摘要:

876 ROBINSON A THEORY OF THE MECHANISM OF THE LXXV.-A Theory of the Mechanism of the Phyto-chemical Synthesis of certain Alkaloids. By ROBERT ROBINSON. ALTHOUGH in recent years largelly owing t o the investigations of Pictet and his collaborators there has been a due recognition of the importance of the r6le played by formaldehyde in t h e produc-tion of alkaloids in plants and although it is generally admitted (compare Winterstein and Trier " Die1 Alkaloide," pp. 263-317) that the amino-acids and carbohydrates are the most probable starting points f o r the) majority of phytochemical syntheses yet little pirogress has h e n madel in ascertaining the nature of these prwessm or even in the less ambitious task of formulating possible mechanisms based on laboratory analogies.The details of th PHYTOCHEMICAL SYNTHESIS OF CERTAIN ALKALOIDS. 877 schemes which have been suggested with but few exceptions, involve reactions for which little or no parallel exists in synthetical organic chemistry under conditions approximating to those obtain-ing in a plant. Thus Pictet’s view of the mechanism of the s p -thesis of nicotine was founded on observations of pyrogenic reac-tions of pyrrole derivatives and Winterstein and Trier seek to replace this hypothesis by another according to which the base results from the oxidation of a mixture of pyridine and N-methyl-pyrrolidine (Zoc. c i f . p. 298). Similar ideas have been advanced by Windaus and Knoop ( B e i f r . cliein. Pliysio!. Pnth. 1905 6 392) t o explain the formation of xanthine by the oxidation of a mixture of carhzmide and methylglyoxaline and of histidine by an analo-gous process applied to glycinel and methylglyoxaline.There has thus been a tendency to explain the results observed by the assumption that plants have a t their command enormously powesful reagents that are able to cause substances the properties of which have been investigated with considerable care to undergo transformations which cannot be induced in the laboratory. To a certain extent and especially in regard t o oxidation and reduction, this must be true but i t is probable that this aspect has been exaggerated and that an equally important cause of the variety and complexity of syntheses in plants resides in the highly reactive nature of the substances which function as intermediate products.The point of view reached in the present coinmunication is due t o a development of ideas which owed their inception to the hypo-thesis that the synthesis of tropinone recently described (this vol., p. 762) on account of its simplicity is probably the method em-ployed by the plant and confirmation of this theory was sought and found in the structures of hygrine and cuschygrine which stand t o one another in the same relation as styryl methyl ketone (benzyl-ideneacetone) to distyryl ketone (dibenzylideneacetone). I-Iaving found i t desirable to proceed irom ornithine in order to reach the bases of the pyrrolidine group it was obviously interesting to irquire as to whether similar methods applied t o the homologous lysine would lead to naturally occurring piperidine compounds.This proved to be the case and the investigation was then extended to include the more important of the alkaloids the constitutions of which have been determined. In the schemes given in the sequel, linking of carbon to carbon is traced to two processes only namely, the aldol condensation and the very similar condensatioii of carbinol-amines resulting from the combination of a11 aldehyde or ketone and ammonia or an amine and containing the group * ~ ( O H ) * ~ J * with substances coil taiiiing the group *~H*co*. The latter reaction has been investigated chiefly in connexio 878 ROBINSON A THEORY OF THE MECHANISM OF THE with cotarnine and similar pseudo-bases and the production of anhydrocotxmineacetone (I) may be cited as a typical example : $&H,O,-F H*OH C,H,O,-Y H*CH,*CO*CH, CH,*CH,*NMe CH CH,*NMe +CH,*CO*CII -.+ I (1.1 The condensing agent employed by Lieberniaiiii and Kropf (Bey., 1904 37 211) in this case is unnecessary and the reaction proceeds t o completion in aqueous solution and a t the ordina’ry temperature.111 fact these pseudo-bases are substances which enter into a variety of condensations with the greatest facility and a largo number of substances have been prepared in this way and in most cases in good yield. Employing these admissible methods i t is possible in each ir;stance to obtain the alkaloid skeleton and the further modifica-ticns are usually made by means of oxidatioiis or reductions and by elimination of water with the formation of an aromatic nucleus or occasionally of an ethylene derivative.The more important star t-ing points employed are ammonia and formaldehyde ornithine (arginine) and lysine and degradation products of carbohydrates. Of the latter citric acid is suggested as the source of acetone residues which i t supplies in the form of acetonedicarboxylic acid as the result of oxidation. Seekamp has observed the formation of acetme ( A m a l e ? ~ 1893 278 374) by the photochemical decom-position of a 5 per cent. aqueous solution of citric acid containing 1 per cent. of uranium oxide’ and it can scarcely be doubted that the dicarboxylic acid was an intesmediate product. The author does not however wish t o eniphasise unduly this theory of the source of the acetone residues and i t is interesting to note that Lippmann (Bey.1893 26 3057) found that acetonedicarboxylic acid wm obtained during the spontaneous decomposition of calciunl txisawharate. Further. a reactive acetone derivative may be found in diacetylacetone or other ‘polyketen,’ the formation of which iii plants has been discussed by Collie (T. 1893 63 329; 1907 91, 1806) and in that case the acetyl groups would be removed by hydrolysis subsequent to the condensations. However the occur-rence of the carboxyl group in ecgonine suggests t%hat in the synthesis of cocaine i t is a carboxylated acetone derivative which is the forerunner of the alkaloid. Except in the cases of hygrine and tropinone the carboxyl groups have been omitted from the acetone rests for the sake of simplicity in representation.As a starting point for both quinoline and isoquinoline bases i t has been found convenient t o assume the intervention of acetylglycoll-aldehyde (11) or ha-butene-ap-diol-y-one a substance which has not yet been isolated. It may readily be derived from a pentose o PHYTOCHEMICAL SYNTHESIS OF CERTAIN ALKALOIDS. 879 methylpentose by loss of water and oxidation as shown below and i t is perhaps significant that a methylpelztose quinovose occurs in a state of combination as quinovin in cinchona-bark. OH*CH,-CH(OH)*CH(OH)*CH(OH)*CHO 1 CH,*CH(OH>*CH(OH)*CH(OH)*CH(OH)*CIIO - HzO 1 C H *C 0 C H (0 H ) - C H (0 33 ) C H 0 d. jlOxidat ion I \/Oxidatjon The Pyrrolidiiz e Group. It has recently been demonstrated by Hess (Bey.1913 46, 4104*) that the methylation of an amine with the aid of form-aldehyde is accompanied by oxidation amino-alcohols yielding rnethylaminoketonea The methylating and oxidising action of formaldehyde on ornithine might theref ore yield a carbinol-amine of the pyrrolidine series in accordance with the equation NII,*CH,*CH,*CH,*CH(NH,)*CO,H + CH,O = NHMe*CH,*CH,*CHO -+ ~ ~ ~ * C H ( ~ ~ ~ > N M e ] + NH + GO,. [ Naturally the possibility is not excluded that the oxidation of the amineacid .f- is preceded by the formation of a hydroxy-acid, and ammonia and alcohols may in all cases be intermediate between amines and the aldehydes obtained by oxidation. Further oxidation accompanying methylation might attack both ++ I n which a complete list of references to earlier work by Eschweiler and others will be found.t Dakin ( J . Bid. Chern. 1906 1 171) has applied Fenton's method of oxidation by means of hydrogen peroxide and a trace of ferrous sulphate to the ammonium salts of the amino-acids and has obtained aldehydes, ammbnia and carbon dioxide. Hurtley and Wootton (T. 1911 99 288) find that alloxan effects the same change which had already been observed in the particular instances of the conversion of alanine into acetaldehyde and of leucine into isovaleraldehyde by Strecker (Annalen 1862 123, 363). Quite recently Schweitzer (Biochem. Zeitsch. 1916,78,37) has shown that the tyrosinase from potatoes can oxidise glycine with the formation of form-aldehyde carbon dioxide and ammonia. The ieaction takes place in the presence of an alkali preferably calcium hydroxide and appears t o be accelerated by chlorophyll 880 ROBINSON A THEORY OF THE MECHANISM OF THE ends of the molecule with the production of succindialdehyde -E and methylamine as shown below : NH2*CH2*CH2*CH,*CH(NH2)*C02H + 2CH,O = CHO*CH,*CH,*CHO + CH2*CH(oH) bH2.oH)>h TMe ] + 2NH,hle + CO,.After condensation with acetonedicarboxylic acid and elimina-tion of carbon dioxide hygrine (111) cuschygrine (IV) and tropinone (V) are obtained. The synthesis of the latter base (this vol. p. 762) by means of the reaction here assumed t o occur in nature was accomplished in dilute aqueous solution a t the ordinary temperature. Willstatter (Bey. 1900 33 1161) has already given reasons for supposing that the synthesis of atropine and its con-geners and of cocaine is preceded by that of tropinone and i t is now possible t o add that the carboxyl of cocaine f- is the result of partial decomposition of tropinonedicarboxylic acid possibly occasioned by the formation of the methyl ester or of an acid salt.I n the latter case the process resembles thht which Bandrowski employed for the preparation of propiolic acid from acetylenedi-carboxylic acid (Bey. 1880 13 2340). The question of the synthesis of benzoic and tropic acids is not examined here since there is no evidence from accompanying hydroaromatic compounds as to how these may be derived from the carbohydrates. * Succindialdehyde would be more readily obtained from a diaminoadipic acid which does not however appear to have been isolated.t The simplest substance produced on the cocaine model is probably arecoline a comparison of the formula of which with that of cocaine shows that the only divergences which it is necessary to postulate in the synthesis of the former from that of the latter are the employment of two molecules of formaldehyde instead of one of succindialdehyde and loss of water instead of benzoylation. CH*OBz CH,-CH, Cocaine. Rrecoline. Trigonelline. Arecoline also closely resembles a hypothetical intermediate in the synthesis of nicotine. If it is oxidised as was assumed for tha.t more complex tetra,hydropyridine then the bet.aine t,rigonelline would be obtained PHYTOCHEMICAL SYNTHESIS OF CERTAIN ALKALOIDS. 