation with methyl sulphate and alkali. The compounds described in this section are formulated below :

OH OH O*CO*CH, O*CO*C,H,

NO,f)N(CH,), KO,f)NO, N0, f )N02 NO,f).NO,

C,H,O,N, requires N = 26.67 per cent.)

\/ N (.CH3)2

\/ \/ WHJ2 W H , ) ,

v NO2

X. p. 182-183". M. p. 156-158". M. p. 178-179". M. p. 218-220".

The Quinone-a.mmorciuni Compounds.

4 : 6-Dinitro-2-trimethylammonium-l-b ensoquinone.

0 0-1

The ochreous insoluble residue left on by methyl sulphate and alkali can be

methylating picramic acid purified by dissolving in

hydrochloric acid and precipitating by ammonia or by crystallisa- tion from boiling water, from which it separates in ochreous needles having no definite melting point, but decomposing at 275-280° :

0.0933 gave 0.1530 GO, and 0-0402 H,O. c=44*72 ; H = 4.78. 0.0950 ,, 0.1558 CO, ,, 0'0418 q0. C=44.72; H=4*88. 0.0925 ,, 13.85 C.C. N, (moist) a t 18-5O and 766.6 mm.

N=17*41. C,H,,0,N3 requires C =44*78 ; H = 4-60 ; N = 17-43 per cent.

The compound when allowed to dry in the air is anhydrom, and undergoes no loss a t water-oven temperature. Attempts to acetylate and benzoylate the compound led to negative results. Although basic to the extent of dissolving in dilute mineral acids, the salts are easily dissociable, and cannot be isolated for analysis. A pZatinicMode which crystallises in pale, ochreous needles separates on mixing solutions of the chloride and platinic chloride. This salt also begins to dissociate on washing with water or alcohol,

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926 MELDOLA AND HOLLELY :

a3 shown by the analytical results. (Found, P t s 1 9 . 8 and 18.9. (CgH,,0,N3C1)2PtC14 requires Pt = 21-85 per cent.)

The demethylation of the compound has been effected under various conditions. A quantitative determination of the methyl groups eliminated by heating with hydriodic acid indicated that complete demethylation occurred. 0.1045 Gram waa heated in B

current o'f carbon dioxide with 15 C.C. of hydriodic acid (D 1.7) and 5 grams of ammonium iodide €or two and &half hours a t 210O.

C,H,,O,N, - 3Me requires a Ioss = 18.7 per cent. Found, AgI = 0.2965 ; Me = 18.2.

Less complete demethylation was effected by heating the com- pound in a sealed tube with concentrated hydrochloric acid to 130° for two hour9. On opening the tube, methyl chloride was evolved, and the acid solution, on dilution with water and on being made alkaline by sodium hydroxide, gave an orangecoloured solution from which only a trace of unchanged substance was removed by filtration. The alkaline filtrate, on acidification, gave a yellow precipitate, which, after being collected, washed, and crystallised from alcohol, was identified as dimethylpicramic acid (m. p. 218-220O):

0,0824 gave 13.05 C.C. N, (moist) a t 14.5O and 748.5 mm. N = 18.29.

C8Hg0,N, requires N = 18.50 per cent. The alcoholic mother liquor from which the dimethyl derivative

had separated gave, on dilution, a small quantity of the mono- methyl derivative previously referred to, but this product was not further investigated. The main product of demethylation under the conditions specified is dimethylpicramic acid.

Synthesis fro rn o-Eydroxy phen yl trime thylammo riizcm Hydroxide. -0-Aminophenol was methylated in methyl-alcoholic solution by methyl iodide and potassium hydroxide, according to the method of Griess already referred to (Ber., 1880, 13, 246). The crys- talline methiodide, after purification by crystallisation from water, was converted into the nitrate of the ammonium base by decom- position by means of silver nitrate. The solution of the nitrate, after filtration, waa evaporated t o dryness on the water-bath, and the dry crjs$alline residue dissolved in small portions in fuming nitric acid. After some hours the nitric acid solution was poured into water, and made alkaline with ammonia. The ochreous needles which separated proved to be identical with the product of methylatiou of picramic acid ; decomposing point 275-280° :

0-1262 gave 18.9 C.C. N2 (moist) a t 17.5O and 763.5 mm. N117.42. CDH,,0,N3 requires N= 17.43 per cent.