881 NMe 70 H CH,. CO*CH,*CO,H -+ /\ TH2 YH*OH CH,-CH, NMe NMe /\ 7OZH /\ $!H2 QH*CH*CO*CH,*CO,H -+ QH QH CH,*COMe CH,-CH2 CH2--CH2 (VI.) (111.) NMe 70,H FOpH NMe CH,*CO*CH + HO-$X€ QH2 YHz QH-OH CH,-CH CH,-CH, /\ NMe NMe I i Reduction i J.J. C H-CH* CO,K (Ale) Tropine $-Tropine j 4 ' I Ecgonine I Hyoscyamine Tropa-UH2 I I atropine etc. cocaine. CH2 I I I NMeC'O Renzoyl ecgonine Reduction .1 t-\ i Cocaine .i. \&f+-&f, The condensation product (VI) which forms the source of hygrine may also be the progenitor of nicotine (VIII) and the reactions necessary involve condensation with formaldehyde and ammonia t o a piperidone (VII) containing the nicotine skeleton, after which there are alternative ways of expressing the remaining stages. M M 582 ROBINSON A THEORY CO CO,H Nhle /\/ /\ CO,H*CH C'H-VH QH, CH,O CH,O CH,-CH2 NH, OF THE MECHANISM OF THE -t N Me CH-OH (VTI.) I -H*0 CH 4 (VIII.) The Piperidiize Group.Starting from lysine * (IX) and proceeding as illustrated above in the case of the lower homologue ornithine the formation of the bases X and XI would be anticipated. The latter is the alkaloid $-pelletierine isolated by Ciamician and Silber and by Piccinini from the root-bark of the pomegranate tree and since tropinone has not yet been obtained from natural sources the occurrence of its ring homologue is particularly valuable evidence. The base X has been synthesised by Hess Merck and Uibrig (Ber. 1915 48, 1886) and later identified by Hess and Eichel (Ber. 1917 50, 380) with a methylpelletierine occurring in small relative amount in the alkaloids of the pomegranate tree.CH, / \ O NH,*CH,bCH,*CH,*CH,*CH(NH,)*CO,H y H 2 YH2 (IX.1 OH CH*CH,*COAle \/ * Clearly the source appears in piperine. & Me (X.1 CH,-CI-X-CH, b H 2 kMe 30 UH,-UH-CH I I I (XI.) through cadaverine of the piperidine rest whic PHYTOCHEMICAL SYNTHESIS OB CERTAIN ALKALOIDS. 883 The frequent concurrence of closely related alkaloids such as the pelletierines++ or coniine and its associates is probably t o be explained by variations of sane primary product due t o alternate hydration and dehydration o r by oxidation and reduction. I n this connexion a highly significant discovery has been reported by Hess Eichel and Uibrig (Ber. 1917 50 351) who find that the reaction between amino-alcohols and formaldehyde is reversible.The methylaminoketone (X) for example is decomposed in alcoholic soIution by semicarbazide acetate with the formation of ths demethylated amino-alcohol (XII) and f ormaldehydesemi-CH CH2 /\ /\ \/ \/ ' (X) + p 2 QH2 - - + I CH2 p 2 CH CH*CH,CH(OR)*CH CH CH*CK,*CH,*CH, NIT (XII.) NH j (XIIL) CH2 /\ \/ p 2 I C Li c! H* C H2*UH,* C €3, I I NMe (XIV.) J. CIT, /\ \/ 7% ?"a ,,p2 FH2 -3 CH CH*CH:CH*CH CH CH*CH(OH)*CH,*CH, N €I \/ NH WV.1 CH, /\ \/ _ Y H 2 EH /F2 ( p 2 QHz CH C:CH*CH,*CH CH C*CH,*CH,*CH, NH \-/ N €1 (XVI.) * The imino-ketone pelletierine containing one reactive methylene-group (Hess and Eichel Zoc. cit.) has not yet been completely investigated but on the evidence so far recorded and from analogy i t should be the ketone corresponding with conhydrine or more probably the 3-piperidone obtained ky addition of water to coniceine followed by oxidation.In either case i t will fit into the lysine-acetone scheme. M M" 884 ROBINSON A THEORY OF THE MECHANISM OF THE carbazone. This suggests not only that oxidation accompanies N-methylation and 0-methylation but also that reduction is associated with N-demethylation. Coniine (XIII) N-methyl-coniine (XIV) conhydrine (XV) and coniceine (XVI) represent on this view modifications of the amino-alcohol (XII) and therefore of the normal product (X) from lysine formaldehyde and a reactive acetone derivative. I n the above and also in some of the sections which follow the reduction of alkylamines has been assumed and it may be pointed out that there is evidence that these substances are reducible the reaction probably depending 'on the intermediate formation of an unsaturated or cyclic ammonium hydroxide.Condensations between formaldehyde ammonia and a reactive acetone derivative such as acetonedicarboxylic acid can explain in an astonishingly simple manner the formation of alkaloids con-taining the curious quinuclidine ring system. Ammonia three molecules of formaldehyde and the acetone derivative lead to the formation of the piperidone (XVII) two molecules of which enter another molecule of acetone derivative producing XVIII. This, owing to the stability of the ring system produced undergoes internal aldol condensation and complete reduction then results in sparteine (XIX).00 /\ CO,H*CH CH,*CO,H CH,O CH,O -+ NH8 OH,O co /c* co / I I \ I l l I 1 I CH CH CH,*G'O*CH CH CH, CH OH CH, '\/ (XVIII.) I . PHYTOCHEMICAL SYNTHESIS OF CERTAIN ALKALOIDS. 885 \A/ N (XIX. 886 ROBINSON A THEORY OF THE MECHANISM OF THE CH /'\ / i \ CH CH CH*CH(OH)*CH, 5 2 $ z I CH CH CH*CH:CH, I l l CH(OH)*CH CH CH, \/\/ + N Ccl CO*CH C (0 €I ) - C (0 H ) C H , / / I i / ' I l l - - - ? I 1 I CH CH CH l~edilctiolt CH CH (311, +-CH(OH)*CH CE CH +-CH(OH)*CH C'H CH, N (XXII, CH-C( 0 TI)* C H C(OH)*CH.CH, / CH C'H CH /' I l l o r l l / CH CH C'H - H20 +-CH(OH)*CH CH CH +CH(OH).CH CH CH, \ ! ' \/ N PRYTOCHEMICAL SYNTHESIS OF CERTAIN ALKALOIDS.887 the origin of cinchonine and quinine. The quinoline derivative (XXI) enters the molecule in the manner assumed throughout that is by a carbinol-amine condensation and the remainder of the reactions are of the type already formulated in the case of sparteine. An alternative for the later stages is presented in the scheme which is given below. It is possible that reduction of the diketone (XXII) produces first a n internal pinacone (compare Kipping and Perkin T. 1891 59 214) which after further reduction, undergoes a transformation of the ring system accompanied by elimination of water. With regard to the genesis of the quinoline derivatives required for cinchonine and quinine i t is natural to seek an explanation from the constitution of quinic acid (XXIII) which accompanies these alkaloids in the plant and is readily converted into quiaol derivatives.The coincidence that quinine is also in a sense a derivative of p-aminophenol strengthens the conviction that quinic acid is the source of the quinoline half of the molecule. I n any case it' would seem necessary that the acid should become oxidised t o the ketone (XXIV) so as t o provide the six-carbon system and admit the entry of the nitrogen atom. Further a reactive CH(OH)*CHO I CH*OH ClI-OH CO /\ /\ \ \ CH, /' \ / \ i I I I \ / \\ / CH-OH CH CH-OH UH, CII C(OH)*CO,H CH CO -+ CH,O \/ CH-OH NET, \/ CH*OH (XXIII. ) (XXIV. ) CH(OH)*CHO 1 CH t CH, \ / / CH*OH 888 ROBINSON A THEORY OF THE MECHANISM OF THE CH( OH)*CHO I c1 I c I I I I VHZ0 CH (OH) * CHO I /\A I 1 \A/ N inethylene group is so CH (OH).CHO I CH ir HO*CH,*OCH C CH I I I + CHzO -+ CH N I j -CH(OH)*CHO I /\/\ \/\/ Meal I I N produced enabling the occurrence of the condensation which closes the quinoline ring.This process is formulated below and the heterocyclic nucleus is obtained by a reaction similar to that by means of which quinaldine may be syiithesised from o-aminobenzaldehyde and acetone. In the majority of the complex examples discussed it is obvious that the order in which the reactions may be supposed to occur can be considerably varied without fundamentally altering the character of the suggested processes and in the case of quinine there are several plausible variations of this kind the most important of which is perhaps that the quinoline ring may be closed immediately after the appearance of an acetyl group in a modified carbohydrate such as quinovose and the product inust then suffer further degradation by oxidation of the side-chain.The isoQzcinoline Group. I n the discussion of this large and important group it will clear the ground t o construct’ in the first place a table which it is con-sidered represents the genetic relationships of the more important members PHYTOCHEMICAL SYNTHESIS OF CERTAIN ALKALOJDS. 889 Carbohydrate degradation products + ctnimonia 4 .1 4 Hydroaromatic base (HB) + Hydroaromatic aldehyde (HA) Aromatic base (AB) -++ Aromatic aldehyde (AA) (HB+HA-H,O) Morphine Bulbocapnine is o T h e bai n e 1 Codeine Corytuberine etc.+Thebaine (HB + AA - H20) 4 Glaucine dicentrine (AB + AA - H20) + Norcorydaline + Norlaudanosine -+ Laudanine laudanosine, I I papaverine xanthaline 3. 3. hydrastine Corydaline Norcanadine 4 Csnadine berherine protopine cryptopine. (HI3 + C!H,O) + Pyrogallol derivatire + *4A - H,O 4 Narcotine narceine. [?( AB + HA) -+ Hydrastine norcanadine etc. corydaline.] A. The Hydroaromatic base (XXV) and Aldehyde (XXVI).-The clue to the nature of the hydroaromatic substances from which the isoquinoline bases are derived is given by the constitution of morphine and it is regrettable that general agreement on this subject has not yet been reached. However it is only the “Pschorr formula’’ which it has been found possible to dissect in such a manner as to show a relation with the other opium alkaloids and this formula has been adopted especially since the formuls which it is suggested should replace it cannot without hesitation be accepted as superior expressions of the properties of the substance.By working back from morphine a scheme for the synthesis of the isoquinoline alkaloids by means of aldol con-densations has been deduced and the preliminary stages startin 890 ROBINSON A THEORY OF THE MECHANISM OF THE from ammonia formaldehyde,* a reactive acetone derivative and acetylglycollaldehyde are represented below. CH,*CO*CH(OH)*CHO + CO,H*CO*CI-f,.CO.CO,)-E CH,*CO*CH(OH)*CH(0H)*CH2*CO.CH + CH,O + "I, 4 CO /\ HO*qH CH, H 0' 6H CO e C H CH N H, \/ CH2 co 4 - HzO co co /\ \/ Oxidation HO*S)H EH /\ \/ HO*FH YHz HO-CH C(OH)*CH,*CHO f- CH C~CH,,.CH,*NH, CH CH2 (XXVI.) (HA) 4 - IJpO OH I 3.O H HO/\ HO/\ I ~H,GH,*NH \/ I 'CH,*CHO (XXVII.) (AB) \/ (XXVIII.) (AA) * In all cases where formaldehyde is supposed to enter into a carbinol-amine condensation it is clearly equivalent to assume the intervention of glyoxylio acid or even of an aldehyde R'CHO in which tho group R is readily oxidisable to carboxyl after the condensation. (a) *CO*CH + CH,O + NH -+ *CO*CH,*CH,*NH,. (b) *CO*CH + CHOoC0,H -I- NH + *CO*CH,-CH(NH,)*CO,H. (c) *CO*CH,+CHO*CH,*OH (e.9.) +NH + The amino-acids formed in such reactions must be a-amino-acids and the elimination of carbon dioxide will therefore always be explicable.The ,+ ? *CO*CH,*CH (NH,)*CH,*O PHYTOCHEMICAL SYNTHESIS OF CERTAIN ALKALOIDS. 891 B. Formation of the Aromatic Conzpou~zds.-Simple dehydra-tion of XXV and XXVI leads t o 3 4-dihydroxyphenylethyl-amine (XXVII) and 3 4-dihydroxyphenylacetaldehyde (XXVIII) , and attention is directed to the peculiarity of the constitution of the hydroaromatic substances which renders it extremely improb-able that an orientation in the benzene derivatives other than that observed could result from the process. Oxidation of XXV would however produce a pyrogallol derivative and this oxida-tion might be the result of methylenation of the two adjacent hydroxyl groups preventing the removal of oxygen from the ring. The dihydrobenzene so obtained would then be oxidised to XXIX.co - HZO /'\ \/' CH, (XXV.) O * y c gH -+ ' H2<0 C €3 C C H C H N H C H 0 H OH (XXIX.) C. Elaboration of the Af orpiline Sub-yroup.-The hydro-aromatic aldehyde1 (XXVI) condenses with the hydroaromatic base (XXV) producing XXX,. XXXI and XXXII by a carbinol-amine condensation an internal aldol condensation and by elimination of water. A t this stage, in order to obtain mor-phine it is necessary to assume the! only reduction which is encoun-tered in the whole group. The! hydroxyl group marked ( a ) is in a position with respect to the nitrogen atom which renders plausible syntheses of histidine tryptophane and tyrosine probably involve reactions of this type. In the case of hiatidine the complete representation would be the following : NH QHO NH H'Co21CHoN€€3 CO*CH CHO*CO,€€ -+ In general the group 'CO'CH becomes *CO*CH;CH(N~)CO,H and the carbonyl group can then take part in aldol condensations leading to cyclic structures whilst the carboxyl group may be eliminated or the amino-acid be oxidised to an aldehyde.The adoption of such a view in the case of the forerunner of the isoquinoline alkaloids is favoured by the author but the simpler suggestion is retained in the text in order to avoid undue complexity of the formulae ('IXXX) 'H3 'H3 / \/\ ('XXX) 'HH3 'HD / \/\ "H? H0.b H?*OH HN HA H3*OH \ /\/ H 3 03 'H3 'H3 /\ /\ \/ \/ 'HQ H? H?*OH eJ" H 3 H3*OH ('IIXXX) 'H3 'HH3 - / \ / \ 'H? (")HO*? H?*OH H N H3 H3*OH \ / \ / \/\ 1 /OH \/OH ( 'AXX ) 'H3 "3 / \/\ 'HN 'HD HD-OH \/ 'H? HO*? H()*OH HO*H3 HO*H PliYTOCHEMICAL SYNT-HESIS 0 F CERTAIN ALKALOIDS.893 the1 assumption of the formation of a cyclic ammonium hydroxide and after the reduction morphine (XXXIII) is obtained by N-methylation and elimination of two molecules of water. 0-Methylation in addition provides codeine and thebaine is the result af still further methylation accompanied by loss of two atoms of hydrogen. D. The d rottintic I'hennnthrem ICi(b-,qr~trp.-The coinpound XXSII by symmetrical eliiniiiation of three molecules of water yields the phenol derivative (XXXIV) which by N-metliyla-tion and methylation of two phenolic liydroxyl groups be-comes isotliebaine (XXXV) which Klee (,trclr. Ylumn. 1914, 252 21 1) has sliown accompanies thebaine in Yopacer orien tale.HO(\ I f the hydroxomatic ring of XXXII becomes oxidised as may well happen simultaneously with the 11'-methylation of formalde-hyde one of the *CH(OH)- groups becoming *GO* then elimina-tion of water leads t o XXXVI which by methylation and methylenation provides numerous alkaloids of the corydalis-phen-antlirene type such as bulbocapnine (XXXVII) (Gadamer and Kuntze Arch. Pharm. 1911 249 598). I n glaucine (XXXVIII) and dicentrine (Asahina A mlr . Phcirm., 1909 247 201; Gadaiiier ibid. 1911 249 680) the orientation of the catecliol ether groups silggests that these bases are the resul 894 ROBINSON A THEORY OF THE MECHANISM OF THE of condensation of the aromatic aldehyde (XXVIII) with the hydroaromatic base (XXV) and the condensation which closes the phenanthrene ring may then produce a 4 5-substituted catechol derivati 76.Apart from this the reactions necessary will entirely resemble those required f o r bulbocapnine. E. NorlazLdaizosine and tJte Products obtaiued froin it by the A ction of 3'ornznldekyde.-Norlaudanosine (XXXIX) is the result; of condensation of XXVII and XXVIII as illustrated below (com-pare Wintersteia and Trier Zoc. cit. p. 307) : OH OH I 1 (XXVIII.) HO{) \/ CH2 CH2 I \/ I dH HO/\ I 1 (XXVIII.) CH2 dHO HO/) I y 3 2 CH (XXVII. ) (XXXIX.) Norlaudanosine is ?ub,ject to attack by formaldehyde a t six points and the1 nature of the substances produced largely depends on the amount of oxidation which acoompanies the methylations.( a ) Laudanosine, Com~lete methylation of phenolic hydroxyls and of the imino-CI6Hl7O4N 4- 5CHz0 = Cz1H270,N + 50. group unaccompanied by internal oxidation. (6) Papveri?ie, Metliylation of phenolic liydroxyl and oxidation of the tetra-C,,H,,O,N + 4CH,O = C,,H,,04N -t 2 0 + 2H,O. hydroisoquinoline ring. (c) X a n t 11 alin e (pa pi u e ra ldin e ) , Cl6HI70,N + 4CHz0 = C2,HI9O5N + 3HZO. (d) Hydrastiite, CI6Hl7O4N + 5cHzo = Cz,Hz106N + 3HzO. The essential reaction here is a " Lederer-Manasse " syntliesis, introducing ths group *CH,*OH into the benzene ring. The product then becomes siniultaneously metliylated and oxidised as indicated below PHYTOCHEMICAL SYNTHESIS O F CERTAIN ALKALOIDS. 895 ( e ) The Berb e r k e Sub-group.The establiskxnent of a bridge between the nitrogen and the benzene ring produces norcanadine (XL) and the reaction is of course that which Pictet and Gams (Co~npt. rend. 1911 153 386; Ber. 191 1 44 2480) devised for the synthesis of tetrahydrober-berine : From norcanndine the following are obtained by the action of f ormddehyde : ( a ) Canadine, Methylation of two phenolic hydroxyls and methylenation of C,7H,;O,N -t 3C'HZO = CzOH2I0,N -1- 2 0 + H2O. two more 806 ROBINSON A THEORY OF THE MECHANISM OF THE (8) Berbem'ne, C17H1704N + 3cH20 = C2,-,H1905N + 2H20. The sime processes as with canadine using the oxygen for the convesrsion of the tetrahydroisoquinoline derivative into a true alkylisoq iinolini1.m hydroxide. (y) Protopine, Complete methylenation of norcanadine yields XLI and the action of formaldehyde1 on this substance may produce protopine (XLII) (Perkin T.1916 109 875). C,;H,,O4N + 3CH20 = C,,H,,O,N -t 2H20. This is a reaction of a more hypothetical character than any other introduced in this communication but since a ring-scission in this direction of tetrahydroberberine methohydroxide has been estab-lished by Pyman (T. 1913 103 828) and since these results have been paralleled in the isotetrahydroberberine Eeries in connexion with derivatives of cryptopine (Perkin 7oc. cit. p. 841) there appears to be little improbability in the assumption and the details of the process may follow the partial scheme: I I I CH UH UH bH2 C!?H dH2 \/ \/ \/\' CH,*OH I NH 1 :<OH + \/\/' I N ' I * ' /\OH CH2 / CH, / UH, / (6) C'ryptopi?i.e (Perkin loc.cit. p. 831), This would result from norcanadinel by methylation and methyl-CI7Hl7O,N + 4CH20 = C2,HZ7O,N + 20 + HzO PHYTOCHEMICAL SYNTHESIS OE' CERTAIN ALKALOIDS. 897 enation to forin an isotetrahydroberberine which might yield the bzse by the fcrtlier action of formaldehyde as with protopine. F. Narcotine arid iliarceine.-3 4-Dihydroxyphenylacetaldehyde (XXVIII) and the base XXIX are supposed to condense with formatiov- of the methylene ether of hydroxy-fl-methylnorlaudano-sine (XLIII5 which is conveirked into narcotinel (XLIV) in pre-cisely the manner employed above in the case of hydrastine. The ring-scission of narcotine with the formation of iiarceiiie is similar to the production of protopine and cryptopine except that the further methylation of thel nitrogen is not accompanied by internal oxidation : OH ()OH \/ I C*, OH bH 0.CH,*OH /\O*CH,* OH ,/CH2 I *OH 4C!H2O I --+ HO*CH CH - H,O \ i -+ CH (XLIII.) OMe /\-OM9 1 I-CO \f I CH-o (XLIV.) G. Co3daline.-Notwithstanding the observation of Gadamex (L41.cl~. Phartti. 1915 253 274) that corydaline loses its optical ac-tivity when it is oxidised to didehydrocorydaliiie and that therefore the two asymmetric carbon atoms should be contiguous an alteration in the accepted formula of the alkaloid cannot be considered. Especi-ally is th3 position of the methyl group clearly proved by thel argu-ments of Dobbie and Lauder (T. 1902 81 154) relating to the methylpyridinetricarboxylic acid obtained by them from corydic acid, although a slight modification of the constitution of the latter sub-stance would now be made so as t.0 represent it as a true pyridine derivative and as a betaine (compare Perkin Zoc.cit. p. 836) 898 ROBINSON A THE!ORY O F THE MECHANISM OF THE Corydaline accordingly appears as a methylated norlaudanosine with an ethylidene bridge between the nitrogen atom and the aromatic nucleus a structure produced by the interven-tion of acetaldehyde instead of formaldehyde. Attention may be again directed to the possibility that what may be termed the hemipinic orientation may result from aldol condensation with the hydroaromatia progenitors of 1 liese alkaloids whilst the metahemi-pinic orientation is t o be expected if the condensations are subse-quent to the conversion of the hydroaromatic compounds into catecliol derivatives by loss of water.H. The Conditions affectirig t h e ProductioIL of the isoQuinoline Hnses.-The' problem may be put in the form of a question Why do not alkaloids assumed as above to have a common origin always occur together in the plant? Why for example does not morphine occur i n Hydrnstis caizudensis? It is reasonable to expect some answer to this but not in the circumstances a complete one. I n the parti-cular case mentioned the scheme shows that the molecule must suffer reduction before morphine can be obtained. That there are reducing conditions is clear also from the formation of laudanosine. On the other hand the formation of hydrastine and of berberine follows such a course that all the oxygen available from the methyla-tions is used internally and powerful reducing agents would there-fore appear to bs absent during the formation of t'hese bases.This would be sufti'cient to account for the non-production of morphine. Among other circumstancels that may affect the nature of the end-products are the stereochemical relations of the hydroaromatic sub-stances the rapidity with which these lose water with the forma-tion of aromatic compounds the stage a t which N-methylation occurs the concentration of formaldehyde and other reagents the presence o r absence of enzymes and other catalysts all of which are without doubt connected with the needs of the plant itself. If these varying conditions are taken into account the objection that the siniplicity of the schemes proves too much cannot well be sus-tained.Some of the more remarkable' coincidences encountered in the development of thel foregoing suggestions may now be noted in su-mmary and conclusion. In the pyrrolidine group hygriiie, cuschygrine and tropinone are related by their method of forma-tion and by introducing a piperidone sing into hygrine by means of a reaction entirely similar t o that required for sparteine i t is seen that ;ti1 explanation is provided of the &position of the pyrrol-idine complex in the pyridine nucleus of nicotine. In the piper-idine group the methods are homologous with those1 of the pyrrol-idine group and the nature of the reduced pyridine derivative REDUCTION OF ALIPHATIC NITRITES TO AMINES. 899 which have been obtained from plants is quite in harmony with ths origin from lysine. I n particular the a-propyl chain of coniine is explicable orL the assumption that it represents a reduced acetone residue. In the quinuclidine group the bridged rings of sparteine and quinine are produced by similar methods the application of which fixes the position of the connecting methylene group of sparteine and the vinyl group of quinine. Substances accompany-ing quinine anci cinchonine in cinchona-bark have been found to b2 suitable starting points f o r a synthesis of the quinoline-half of the molecules of these alkaloids. I n the isoquinoline group it is noteworthy that one and the same hypothetical hydroaromatic substance derived in part from a carbohydrate degradation product also required for quinine suffices f o r the production of the whole of the bases of the group the constitutions of which have been elucidated. It is hoped that it will prove possible to employ thiv theory as a working hypothesis in several directions. THE UNIVERSITY, LIVERPOOL. [Received July 23rd 19 17.