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QUINONE-AMMONIUM DERIVATIVES. PART 1. 927

g(CH&-‘ g(CH3)3- I

The red, crystalline deposit which collects in the alkaline solution on methylating isopicramio acid by methyl sulphate and sodium hydroxide is the “hydrate” of the above quinone- ammonium compound, and most probably possesses the quinole structure previously assigned, The compound crystallises from hot water in long, bright, red needles, decomposing above 300O. An air-dried specimen gave the following results on analysis :

0.1062 gave 0.1630 CO, and 0’0512 H,O. 0.1128 ,, 15.9 C.C. No (moist) at 22-5O and 770.5 mm. N=16*15. CgH130,NS requires C = 41-67 ; H = 5.05 ; N = 16.22 per cent.

The constitution of this “hydrate” has already been discussed. The compound is quite stable at the ordinary atmospheric tem- perature, but loses its water readily in the watet-oven:

C=41*85 ; H= 5.35.

0.7584 lost 0.0524 Ef20 = 6’90. 0’5855 ,, 0’0408 %0=6*96.

C,H,,O,N, requires a loss = 6-95 per cent. The change of colour on drying is most striking, the bright

red needles becoming of a.n ochreous yellow and disintegrating to a microcrystalline powder. The quinone-ammonium compound gave the following results on analysis :

0.09‘75 gave 0.1594 CO, and 0.0412 H20. 0.0970 ,, 14.6 C.C. N, (moist) at 18.5O and 764.5 mm. N=17*45. CgHl1O5N3 requires C=44.78; H=4.60; N=17.43 per cent.

The properties of the compound, as described below, must be understood to refer to both the quinole and quinone-ammonium forms, since the latter is readily convertible into the former by rehydration, and both forms pass into the normal ammonium type on conversion into salts. The ochreous quinonoid compound slowly becomes red in contact with cold water, this conversion into the quinole also taking place immediately when the compound is treated with hot water. It is of interest to place on record the fact that the reverse change-conversion into the quinonoid form- is brought about immediately by a strong aqueous solution of h y d r a h e , which in this cme appears t o act simply &s a dehydrating agent.

The salts of this compound exist only in presence of an excess

Cl=44.58; l3=4*69.

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928 MELDOLA AND HOLLELY:

of the acid; they are readily dissociable by water or by exposure to the air, and no satisfactory analytical results could be obtained. The bromide is formed when the base is dissolved in concentrated hydrobromic acid solution, and crystallises in colourless, prismatic needles on adding alcohol and ether. An air-dried specimen con- tained Br = 23-24, whereas theory requires Br = 24.82 per cent.

The nitrate separates in colourless prisms from a solution of the compound in hot, dilute nitric acid; it dissociates into the red quinole immediately on washing with water. An iodide crystallising in large, ochreous scales, which are brown by transmitted light, is formed by dissolving the base in hydriodic acid (D 1.5) and adding boiling alcohol to the solution; the salt cryd-iallises out on cooling. A specimen washed with alcohol and ether and allowed to dry in the air gave results indicating that a periodide had been formed :

0-140 gave 0.1539 AgI. 1~59.39. 0-1160 ,, 6-55 C.C. Nz (moist) a t 18'5O and 752.4 mm. N=6*44.

C9H1205N31,J2 requires I= 61.13 ; N = 6-74 per cent. The general characters of this salt accord well with the view

that it is a periodide, the low percentage of iodine being due to dissociation. Attempts to purify it by recrystallisation led to further dissociation.