ISSN:0368-1645    

DOI:10.1039/CT9171100876

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年代:1917

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REDUCTION OF ALIPHATIC NITRITES TO AMINES. 899 LLXXV 1.-Reduction of Aliphatic Nitrites to Amines. By PANCHANAN NEOGI and TARINI CHARAN CHOWDHURI. NEOGI a.nd Chowdhuri have shown (T. 1916 109 701) that aliphatic nitrites are partly converted into the corresponding nitro-compounds by the action of heat. The conversion com-mences at about looo and the best results ar0 obtained a t 125-130°. If however the temperature is further raised, secondary reactions take place and in addition to nitro-com-pounds aldehydes and acids are Iormed. By the reduction of aliphatic nitrites in solution alcohol and hydroxylamine or ammonia are obtained but as the nitrites are partly converted into nitro-compounds on heating it follows that on reducing them a t a higher temperature amines should be pro-duced in addition t o ammonia.Gaudion has shown (Ann. Chim. Phys. 1912 [viiil 25 125) that amines are obtained by the reduction of aliphatic nitrites with heated finely divided nickel or copper. The temperature employed by him however was very high namely above 220° in the case of nickel and above 300° in the case of copper temperatures at which the nitrites decom-pose giving secondary products. He therefore obtained a mix-ture of mono- di- and tri-alkylamines in the reaction. We have, V O L CXI. N 900 NEOQI AND CHOWDHURI : however made experiments at as low a temperature as 100-130°, and have been able to show that the corresponding monoalkyl-amine alone is obtained thus conclusively proving that the resultant amine is the direct product of reduction of the nitro-compound best formed a t 125-130° as previously shown by us.That nitro-compounds are reduced to amines when a mixture of hydrogen and the nitro-compounds is passed over heated nickel has already been shown by Sabatier and Senderens (Cornpit. rend., 1902 135 226). E X P E R I M E N T A L . A slow stream of pure hydrogen was passed through a flask containing the aliphatic nitrite and the mixture of hydrogen and nitrite vapour then passed into a combustion tube about 90 cm. in length filled with reduced nickel and heated in an asbestos box pjrovided with a thermometer. The air was first expelled by the current of hydrogen and then the mixture of the two gases allowed to pass into the tube. To the other end of the tube was attached a dry test-tube immersed in cold water and connected in its turn with two Erlenmeyer flasks containing dilute hydro-chloric acid.Liquid products of reduction such as alcohols and part of the liquid amines collect in the test-tube whilst the vapour of the escaping amines especially in the case of the lower members and ammonia are arrested in the hydrochloric acid flasks. The liquid in the test-tube which gave the pungent fishy odour of the amines was neutralised with hydrochloric acid and the alcohol distilled off. The alcohol was recognised by its odour and identified by determining the boiling point of its acetate. The hydrochloride of the amine and ammonia in the Erlen-meyer flasks and in the test-tube after distilling off the alcohol was evaporated t o dryness.The amine hydrochloride was separated from ammonium chloride by repeated exhaustion with small quantities of absolute alcohol and ether. Besides recog-nising the amines by Hofmann’s carbylamine reaction and other characteristic tests they were identified quantitatively by pre-paring their platinichlorides. Analysis of these showed that monoalkyl- and not di- or tri-alkyl-amines were formed. One point is important in the preparation of the amine platini-chlorides in the presence of ammonia. It is known that even on repeated exhaustion of a mixture of amine hydrochloride and ammonium chloride with alcohol and ether the amine hydro-chloride is not obtained free from ammonium chloride. On the addition of platinic chloride however to a moderately dilut REDUCTION OF ALIPHATIC NITRITES TO AMINES.90 1 solution of the salts the precipitate which is first produced con-tains all the remaining ammonium chloride together with a little amine hydrochloride If now platinic chloride is added t o the filtrate and the solution concentrated i f necessary shining, yellow crystals are formed consisting solely of the amine platini-chloride. The use of reduced nickel in the powder form as employed by Sabatier and Senderens was not satisfactory. The powder forms a layer inside the glass tube and evidently does not present a sufficiently large surface of contact for the action of ths gases. We tilerefore prepared nickelised ash estos by first soaking asbestos fibre in a concentrated solution of nickel nitrate then drying and heating it in the blow-pipe in a large nickel basin in order to convert the nitrate into the oxide.The glass tube was then filled with the asbestos impregnated with nickel oxide placed in an inclined position and heated a t about 300° in a current of hydrogen when the oxide was reduced t o metallic nickel. The nickeiised asbestos with which a tube can be fully packed is strongly recommended whenever reduced nickel is necessary for work with gases as it presents a very large surface for the react-ing gases with the use of a comparatively small quantity of nickel. When once prepared the nickelised asbestos may be used over and over again. The experiments here described were also repeated with reduced iron but the results were much less satisfactory. isoAniylamine from isoAmyl Xitrite.The products from six experiments in each of which 4 C.C. of The temperature employed the nitrite were used were united. was 1 23-130° : Amine hydrochloride = 1 * 6 grams Ammonium chloride = 3.4 ,, Analysis of the platinichloride of the amine gave Pt = 33.61, The acetate of the alcohol was prepared and identified as iso-whereas isoamylamine platinichloride requires Pt = 33-39 per cent. amyl acetate by its boiling point (137-138O). isoButylamine from isoButyl Nitrite. Seven experiments were performed a t 125-130° using 4 to 5 C.C. of nitrite in each case: Amine hydrochloride = 1.9 grams. Ammonium chloride = 3.2 ,, " 90.2 REDUCTION OF ALIPHATIC NITRITES TO AMINES. Analysis of the platinichloride gave Pt = 35.23 ; calc. Pt = 35.07 isoButyl acetate was prepared from the alcohol and identified per cent.by its boiling point (116-117°). N-Propylarnine from n-Pro pyl Nitrite. Six experiments were made a t 130° using the same quantities as in the previous experiments: Amine hydrochloride= 1.3 grams. Ammonium chloride = 2.9 ,, Analysis of the platinichloride gave Pt = 37.10 ; calc. Pt = 36-93 The acetate of the alcohol boiled a t 10Zo showing that the per cent. alcohol was n-propyl alcohol. Etkylamine from Ethyl Nitrite. As ethyl nitrite is gaseous a t the ordinary temperature it was dissolved in paraffin oil and a 25 per cent. solution was used As the nitrite is very volatile even in solutibn much escaped with-out reduction. As a result of six experiments using 5 C.C. of the solution each time ethylamine hydrochloride (0.62 gram) and ammonium chloride (3.2 grams) were obtained. Analysis of the platini-chloride gave Pt = 39-23 ; calc. Pt = 39.00 per cent. Ethyl alcohol was detected by the iodoform morphine and other tests . Methylamine front Methyl Nitrite. Methyl nitrite was prepared according to the directions given in our previous paper (loc. cit.) and dissolved in paraffin oil. Much of the nitrite escaped reduction owing t o its volatility. About 0.10 gram of the amine hydrochloride was obtained as the result of six experiments. Owing to the low yield of the amine salt and to the presence of much ammonium chloride analysis of the small quantity of the platinichloride did not give good results. Methyl alcohol was recognised by the formic acid morphine, and other tests. CHEMICAL LABORATORY, GOVERNMENT COLLEGE, RAJSHAHI BENOAL INDIA. [Received May 4th 1917.

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DOI:10.1039/CT9171100899

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年代:1917

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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.

ISSN:0368-1645    

DOI:10.1039/CT9171100903

出版商:RSC    

年代:1917

数据来源: RSC

摘要:

SCISSION OF SUBSTITUTED CYCLIC CATECI-TOL ETHERS. 929 LXX VIK-The Scission o j Certain Substituted Cyclic Ccl tech01 Ethers. By GERTRUDE MAUD ~EOBINSON and ROBERT ROBINSON. IT was observed (G. M. Robinson this vol. p. 113) that on attempting t o produce an azoxy-derivative from 4-nitrocatechol methylene ether (4-nitromethylenedioxybenzene) (I) by the action of sodium methoxide in methyl-alcoholic solution the sole product was a nitrophenol although the corresponding reaction with nitro-veratrole proceeds smoothly in the normal manner. On further investigation the nitrophenol was readily identified as 5-nitro-guaiacol (11) and the process appeared a t first sight to be one of reduction. However an altlernative view suggested itself namely, that t.he methoxy-group was derived from the methyl alcohol used as solvent and this was proved to be the case since when ethy 930 ROBINSON AND ROBINSON THE SCISSION OF alcohol was used a quantitative yield of 5-nitro-2ethoxyphenol (111) was obtained.(1.) (1I.j (111.) The mechanism of the reaction is therefore to be represented in the following manner : Blanksma (Chem. Weekblad 1909 6 313) has demonstrated the reversible interchange of alkyloxyl groups in nitro- and especially dinitro- phenol ethers and for example 2 4-dinitro-anisole is changed in ethyl-alcoholic solution in the presence of traces of alkali into 2 4-dinitrophenetole; but in the majority of instances mononitrophenol ethers are unchanged under these con-ditions. I n the case of nitrocatechol methylene ether the greater reactivity may be due to the influence of the oxygen atom in the meta-position with respect t o the nitro-group on the distribution of affinity and this is confirmed by the observation that we find i t impossible to realise a similar reaction in the case of nitroethylene-dioxybenzene (IV) in which substance the oxygen atom is one atom further removed from the point of attack.Cardwell and Robinson (T. 1915 107 255) a showed that 5-nitroguaiacol is obtained by the hydrolysis of nitroveratrole with hydrobromic acid and that its acetyl derivative results when acetylguaiacol is nitrated. Similarly the hydrolysis of nitrocatechol diethyl ether with hydrobromic acid is now found t o yield 5-nitro-2-ethoxy-phenol and the benzayl derivative (V) of this substance is obtained by the nitration of 2-benzoyloxyphenetole.NO2 YH,*Of\NO BzO “‘NO FH,*O()NO, CH”O\/ E d \/ I CH,*O\,NO, (IV). (V.) (VI.) In order to examine the scissioii of the ethylenedioxy-ring we submitted 4 5 6-trinitroethylenedioxybenzene (VI) to the action of ammonia. It was quickly changed to a mixture of 3:5-dinitro-2 4-diamino-@-hydroxyethoxybenzene (VII) and 4 5-dinitro-6-aminoethylenedioxybenzene (VIII). The benzoyl derivative (IX) of the former substance exists in two highly characteristic chromo CERTAIN SURST1TUTE:D CYCLIC CATECHOL ETHERS. 931 isometric modifications which are described in the experimental portion on-p. 938. NO2 NH2 NH,/\NH2 7H2*O/\N02 HO*CH,~CH,.O~ \/ /NO CH,*O!,)NO, (VII.) The substance VII is rapidly and quantitatively hydrolysed by hot aqueous alkali hydroxides with the production of two mole-cules of ammonia and the phenol X which was transformed into the well-known dinitrodiaminoanisole (XI) as shown below.NO2 EO, \/ NO2 NO2 llO/\OH HBr HO/\OH M e 2 S O ) --+ HOI /NO G o $ H O ~ H~*CH,=OI ]NO \/ (X.1 MeO/'O.\le N H ~ NH,/\NH, MeC()NO -f MeO\)NO, I n view of the close analogy which exists between the hydroxyl of the carboxyl group and the hydroxyl of opdinitrophenols it is interesting to note that the substance X shows no tendency to form an internal anhydride. It would be fair t o conclude from this that lactone-formation in some way involves the whole carb-oxyl group and not merely the acidic hydroxyl of that group. I n the nitrophenols it is the whole conjugated system extending from the nitro-group to the hydroxyl that corresponds with the carbmyl in the acids and the steric conditions favourable to lactone-formation are accordingly not necessarily present in the dinitro-phenol (X).The constitution of the dinitroamine VIII was proved by eliminating the amino-group when 4 5-dinitroethylenedioxy-benzene was obtained. The nitro-groups in positions 4 and 5 in trinitroveratrole have previously been shown to be displaceable under certain conditions but this is the first example of the dis-placement of the 6-nitro-group in a trinitrocatechol ether. We are inclined to assign the result to the unexplained influence which a fused ring has on the a-position in rendering atoms and groups (XI.) VOT. 0x1. 0 932 EOBINSON AND ROBINSON THE SCISSION 03’ attached a t this point more liable to substitution and displace-ment.Naphthalene for example yields a-nitronaphthalene on nitration and the reactivity of groups in the 1- 4- 5- or 8-posi-tions in substituted anthraquinones may also be cited. E X P E R I M E N T A L. Prepration of 4-Nitrocatechol Methylene Ether. Salway has shown (T. 1908 95 1163) that the nitration of piperonal yields nitrocatechol methylene ether in addition to nitropiperonal and when the former substance is the object’ of preparation the nitroaldehyde may be converted as described in the foregoing communication into 5-nitro-4-aminocatechol methylene ether (compare p. 915) from which the amino-group may be eliminated in the usual manner. 5-Nitro-4-aminocatechol methylene ether (9 grams) was mixed with alcohol (150 c.c.), sulphuric acid (15 c.c.) and powdered sodium nitrite (5 grams), and the solution boiled during five minutes after which a further quantity of sodium nitrite (4 grams) was added and the heating continued for five minutes longer.The crystalline precipitate obtained after the addition of water was collected and dried and weighed 8 grams. After crystallisation from alcohol the substance melted a t 147O and at the same temperature when mixed with a specimen of 4-nitrocat echo methylene ether obtained by the nitra-tion of piperonal. Formcr f i o i ~ of 5-Nitrogunincol b y the Internction of Nitrocrrtechol Methylene Ether and Sodium Methoxide. Nitrocatechol methylene ether (1.1 grams) was heated on the steam-bath with a solution of sodium methoxide (from 3 grams of sodium and 40 grams of methyl alcohol) until the red sodium salt of the nitrophenol crystallised from the solution.This requires from one to three minutes. After cooling the salt was separated, washed with ether dissolved in water and the solution acidified with hydrochloric acid. The yellow precipitate was collected (1.0 gram when dry) and recrystallised from water when it was obtained in needles melting a t 105O and at the same temperature when mixed with 5-nitroguaiacol. 5-Nitro-2-ethozyphenol (111). An almost quantitative yield of this substance was produced when nitrocatechol methylene ether was treated in ethyl-alcoholic solution with sodium ethoxide under precisely the same condition CERTAIN SUBSTITUTED CYCLIC CATECHOL ETHERS.933 as are described above for the corresponding reaction with sodium methoxide. I n this case no salt separated from the solution but the reaction was as rapid as in the former example. The sub-stance is more sparingly soluble in water and alcohols than is 5-nitroguaiacol and separates from methyl alcohol containing a little water in pale yellow well-defined prisms melting a t 113-114': 0.1478 gave 0.2854 CO and 0.0671 B20. C,H90,N requires C=52*5; H=4*9 per cent. The substance dissolves in sodium carbonate solution and the orange-red colour produced can scarcely be distinguished from that of a similar>solution of 5-nitroguaiacol. I n view of the fact that 4-nitroguaiacol dissolves in sodium carbonate t o a yellow solution this behaviour indicates the constitution of the sub-stance and the matter is placed beyond doubt by the preparation of 5-nitro-2-ethoxyphenol by the two followiiig methods which in the corresponding methoxy-series lead to 5-nitroguaiacol.( A ) 2-Ethoxyphenol was benzoylated by an application of the Schotten-Baumann reaction and the dry benzoyl derivative dis-solved in an excess of cold nitric acid (D 1.42). Undue rise of temperature was checked and after ten minutes the clear solu-tion was added t o water and the precipitated oil induced to solidify by the usual methods. The solid was collected and crystallised from methyl alcohol when i t was obtained in felted masses of slender colourless needles melting a t 101-102° : 0.1108 gave 4.7 C.C.N a t 18O and 762 mm. C,,H,,O,N requires N = 4.9 per cent. 5-Nitro-2-ethoxyphenyl beiizoute was dissolved in boiling ethyl alcohol and hydrolysed by the addition of a solution of three times its weight of potassium hydroxide dissolved in water. After heat-ing on the steam-bath during three minutes i t was found that a sample was completely soluble in water. Excess of alcohol was removed the residue dissolved in water just acidified with hydro-chloric acid and then treated with sufficient aqueous sodium carbonate to restore a faint orange colour to the liquid. Under these conditions the benzoic acid remained in solution and the nitrophenol was precipitated. It was collected crystallised from aqueous methyl alcohol and melted a t 112-114O and at the same temperature when mixed with some of the substance prepared from nitrocatechol methylene ether.( B ) 4-Nitrocatechol diethyl ether * (20 grams) was heated on * 4 5-Dinitrocatechol diethyl ether C,,H,,O,N, does not appear to have been previously prepared. It was obtained in quantitative yield by dissolving the mononitro-derivative in nitric acid (D 1.42). In about half an C=52*7; H=5*0. N=5.0. 0 0 934 ROBINSON AND ROBINSON THE SCISSION OF the steam-bath during three hours with a saturated solution (80 grams) of hydrobromic acid in acetic acid. After the addition of water the solution was rendered alkaline by the addition of sodium hydroxide and the unchanged substance removed by filtra-tion (3 grams). The filtrate was acidified and the precipitated mixture of nitrophenols collected (14 grams).After several crystallisations from aqueous methyl alcohol 8 grams of pure 5-nitrcl2-ethoxyphenol melting a t 112-114O were obtained. The melting point was not depressed by admixture with a specimen of the substance obtained by the method ( A ) described above. The alcoholic mother liquors were added to the aqueous solution from which the crude phenol was separated and the whole was extracted with ether. The recovered mixed nitrophenols were converted into benzoyl derivatives by treatment with benzoyl chloride and sodium hydroxide in aqueous solution and the mixture of the benzoates was then fractionally crystallised from methyl alcohol. The most sparingly soluble substance crystallised in slender needles, and was recrystallised from acetic acid.It melted at 156O and was identified as the dibenzoyl derivative of nitrocatechol. The substance was also obtained in the following manner o-Phenylene benzoate (13 grams) was added to cold nitric acid (50 c.c. D 1-42), when the benzoate became an oil which was well mixed with the acid. After remaining overnight the nitration was completed and hour the dinitro-derivative began t o separate from the solution which was gently warmed to ensure the completion of the reaction. Water was added and the solid collected and crystallised from alcohol from which it separated in characteristic citron-yellow micaceous flakes melting at 11 3" and rather sparingly soluble in alcohol. It is quantitatively converted by nitric acid in sulphuric acid solution to the 4 5 6.trinitrocatechol diethyl ether which Blanksma (Rec.trav. chim. 1905 24 40) has obtained lcly the nitration of 4 6-dinitrocatechol diethyl ether. The substance melted a t 122" and was converted by alcoholic ammonia into 3 5-dinitro-2 4-diarizinophenetole, crystallising from nitrobenzene in hematite-like plates melting a t 257" (Nietzki; Annalen 1882,215 153 and Blanksma Zoc. cit. give 245"). 0.4951 distilled with 10 per cent. aqueous potassium hydroxide evolved NH, which neutralised 40.8 C.C. N/lO-HCl whereas this amount of a substance, C,H,,0,N4 yielding 2NH requires 40.9 C.C. 4 5-Dinitrocatechol diethyl ether dissolved in hot aqueous alcoholic hydrochloric acid was reduced by the addition of zinc dust. The colourless solution was mixed with sodium acetate and filtered.The filtrate was then heated with a solution of phenanthraquinone in hot sodium hydrogen sulphite solution and a voluminous pale yellow precipitate of the phenazine derivative was quickly formed. The substance was collected and crystallised from xylene. 2 3-Diethoxyphenanthraphenazine C,,H,,O,N, crystallises in pale flesh-coloured needles which change on keeping in contact with the solvent into rectangular plates melting a t 230'. It dissolves in sulphuric acid to a bright magenta solution yellow on dilution with water and in benzene to a pale yellow solution which exhibits intense violet fluorescence CERTAIN SUBSTITUTED CYCLIC CATECHOL ETHERS. 