A platinichloride crystallises out in pale, ochreous scales when a solution of platinic chloride is added to a solution of the chloride. These crystals change on exposure to the air into minute, ochreous needles, analyses of which indicated that dissociation had taken place. (Found, Pt=20*18 and 20-09, instead of 21.85 per cent.) D eme thjlation, of the Qwinone-ammonium Cornpowd-The study

of the action of hydriodic acid on this compound led to the discovery that the methyl groups are not so readily eliminated as in the corresponding compound from picramic acid. This result is quite in harmony with the general principle that displaceable groups are more easily removed from the ortho- than from the para-position :

0.1039, when heated in a current of carbon dioxide with 15 C.C. hydriodic acid (D 1.5) and 5 grams of ammonium iodide to 205-210° for two and a-half hours, gave AgI=0.1987. Me = 12.20.

C9H,,0,N, - 2Me requires a loss= 12.46 per cent. From this result it appears that demethylation in this case

extends only to two methyl groups, the product no doubt being the monomethyl derivative of isopicramic acid, previously referred to as a product of direct methylation.

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QUIPTOKE-AMMONIUM DERIVATIVES. PART I. 929

On heating the compound with concentrated hydrochloric acid to 135-140° in a sealed tube for four to five hours, demethylation to the extent of one methyl group takes place, the product consist ing of the dimethylisopicramic acid previously described. This was isolated by diluting the acid solution with water, filtering, and adding ammonia in excess to the acid filtrate. After the removal by filtration of the unchanged quinone-ammonium compound, the dimethylisopicrarnic acid was precipitated by neutralisation with acetic acid, and identified by its melting point (182-183O) and conversion into its acetyl derivative (m. p. 156-158O) :

0.1260 gave 16.8 C.C. N, (moist) a t 18'5O and 765.7 mm. N=15.47. C,oHl10,N3 requires N = 15.61 per cent.

Synthesis from p-Hydroxyphenyltrimethylammon/izLm Salts.-The compound was prepared by the methylation of paminophenol in methyl-alcoholic solution by methyl iodide and potassium hydroxide according to the method of Griess. The iodide, nitrate, and free base all give the dinitroquinone-ammonium compound on nitration with fuming nitric acid under all conditions. Many attempts were made to arrest the nitration so as to obtain a mononitro-derivative, but without success; the compound either fails to nitrate or passes at once to the dinitro-derivative.

Re&c tion of the Uinitropinone-ammonium Compounds.

The formula assigned to these compounds indicates that diamino- hydroxyphenyltrimethylammonium salts might be expected to result from their complete reduction. The compound from isopicramic acid was reduced by adding the substance in small portions to a warm solution of stannous chloride containing tin and hydrochloric acid, and completing the reduction in the usual way. A white double salt appears to be formed on first introducing the substance into the stannous chloride solution, but this dis- solves as the reduction proceeds. After removal of the tin as sulphide and evaporation of the solution, a white, crystalline chloride was obtained, but this was too soluble to be conveniently dealt with. The free base liberated by the action of alkali was also extremely soluble in water. The whole product was then benzoylated by the Schotten-Baumann method, and the resinous product collected and washed free from alkali. A t this stage the product no doubt consists of the tribenzoyl derivative, but as the compound was resinous and uncrystallisable it was partly hydro- lysed by boiling with alcoholic sodium hydroxide until a phenolic compound was obtained, the removal of the 0-benzoyl group being thus indicated. The compound proved to be the expected 2:6-&

VOL. CI. 3 Q

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930 MELDOLA AND HOLLELY:

b enzoy7dia n i i iao-1 -h ydroxy ph eny l-4-t ra rti e t h y la nimoniic m hydroxide. The free base is a resinous substance, and could not be crystallised, but the salts are beautifully crystalline. The chloride (I) crystal-

OH V ~ H ~ - C O - H N / \ N I H - C O ~ H ,

(I.) &I. p. 159".