935 the derivative had solidified. Water was added and the substance collected and crystallised from acetic acid and acetone.The suh-stance melted a t 156O and a t the same temperature when mixed with the product obtained as above: 0.2091 gave 6.4 C.C. N a t 1 7 O and 756 mm. C,,H,,O,N requires N = 3.9 per cent. After the separation of the relatively small quantity of the dibenzoate a substance crystallised in colourless prisms which is undoubtedly the b enzoyl derivative of 4-nitro-2-ethoxyphenol. It could not' be obtained in a pure condition and always melted over a considerable range of temperature. A few crystals were mechanically separated and it was noted that on hydrolysis a nitrophenol was obtained which gave a pure yellow solution in aqueous alkali whereas nitrocatechol gives a blood-red and 5-nitro-2-ethoxyphenol an orange-red solution.From the mother liquors considerable quantities of the benzoyl derivative of 5-nitro. 2-ethoxyphenol melting a t 1 0 1 O were obtained. N=3*6. 4 5 6-Trinitroethylenedioxybenzene (VI). The ethylene ether of nitrocatechol is less readily nitrated than the corresponding dimethyl or diethyl ethers and it was found desirable t o operate under the following conditions which are more convenient than those employed by Ghosh (T. 1915 107 1591) for the same purpoee: 4-Nitroethylenedioxybenzene (10 grams) was dissolved in nitric acid (100 grams D 1-5) and after remaining overnight at the ordinary temperature water was added and the precipitate collected and crystallised from alcohol. The substance was obtained in prismatic needles melting a t 132-133O and was occasionally also obtained in leaflets melting a t the same tempera-ture.The substance is readily reduced to a diamine which gives a red coloration with ferric chloride and condenses with phenanthraquinone to the sparingly soluble 2 3-ethylenedioxyphem~thraphenazine, which crystallises from acetic acid in clusters of slender yellow needles melting a t 239-240°. The colour reaction in sulphuric acid and the fluorescence in benzene are indistinguishable from those exhibited by 2 3-dimethoxyphenanthraphenazine. 4 5-Dinitroethylenedioxybenzene (22 grams) was finely powdered and dissolved as far as possible in sulphuric acid (100 c.c.) and gradually nitrated by the addition with cooling of nitric acid (20 c.c. D 1.5) in sulphuric acid (20 c.c.).The dinitro-compound It separated from acetic acid in plates. C22HI*O2NZ 936 ROBINSON AND ROBINSON THE SCISSION OF passed into solution and the trinitro-derivative crystallised out. The mixture was poured into water and the colourless solid col-lected and crystallised from alcohol. The substance was sparingly soluble and separated in laminae melting a t 155-156O as state'd by Ghosh (Zoc. cit.). Frcm concentrated solutions i t was obtained in prismatic needles : 0 1169 gave 0.1509 CO and 0'0141 H,O. Each stage in the nitration of ethylenedioxybenzene proceeds in C=35*2; H=1*4. C,H,O,N requires C = 35.4 ; H = 1.8 per cent,. a quantitative manner. 3 5-Dini t7-0-2 4-dicr m in 0-p- h y drox y p t hoxy b e m 4 ne (VII) . This substance is obtained by the action of ammonia on trinitro-ethylenedioxybenzene but when the reaction was carried out in ethyl-alcoholic solution it was found that the percentage of carbon obtained on analysis was consistently about 1 per cent.too high, and the amount of ammonia obtained on hydrolysis with aqueous potassium hydroxide was also greater than the theoretical. This indicated that a diamino-derivative of similar constitution and properties but of smaller molecular weight contaminated the pro.-duct and eventually proof was obtained that the impurity was dinitrodiaminophenetole. The production of this substance clearly showed that the trinitroethylenedioxybenzene under the influence of the alcoholic ammonia was converted in part into trinitro-catechol diethyl ether and accordingly the use of alcohol as a solvent was avoided.The following conditions were ultimately adopted Trinitroethylenedioxybenzene (12 grams) was dissolved in pyridine (50 grams) and heated on the steam-bath under reflux with aqueous ammonia (50 c.c. D 0.880). I n a short time the product of the reaction separated in red needles and a further quantity of ammonia solution (50 c.c.) was then added and the heating continued f o r half an hour. After cooling and adding water the orange-red solid was collected and when dry weighed 9.5 grams. This material is a mixture containing about 75 per cent. of dinitrodiaminohydroxyethoxybenzene and about 25 per cent. of a dinitroaminoethylendioxybenzene. The two sub-stances may be approximately separated by crystallisation from xylene in which the former is the more sparingly soluble.The further purification of the second crop of crystals is described below but the intense red crystals which separate first can be obtained in a pure condition by two recrystallisations from nitro-benzene. It is perhaps better to extract the crude product with hot xylene insufficient to dissolve the whole and then to crystal CERTAIN SUBSTITUTED CYCLIC CATECIIOL ETHERS. 937 lise the residue from nitrobenzene. red needles melting a t 240O: The substance occurs in deep 0-1543 gave 0.2127 CO and 0.0583 H,O. 0.0978 , 18.2 C.C. N a t 2 4 O and 750 mm. N=21*1. C,H,,O,N requires C == 37.2 ; H = 3.9 ; N = 21.7 per cent. 0.3977 distilled with 50 C.C. of 10 per cent. aqueous potassium hydroxide evolved NH, which neutralised 31 0 C.C.NIlO-HCl, whereas this amount of a substance CPH1006N4 yielding 2NH3, requires 30.8 C.C. This substance resembles in its behaviour the similarly consti-tuted dinitrodiaminophenetole. It is quite devoid of basic character and is very sparingly soluble in organic solvents. When its solution in sulphuric acid is treated with sodium nitrite a reaction of unexplained character occurs and on the addition of water there is produced a transient intense purple coloration. This quickly disappears and the yellow solution contains traces of some diazo-salt as indicated by coupling with “R-salt,” but the major part of the substance has undergone decomposition. C=37*6; H=4*2. 3 5-Diiiitro-2 4diamino-P-b enzoylozyethoxyb en z e u e (IX).It was noticed that the amino-groups of dinitrodiaminoanisole and the corresponding phenetole derivative cannot be benzoylated by the action of pyridine and benzoyl chloride on these substances. Recourse was therefore had to this reaction in order to prove the presence of a hydroxyl group in the substance described in the last section. The dinitrodiaminohydroxyethoxybenzene (4 grams) was dissolved in pyridine (30 c.c.) and benzoyl chloride (15 c.c.). A certain amount of heat was developed and when the reaction had subsided ether was added and the red precipitate collected and washed with water. I t was dried in the air and then crystal-lised from ethyl acetate in which i t is sparingly soluble: 0.1526 gave 0.3800 CO and 0.0560 H,O. C1,H,,0,N4 requires C = 49.7 ; H = 3.9 per cent.0.3827 distilled with aqueous potassium hydroxide evolved NH,, which neutralised 21.5 C.C. N/lO-HCl whereas this amount of a substmce Cl5HI4O7N4 yielding ZNH, requires 21 *2 C.C. On acidifying the alkaline solution from this experiment, benzoic acid and 3 5-dinitro-2 4-dihydroxy-P-hydroxyethoxy-benzene (X) were obtained as a crystalline precipitate. The latter substance was identified after removal of the benzoic acid by repeated evaporations of the solution in water. This benzoyl derivative is dimorphous and occurs in two distinct chromoisomeric modifications. Both forms melt at 180-181O C=50*0; H=4*1 938 ROBINSON AND ROBINSON THE SCISSION OF alone or mixed. The crimson form crystallises readily from most solvents and may be easily obtained by crystallisation from xyleiie or by the addition of ether alcohol or light petroleum to a solu-tion of the substance in pyridine.It occurs in crimson plates with parallel edges. The orange-yellow modification is character-ised by its sparing &solubility in ethyl acetate and is the first to crystallise from this solvent. It is obtained by heating the red form or a mixture of the two to near the melting point and then extracting the material with ethyl acetate. It crystallises from this solvent in needles. The change from red to yellow on heating also occurs slowly a t temperatures above loo@ but nothing in the nature of a transition point could be determined. Recrystallisa-tion of either form from nitrobenzene resulted in crimson leaflets containing solvent of crystallisat.ion.3 5-Dinitro-2 4-dih ydroxy-P-h ydroxy e t hox y b en z ene (X) . This substance was readily obtained by boiling dinitrodiamino-P-hydroxyethoxybenzene with a 10 per cent. solution of potassium hydroxide until all the ammonia was evolved. The reaction was complete in a few minutes and the orange solution was acidified with hydrochloric acid. Bronze-yellow needles separated on cool-ing and the substance was purified by recrystallisation from dilute hydrochloric acid. It is readily soluble in water or alcohol less readily so in dilute hydrochloric acid and it has powerful dyeing properties. The substance forms well-defined brit,tle needles which darken at 160° and melt and decompose at 170O: 0.1379 gave 0.1884 CO and 0.0395 H,O.This compound shows no tdndency to change by loss of water to a lactone-like ethylenedioxy-derivative. Its constitution was proved in the following manner The glycol residue was removed by boil-ing several hours with an excess of concentrated hydrobromic acid, and the resulting phenol converted into its trimethyl ether by means of methyl sulphate and potassium carbonate in boiling nitro-benzene solution. This substance was then heated a t looo in a sealed tube with concentrated aqueous ammonia and the resulting red precipitate crystallised from nitrobenzene. The red plates were identified as consisting of 3 5-dinitro-2 4-diaminoanisole and melted a t 255O and a t the same temperature when mixed with a specimen of the substance obtained from trinitroveratrole.C=37.3; H=3*2. C,H,O,N requires c = 36.9 ; H = 3.1 per cent CERTAIN SUBSTITUTED CYCLIC CATECHOL ETHERS. 939 4 Ei-Dini tro-6amino e t h y len edio xy b enz en e (VIII). This by-product of the preparation of dinitrodiaminohydroxy-ethoxybenzene from trinitroethylenedioxybenzene is separated in an impure form by extracting the crude product with xylene as already described. It may be freed from its congener by taking advantage of the ready attack of the latter by warm aqueous potassium hydroxide. The crude crystals obtained from xylane were carefully warmed with a 5 per cent. solution of potassium hydroxide until the precipitate had a pure yellow colour. The substance was then collected washed with water and several times crystallised from ethyl acetate from which i t separated in orange-yellow rhombic prisms melting a t 202O: 0.1133 gave 0.1676 CO and 0.0340 H,O.The substance is sparingly soluble in moat solvents and has weak basic character. On boiling with aqueous potassium hydroxide it is slowly attacked yielding a cherry-red solution. The base is diazotisable in dilute hydrochloric acid suspension and the diazonium salt couples with P-naph tho1 to a crimson azo-compound' When trinitroethylenedioxybenzene is reduced in alcoholic hydro-chloric acid with zinc dust a colourless solution is obtained which gives an intense green coloration with ferric chloride. The sub-stance now under consideration shows the same behaviour. On boiling with alcoholic sulphuric acid and powdered sodium nitrite, the amino-group was easily removed and after the addition of water pearly leaflets separated and were collected.The substance was recrystallised from alcohol and melted a t 132-133O alone or mixed with a specimen of 4 5-dinitroethylenedioxybenzene. Since the conEtitution of the latter substance is known by inference only, the material obtained from the above experiment was hydrolysed by heating with concentrated aqueous hydrobromic acid and the dinitrocatechol so obtained methylated in the usual manner and the product identified with 4 5-dinitroveratrole. A cetyl Deriva tiwe.-The dinitroamine could Be recrystallised from acetic anhydride but on the addition of a trace of sulphuric acid the aminegroup was acetylated and the derivative was col-lected after decomposition of the excess of acetic anhydride by means of dilute hydrochloric acid. The substance was recrystal-lised from alcohol in which i t is sparingly soluble and obtained in hexagonal prisms melting at 257O. The substance appears colourless when first prepared but the compact crystals have a pde yellow colour. C=40.2; H=3.3. C,H,O,N requires C= 39.8 ; H = 2.9 per cent. 0 o 940 HINDMARSH KNIGHT AND ROBINSON : The similarly constit*uted 4 5-dinitro-3-acetylaminoveratrole has recently been prepared by Gibson Simonsen and Rau (this vol., p. 78) who find that it dissolves in aqueous potassium hydroxide t o a yellow solution which on acidification gives a precipitate of the unchanged substance. This ethylene ether shows the same characteristic behaviour. UNIVERSITY OF LIVERPOOL. [Received September 4th 1917.