O H C,H,*CO- HN/\K H*CO*C,H I I

\/ n (C H3)3*O*C,H,(NO,),

(11.) M. p. 206-207".

lises from hot water in large, silvery scales melting at 159O : 0.5941 gave 0.1941 AgC1. (21 = 8-07. 0.1719 ,, 14.47 C.C. N, (moist) a t 1 ' 7 O and 743.6 mm. N=9.55.

C,H,O,K,Cl,H,O requires C1= '7.99 ; N = 9.47 per cent. The picrate (11) was prepared by basifying the chloride with

sodium carbonate, dissolving the base in alcohol, and pdding to the solution an alcoholic solution of picric acid. The salt crystallises on cooling in yellow needles melting when pure a t 206-207O:

0.0938 gave 0.1936 CO, and 0.0377 H,O. 0'1216 ,, 14.25 C.C. N, (moist) a t 16.5O and 760.8 mm.

C,H,,0,0N6 requires C = 56.28 ; H=4.23 ; N = 13-59 per cent. An attempt to prepare the nitrate by dissolving the base in hot

dilute nitric acid led to the formation of an insoluble compound having none of the properties of a salt. After crystallisation from dilute acetic acid i t consisted of dark ochreous needles melting a t 232-233O. The analytical results indicated that the nitric acid in this case acts as an oxidising agent, removing the trimethyl- ammonium group and giving rise t o the formation of 2 : 6-dibenzoyJ- &amino-p-b enzo puinone :

0

I 1

C = 56.29 ; H= 4.46.

N = 13.64.

.. C,H,-CO-H N/\NII.CO*C,H,

\/ 0

0*0710 gave 0.1802 CO, (H,O lost). C = 69-22. 0.0863 ,, 6.2 C.C. N, (moist) a t 16'5O and 760.1 mm. N=8.35.

C,,H,,O,N, requires C = 69.33 ; N= 8.09 per cent. The dinitroquinone-ammonium compound from picramic acid

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QUINOKE-AMMONIUM DEKlVATIVES. PART 1. 931

on reduction by tin and hydrochloric acid gave a product which indicated that in this case the reduction proceeds further than with the isomeride from isopicramic acid. The proximity of the trimethylammonium group to the hydroxyl so weakens the attach- ment of the former that complete elimination takes place with the formation of diaminophenol :

The nz-diaminophenol thus formed was identified by its colour reaction with nitrous acid, by the isolation of the hydrochloride, C,H,0N2,2HCl, and by conversion into benzoyl derivatives. The latter were prepared by evaporating the acid solution to a small volume after removal of the tin as sulphide, and benzoylating with excess of benzoyl chloride in alkaline solution. The insoluble product, consisting of the trib enzoyl derivative,

was crystallised from dilute acetic acid, and obtained as a white, microcrystalline substance melting a t 240-242O :

(NH*CO *C~H,),C~HCJ* 0 ° ~ * C 6 H 5 ,

0.0986 gave 5.5 C.C. Nz (moist) a t 14O and 770.3 mm. N=6.65. C,H,O,N, requires N = 6'42 per cent.

The tribenzoyl derivative on hydrolysis by heating for a short time with alcoholic sodium hydroxide gives the phenolic dibenzoyl derivative, together with it small quantity of a non-phenolic isomeride possessing basic properties. The latter was not obtained in sufficient quantity to examine'in detail, but it most probably consists of the 4-benzoylamino-1-benzoyloxyderivative (I), the other compound, forming the main product, being 2 : 4-dibenaoyZ&amino- phenol (11) :

O*CO*C,H, OH +2 ('\,NH~CO~C,H,

\/ v NH* co' c6H5 NH*CO*C,H,

(1 . ) (1:. 1 The latter crystallises from dilute alcohol in minute, grey scales

0.1506 gave 11 C.C. N, (moist) a t 16'5O and 765.5 mm. N=8*55. C,H,,O,R, requires N = 8-43 per cent.

melting a t 253-254O :

CITY AND GUILDS OF LONDON INSTITUTE, FIN8RURY TECHNICAL COLLEGE.

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