ISSN:0368-1645    

DOI:10.1039/CT9171100929

出版商:RSC    

年代:1917

数据来源: RSC

摘要:

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

ISSN:0368-1645    

DOI:10.1039/CT9171100940

出版商:RSC    

年代:1917

数据来源: RSC

摘要:

946 ORR ROBINSON AND WILLIAMS : LXXX.-The Action of Halogens on Piperonal. By ANNIE MARY BLEAKLY ORR ROBERT ROBINSON and MARGARET MARY WILLIAM s . THE displaement of groups by nitroxyl accompanying the nitra-tion of phenol ethers has frequently been observed but it does not appear to have been recorded that a similar reaction occurs in the chlorination o r bromination of certain of these substances. I n the preparation of bromopiperonal in acetic acid solution the yield of product is not satisfactory and this caused us to suspect that a certain proportion of the formyl group is displaced by the halogen which we found on investigation to be the case. I n a neutral solvent such as carbon disulphide or carbon tetrachloride, the yields of bromopiperonal and of 6-chloropiperonal (I) are excellent and by-products are reduced to a minimum but in acetic acid solution the bromination of piperonal produces a certain amount of 4 5-dibromocatechol methylene ether (this vol., p.913) and the chlorination of the aldehyde yields 4 5-dichloro-catechol methylene ether (11) in addition to chloropiperonal and substances of undetermined nature which are decomposed by aqueous sodium carbonate and probably owe their formation to attack of the methylene ether group by the halogen. Dichloro-catechol methylene ether was also obtained by the action of chlorine on a sodium carbonate solution of piperonylic acid or of 6-chloropiperonylic acid (111) obtained by the oxidation of chloropiperonal. 4-Chloro-5-bromocatechol methylene ether (IV THE ACTION O F HALOGENS ON PIPERONAL.947 was obtained by the action of bromilze on an aqueous sodium carbonate solution of chloropiperonylic acid but not except in traces from chlorine and bromopiperonylic acid under similar conditions. The behaviour of chloropiperonal on nitration resembles that of bromopiperonal and 4-chloro-5-nitrocatechol methylene ether (V) and 4-chloro-5 6-dinitrocatechol methylene ether (VI) were successively obtained. The latter on reduction furnishes a chlorodiamine which was isolated as a phenanthra-phenazine derivative. (IV) Ex P E R I M E N T A L. Brornination of Piperonal in Acetic Acid Solution. Piperonal (100 grams) dissolved in acetic acid (200 c.c.) was gradually treated with bromine (40 c.c.) dissolved in acetic acid (100 c.c.) any rise of temperature being checked by cooling.After remaining overnight the crystals were separated by filtra-tion and found to be pure 6-bromopiperonal (37.8 grams). The filtrate was mixed with water and the solid collected and heated with an aqueous solution of sodium hydrogen sulphite until no further alda,hyde passed into solution. The substance was then dissolved in ether and the ethereal solution extracted with repeated quantities of aqueous sodium hydrogen sulphite. The bromopiperonal was recovered from the hydrogen sulphite extract by the additicn of sodium carbonate and after crystallisation from methyl alcohol weighed 62 grams. The ethereal solution was washed with sodium carbonate and with water dried and evaporated and the crystalline residue weighed 14.8 grams.It was crystallised from alcohol and identified as 4 5-dibromocatechol methylene ether melting a t 86O. The substance from this source persistently crystallised in needles whereas it had formerly been obtained in leaflets but the melting point of a mixture was 8 6 O . The formation of the dibromo-derivative must be due in the first place to that of the monobromecompound in its turn obtained by a direct displacement of the formyl radicle by bromine. Thi 948 ORR ROBINSON AND WILLIAMS : follows from the observation that bromopiperonal is stable to bromine in acetic acid solution. A specimen was found to be unchanged after the attempted reaction had been prolonged during a week. 6-Chloropiperonal (I). A stream of chlorine was passed into a solution of piperonal (25 grams) in acetic acid (50 c.c.) until the product of the reac-tion commenced to crystallise.This required about four hours. Water was added and the solid collected and dissolved in ether. The ethereal solution was washed with aqueous sodium carbonate and then with sodium hydrogen sulphite solution until a test por-tion gave no milkiness on the addition of sodium carbonate. The ethereal solution was dried and evaporated and the residue (3.4 grams) was identified as 4 5-dichlorocatechol methylene ether. The hydrogen sulphite solutions were treated with excess of sodium carbonate and the precipitated crystalline substance was collected and crystallised from aqueous alcohol when 17.1 grams were obtained. The substance was further purified by crystallisation from methyl alcohol from which it separated in long colourless needles melting at 1 1 5 O : 0.1294 gave 0.1019 AgC1.C1-15.3. 0.2010 in 16.06 C,H gave At=0*347. 6-Chloro-3 4-methyle?zedioxystyryl methyl ketone (6-chEoro-piperonylideneacetone) C,,H,03C1 is obtained by the addition of dilute aqueous potassium hydroxide to a solution of the aldehyde in three times its weight of acetone. After an hour water was added and the nearly colourless precipitate collected and crystal-lised from alcohol. The pale yellow needles melted sharply a t 1 5 8 O and dissolved in sulphuric acid to a reddish-yellow solution, and the substance was recovered unchanged on the addition of water. I n chloroform solution bromine was rapidly absorbed, but the dibromide was oily.Bi-6-chloromethylenedioxystyryl ketone C,9H,20,C1, is obtained by the condensation of the aldehyde with the above described sub-stance or by heating the chloropiperonal in alcoholic solution with acetone and concentrated potassium hydroxide. It is very sparingly soluble and its formation is a matter of seconds. The substance was washed with hot alcohol and crystallised from acetic acid. The felted citron-yellow needles melted and decomposed a t 265O and dissolved in sulphuric acid to an intense blue solution which became purple and then yellm on the addition of water. 6-ChZoro~*peronyZic acid C,H,O,Cl was produced on oxidising M.W.=180. C,H,03C1 requires C1= 19.0 per cent. M.W. = 184 THE ACTION OF HALOGENS ON PIPERONAL 949 the aldehyde in benzene solution by stirring with a 2 per cent.solu-tion of potassium permanganate. The reaction proceeds slowly and when the benzene gave no residue on evaporation the excess of permanganate was destroyed and the acid obtained by acidification of the filtered aqueous solution. It was precipitated as a caseous solid which wm collected and crystallised from acetic acid. The colourless needles melted a t 202O and the substance is very sparingly soluble in water. It gives a pale yellow solution in sulphuric acid which becomes olive-green on gently heating, whereas piperonylic acid under these conditions gives an intense red solution which may be due to a condensation in the ortho-position. 4 5-Dichlorocntechol Methylene Ether (11). This substance may be obtained as already mentioned by the chlorination of piperonal and in this case i t seems that it may be obtained by the further action of chlorine on chloropiperonal, although the reaction is not smooth.It is also obtained by pass-ing chlorine into a solution of piperonylic acid which is always kept alkaline by the addition of aqueous sodium carbonate. Finally the same substance was prepared by chlorinating catechol methylene ether in acetic acid solution. It crystallises from alcohol in slender colourless needles melting at 8 2 O : 0.1218 gave 0.1866 AgC1. c1=37*5. C,H,O,Cl requires C1= 37.2 per cent. The substance is sparingly soluble in sulphuric acid and the solution is colourless but becomes reddish-yellow on the addition of a trace of nitric acid.The reaction is therefore not so charac-teristic as that of the corresponding dibromo-derivative which gives a rhodamine-red solution under these conditions. The con-stitution of the derivative follows from its production from chloro-piperonylic acid which must have the orientation of chloro-piperonal and therefore of chloronitrocatechol methylene ether, which as shown below must be a 4 5-derivative. 4-Chloro-5- bromocat echo1 M e t hyleii e Ether (IV). This substance could not be obtained by t,he chlorination of bromopiperonal in acetic acid solution and only in traces as the result of application of a large excess of reagent by the action of chlorine on an alkaline solution of bromopiperonylic acid. It was obtained in small amount by the bromination of chlore piperonal and comparatively readily by the action of bromine on an alkaline solution of chloropiperonylic acid.It was found tha 950 ORR ROBINSON AND WILLIAMS : the best conditions were to add the bromine water and aqueous sodium carbonate alternately to a dilute solution of the sodium salt of the acid and the completion of the reaction was judged by the amount of the precipitate formed. This was collected and crystallised from methyl alcohol from which i t separated in flat, satiny needles melting a t 78O. 0.1305 gave 0.1829 AgCl plus AgBr whereas this amount of a substance C,H,O,ClBr requires 0-1838 of the mixed saIts. The reaction of this substance in sulphuric acid on the addition of a trace of nitric acid was intermediate between that exhibited by the dichloro- and dibromo-derivatives.The reddish-brown solution appeared carmine in thin layers. A mixture of about ten parts of the dichlorocatechol methylene ether with one part of the dibromo-compound gave a solution almost identical in appearance with that from the chlorobromo-derivative. Application o f the Canizizzaro Reaction t o Piperonal. The formation of piperonylic acid and of homopiperonyl alcohol by the action of sodium hydroxide on piperonal does not appear to have been described and as we required piperonylic acid and the alcohol was being employed in another investigation we made some experiments on the conditions of the reaction and adopted the following procedure. A solution of sodium hydroxide (200 grams) in water (200 c.c.) was cooled to 40° and added to piperonal (100 grams) contained in a bottle capable of withstanding changes of temperature and the mixture vigorously shaken.Alcohol (50 c.c.) was then added and caused an almost immediate reac-tion and rapid rise of temperature. The bottle was vigorously shaken and the pressure released from time t o time. Soon the temperature fell and the mixture was then allowed to remain overnight. It was then mixed with sufficient water to dissolve the sodium piperonylate and extracted with benzene. The aqueous solution gave 53 grams of piperonylic acid on acidification, and from the benzene 1.8 grams of piperonal were recovered by washing with sodium hydrogen sulphite solution and after drying the extract and removing the solvent 32.5 grams of homopiperonyl alcohol remained in a pure condition.It readily crystallised and could be employed in most experiments in this condition. The substance may be recrystallised from light petroleum and occurs in slender colourless needles melting a t 58O. Fittig and Remsen (Annulen 1871 159 138) give the melting point as 51° but their product was purified by distillation THE ACTION OF HALOGENS O N PIPERONAL. 951 4-Chlorod-nitro ca t echoi! Me thylen.e Ether (V). 6-Chloropiperonal was dissolved in nitric acid (D 1*4) and after half an hour the mixture was added to water and the solid col-lected and crystallised from alcohol in which the substance is rather readily soluble. The nearly colourless needles melted a t 70° and became yebw by the action of light: 0.1231 gave 0.0867 AgC1.C1=17.2. C,H,O,NCl requires C1= 17.4 per cent.. This substance was also obtained from 5-nitro-4-aminocatechol methylene ether by diazotisation of the latter in hydrochloric acid and tr'eatment with copper powder. This connects the sub-stances described in the present cominunication with the series of 4 5-disubstituted catechol derivatives. On reduction the sub-stance yields a crystalline amino-derivative which can be diazo-tised and contains chlorine. 4-C'hl oro-5 6-ditzit.rocatech 01 Methyl e m Ether (VI) . The foregoing substance was dissdved in nitric acid (D 1.52), and a rather vigorous reaction ensued which had t o be moderated by cooling. On the addition of water a precipitate was obtained which was collected and crystallised from alcohol.The sparingly soluble yellow needles melted a t 138-141O : 0.1162 gave 0-0670 AgC1. C1=14-1. This substance becomes orange-yellow on exposure to light. C,H,0,N2Cl requires C1= 14.2 per cent'. 4-Chlor0-l 2-methylenedioxyphenant hrapheiurzin e, The dinitro-derivative just described was reduced in alcoholic aqueous hydrochloric acid solution by the addition of zinc dust, and the filtered solution mixed with excess of sodium acetate was heat'ed during two or three minutes with a solution of phenan-thraquir,one in aqueous sodium hydrogen sulphite. The brownish-yellow precipitate was collected and dried and crystal-lised from xylene. Glistening ochre-orange needles separated which melted and decomposed at 298-300° 952 BROWN AND ROBINSON VERATRICSULPHINIDE. 0.1079 gave 0.0422 AgC1. C1=9*6. C,,H,,O,N,Cl requires C1= 9.8 per cent. The substance dissolves in sulphuric acid to a purple solution, and in neutral solvents to yellow solutions which exhibit intense green fluorescence. UNIVERSITY ox SYDNEY. [Received September 4th 191 7 .

ISSN:0368-1645    

DOI:10.1039/CT9171100946

出版商:RSC    

年代:1917

数据来源: RSC

摘要:

952 BROWN AND ROBINSON VERATRICSULPHINIDE. LXXX I. - Veratricsulphinide. By JANET FORREST MCGILLIVRAY BROWN and ROBERT ROBINSON. BAKER and Smith (“A Research on the Pines of Australia,” Sydney 1910 p. 397) have shown that the ‘Huon Pine’ of Tae mania (Dacrydizcm Franklini) furnishes a leaf and a timber oil which consists chiefly of eugenyl methyl ether (I) and although very considerable quantities of the substance could be rendered available from this source there exists no outlet for the utilisa-tion of the compound. I n considering this matter it’ appeared that veratricsulphinide (11) possibly a non-toxic sweetening agent might be readily preparejd from the ether and we there-fore proceeded t o investigate this derivative of “ saccharin,” which it was found could readily be obtained by the oxidation of home veratrole-6-sulphonamide (111) by means of an alkaline solution of potassium permanganate.MeO/‘CH,*CH :CH2 MeO’)CO->N M~O/\CH, M ~ O I ISO,-NH, MeO(,SO \/ MeO( I (1.) (11- 1 (111.) (IV.) . Veratricsulphinide was found to have no sweet taste. Although veratrole and hornoveratrole react smoothly with chlorosulphonic acid and yield the corresponding sulphonyl chlorides in the cold and in quantitative amount a number of verat,role derivatives behave in a somewhat’ abnormal manner. Eugenyl methyl ether and safrole are converted into halogen-free neutral substances which are apparently sulphonic lactones The compound from eugenyl methyl ether crystallises from alcohol in leaflets meltin BROWN AND ROBINSON VERATRICSULPHINIDE.953 at 145O and the inve,stigation is being continued. Chlorosulphonic acid converted the nitrile of piperonylic acid into a dimeride t o which we' ascribe the constitution IT. E X P E R I M E N T A L . ~erc~trole-4-sulpholzyl Chloride. This substance has been prepared by Paul (Ber. 1906 39 2773) from veratrole-4-sulphonates. The following direct process is con-venient and the yield is quantitative. A solution of chloro-sulphonic acid (40 grams) in chloroform (120 grams) was gradu-ally added to veratrole (20 grams) when a vigorous reaction occurred. After allowing to remain duriiig an hour water was added and the chloroform solution dried and evaporated. The solid residue was sufficiently pure for most experiments but a portion was crystallised from a mixture of benzene and light petroleum and the colourless needles melted at 71'.The sulphonamide was also prepared and melted at 136' after crystallisation from alcohol. 5-n'it rouera trol e-4-sulphonyl Chloride, MeO/\NO, Me01 IS0,Cl- \/ Nitric acid (75 c.c. D 1-42) was added with cooling to vera-trolesulphonyl chloride (30 grams) and after an hour the mixture was poured into water and the nitro-derivative collected and crystallised from acetic acid. The pale yellow needles melted a t 128O : 0.1223 gave 0.0613 AgC1. C1=12.3. C8H80,NC1S requires CT = 12.5 per cent. When this substance (10 grams) was boiled with potassium hydroxide (10 grams) in water (100 c.c.) during a minute and a half i t dissolved t o an orange liquid which became yellow on neutralisation with hydrochloric acid.On cooling potassium nitroveratrolesulphonate separated almost completely as a bright yellow crystalline powder. This was washed with a little water and dried a t looo: 0.1355 gave 0.1006 BaSO,. S=10*4. 0.1635 , 0.0468 K2S04. K=12*8. C8H,0,NSK requires s = 10.6 ; I< = 13.0 per cent. On boiling with nitric acid this salt was converted into 4 5 -dinitroveratrole which is a proof that the constitution assigned to the nitroveratrolesulphonyl chloride is correct 954 BROWN AND ROBINSON VERATRICSULPHINIDE. 5-Nitroveratrol e-4-sulphonamide crystallised from alcohol in pale yellow needles melting a t 132O. 5-Aminoveratrole-4-sulphonic A cid, 31e(l/\NH . M~O!,,,,!SO,H Considerable quantities of this acid were required f o r some synthe-tical experiments and the following procedure was adopted after a number of trials.The yield was 78 per cent. of that demanded by theory and indeed the whole preparation of the substance from veratrole is a simple operation involving but smali loss of material. It was found best t o carry out the reduction on the scale described Hydrochloric acid (25 c.c.) was added to a mix-ture of potassium nitroveratrolesulphonate (5 grams) and crystal-lised stannous chloride (15 grams). Heat was developed the nitrosulphonate passed into solution and the aminosulphonic acid crystallised. Hot water (50 c.c.) was added and the mixture allowed t o cool after which the solid was collected and recrystal-lised by solution in hot aqueous sodium carbonate and reprecipita-tion by hydrochloric acid.The substance is sparingly soluble even in hot water and crystallises in small hard colourless prisms, which were dried a t 120° without suffering change in appearance: 0.1338 gave 0.1319 BaSO,. S=13.5. C,H,,O,NS requires S = 13.7 per cent. 0.1709 neutralised 0*0290 NaOH whereas this amount of a monobasic acid C8HI1O,NS requires 0.0293 NaOH. Like other derivatives of veratrylamine this substance develops an intense blue coloration with ferric chloride in aqueous solution. On addition of hydrochloric acid to a fairly concentrated solution of the amino-sulphonic acid in potassium carbonate to which rather more than a molecular proportion of sodium nitrite had been added the diazonium derivative is readily produced and separates in colourless crystals.This compound is doubtless of the type of diazobenzenesulphonic acid and is relatively stable. It couples with @-naphthol to a crimson azo-compound and retains this power even after boiling its aqueous solution for a short time. On adding potassium iodide to an aqueous suspension of the diazo-derivative nitrogen was evolved and the potassium salt of an iodosulphonic acid crystallised from the solution. When pure nitroveratrolesulphonyl chloride was employed in the preparation of the amineacid the substance described was the sole product isolated but on the other hand when the crude product was utilised without purification then the acid mother liquor fro BROWN AND ROBINSON VERATRICSULPHINIDE. 955 which the 5-aminoveratrole-4-sulphonic acid had been separated, slowly deposited long needles on keeping in the ice-chest.The substance is very probably 3-nminoverntrole-4-sulpho~aic acid and its formation is a proof of the presence of a sniall proportion of an isomeride in the product of the nitration of veratrolesulphonyl chloride. After recrystallisation from water colourless needles containing solvent of crystallisation were obtained and the analytical results were rather unsatisfactory until the material was dried a t 120°: 0.1310 gave 0.1299 BaSO,. S=13.6. C,H,,O,NS requires S = 13-7 per cent. This substance was produced in such small amount that a com-plete examination was impossible but it was found to be dis-tinguished from its isomeride by its greater solubility in water and by crystallising in needles instead of prisms.With ferric chloride it gives an orange coloration in aqueous solution. The substance appears to be oxidised by nitrous acid but with the aid of P-naphthol sufficient evidence of the presence of a primary amino-group was obt,ained. Homo v era trol e-6-sulp honamide (111). Homoveratrole (60 grams) was converted into the corresponding sulphonyl chloride by the action of chlorosulphonic acid exactly as described above f o r the preparation of vertatrolesulphonyl chloride but in this case the product was an oil which could not be crystallised. The substance was therefore converted into the sulphonamide by mixing with aqueous ammonia (250 c.c. D 0*88), when a vigorous reaction ensued and a colourless crystalline sub-stance was produced.This was coliected washed with water and recrystallised from alcohol and the yield obtained was 80 per cent. of that theoretically possible. The substance crystallised from alcohol in prismatic needles and from ethyl acetate in com-pact prisms melting at 191O: 0.1147 gave 0.1959 CO and 0.0584 H,O. 0.1215 , 0'1228 BaSO,. S=13.9. C,H,,O,NS requires C =46.7 ; H = 5.6 ; S = 13.9 per cent. This substance is far more sparingly soluble than veratrole-sulphonamide and advantage might possibly be taken of this in order to estimate the percentage of guaiacol in specimens of creosol. C=46*6; H=5*7 956 BROWN AND ROBINSON VERATRICSULPHINIDE. Veratric-6-sulphi~1ide '' Darnethoxysaccharin " (11). Homoveratrolesulphonamide (25 grams) dissolved in a solution of potassium hydroxide (10 grams) in water (500 c.c.) was oxidised a t 80° by t'he gradual addition of potassium permanganate ('70 grams) dissolved in hot water (850 c.c.).When all the perman-ganate was reduced the filtered solution was cooled and saturated with carbon dioxide when a sniall quantity of unchanged sulphon-amide was recovered. The liquid was evaporated until crystals began to separate from the hot solution which was then allowed to cool. The solid was collected and found to consist of a potassium salt which was accordingly dissolved in water and the solution acidified with hydrochloric acid. The colourless precipi-tate was collected and crystallised from much acetic acid. The substance was extremely sparingly soluble in most organic solvents and also in water.It dissolved however in boiling water t o some extent and separated on cooling in fern-like aggregates of needles : 0.1096 gave 0.1773 CO and 0.0375 H,O. 0.1338 , 0.1270 BaSO,. S=13.0. C,H,O,NS requires C = 44.4 ; H = 3.7 ; S = 13.2 per cent. The melting point of this compound is not sharp as i t com-mences t o soften a t 275O and is completely fused a t 290c. It is entirely devoid of sweet taste and is on the contrary, slightly acid and bitter. I t s acidic properties are well marked as it readily dissolved in cold aqueous sodium carbonate and even in warm sodium acetate solution. The sodium salt crystallises from water in glistening needles and has no sweet taste. The sub-stance is very stable towards alkali and even on fusion with potassium hydroxide there is little sign of decomposition.How-ever the methoxy-groups are so hydrolysed since on dissolving the fusion in water acidifying and extracting with ether the extract can be shown to contain a catechol derivative by the usual test although the intense bluish-green with ferric chloride and the Bordeaux-red obtained on the addition of sodium carbonate are far more charact'eristic than is the case with catechol itself. N-Methyl Bem'vatiue.-This substance is readily obtained by warming and shaking a solution of the sulphinide in aqueous sodium carbonate with methyl snlphate. It separates from the alkaline solution in colourless crystals and may be recrystallised from alcohol in which i t is sparingly soluble. I n appearance it resembles the mother substance and crystallises in fronds which are aggregates of needles melting at 227O: C=44*1; H=3.8 BROWN AND ROBINSON VERATRICSULPHINIDE.957 0.1209 gave 0.1106 BaSO,. S=12*6. C,,HllO,NS requires S = 12.5 per cent. The substance is insoluble in cold dilute aqueous potassium hydroxide but on boiling gradually passes into solution as the result of hydrolysis. On acidification there is no precipitate in the cold but on boiling the solution separation of N-methyl-veratricsulphinide occurs. The substance was collected and melted a t 227O. 2 3 6 7-Dimethylenetetraoxyanthraquinonedi-inaide (IV). The direct sulphochlorination of derivatives of veratric and piperonylic acids was investigated in the hope of discovering a convenient approach t o the substituted “ saccharins,” but the results were usually negative.The action of chlorosulphonic acid on the nitrile of piperonylic acid resulted however in the forma-tion of an anthraquinone derivative of a new type. The nitrile (5 grams) was dissolved in chloroform (15 c.c.) and chlorosulphonic acid (7 grams) gradaally added. The liquid became dark red heat was developed and after the initial reac-tion had subsided the mixture was heated on the steam-bath during one minute. It was then cooled and mixed with acetic acid when an orange-red substance separated which was collected and washed with ether. This substance appeared t o be a salt and was warmed with a solution of sodium acetate and so changed t o a nearly colourless flocculent precipitate which was collected, washed with water and dried and then crystallised from nitro-benzene and again several times from xylene.The clumps of colourless micrmcopic needles melted a t 2 6 1 O : 0.1208 gave 0.2891 CO and 0.0377 H,O. 0.1300 , 10.7 C.C. N a t ZOO and 765 rrim. N=9*6. C,,H,,O,N requires C = 65.3 ; H = 3.4 ; N = 9.5 per cent. The compound is very sparingly soluble and dissolves in sulphuric acid t o a rich crimson solution which becomes yellow on the addition of water. The solution resembles in colour-tone those which are obtained from methoxyanthraquinones and sulphuric acid and on this account and in view of the results of analysis the constitution suggested appears probable. Nevertheless only a mere trace of anthracene was obtained by boiling with hydriodic acid followed by distillation of the washed product over zinc dust in a stream of hydrogen. The amount obtained from 2 grams enabled us to recognise anthraquinone obtained on oxidation by the oxanthranol reaction. The substance appears t o be remark-ably resistant t o hydrolysis and is unchanged by boiling hydro-C=65.3; H=3*5 958 ROBINSON AND ROBINSON : chloric acid. Shonld opportunity offer the properties of this sub-stance and some analogous compounds which have been prepared, will be further investigated. UNIVERSITY OF SYDNEY. [Received September 4th 1917.

ISSN:0368-1645    

DOI:10.1039/CT9171100952

出版商:RSC    

年代:1917

数据来源: RSC

摘要:

958 ROBINSON AND ROBINSON : L X X X I I. -Re sea IT hes on Pseudo - bases. Pa? *t 11. Note o n some Beybering Derivatives and Remayks on the Mecharhszz of the Condensation Reactions o j Pseud o-bases. By GERTRUDE MAUD ROBINSON and ROBERT ROBINSON. THE analogy between berberine and cotarnine was spectro-chemically demonstrated by Tinkler (T. 1911 99 1340) and in view of the fact that the former base contains an unreduced isoquinoline nucleus it became of interest to examine its behaviour in connexion with the formation of condensation products analogous t o the numerous anhydrocotarnine derivatives. Anhydroberberineacetone (I) (+B-CH,*COMe) is the only sub-stance of this type which has been investigated. It was prepared by Gaze (Zeit. Nuturwiss. Halle 1890 62 399) and its analogy to anhydrocotarnineacetone was pointed out by Gadamer (Arch.Pharm. 1905 243 42) and confirmed by the examination of the substance which was made by Pyman (T. 1911 99 1694). 0-CH /\A I CH*OH(OEt) OH I I -+ A/\(7/\/ Me01 \ / \ / & \ / C H 2 I RN I f-Me0 CH CH2 I I CH,-COMe I CH -+ Y<OH(O I H ~ t ) RN*OH(OEt) +- li I (111.) * Part I (T. 1914,105 1456) contains the following errata on page 1458 : for 6-nitropiperonylhydrocotarnine read 6-nitropiperonoylhydrocotarnine and for anhydrocotarnine-6-nitroveratrole and 6-nitroveratrole read anh ydro-cotarnine- 6-nitrohornoneratrole and 6-nitrohornoveratrole respectively RESEARCHES ON PSEUDO-BASES. PART 11. 959 It was found in small-scale experiments that berberine condensed readily with alcohols amides such as carbamide phthalimide, 2-methylindole acetophenone 1-hydrindone cydohexanone nitro-methane 2 4-dinitrotoluene 2 4 6-trinitrotoluene diethyl malonate ethyl acetoacetate ethyl phenylacetate phenylaceto-nitrile and indene.Berberinol (compare Tinlder Zoc. c i t . ) was dissolved in alcohol and after the addition of one of the com-pounds mentioned the mixture was gently warmed. As a rule a sparingly soluble substance separated often in a viscid condition, but crystallisable after treatment usually by washing with alcohol and the derivatives were lemon-yellow with the exception of the nitro-compounds which were orange or red. All the sub-stances were resolved into their components by acids and anhydro-berberine derivatives are therefore much less stable than the corre-sponding substances obtained from cotarnine or hydrastinine.Circumstances forced the authors to abandon the detailed examina-tion of these substances a t a time when the work had not pro-ceeded far and was quite incomplete but it nevertheless now seems desirable to record the results of the investigation. Cyano-dihydroberberine ($-B-CN) methoxydihydroberberine ($-B-OMe), anhydroberberineacetophenone ($-B-CH,*COPh) and anhydro-berberinenitromethane ($-B-CH,*NO,) are de-scribed in the experi-mental portion of the paper. The Mechanism of Pseudo-base Condensation. The fact that berberine resembles cotarnine in its reactions emphasises the probability that the reactive modification is in each case the quaternary ammonium hydroxide form since berberine has an even greater tendency than cotarnine to assume this unsaturated condition.The formation of anhydroberherine-acetone was found to occur in dilute alcoholic solution under con-ditions not favourable to the existence of berberinol and a hitherto unrecorded observation on the condensation of cotarnine with nitromethane may also be cited. A dilute aqueous acetic acid solution of cotarnine was mixed with nitromethane and on the addition of sodium acetate the condensation product was formed slowly in the cold rapidly OM heating t h O mixture and the substance was identified with anhydrocotarninenitromethane (Hope and Robinson T. 1911 99 2119). I n this acid solution the presence of the carbinol form of cotarnine is extremely improb-able.A t the same time condensation products are obtained from cotarnine and berberine under conditions which do not favour electrolytic dissociation of an ammonium hydroxide. Thus the presence of an excess of sodium hydroxide does not appear t 960 ROBINSON AND ROBINSON : inhibit the reactions. A representation of the mechanism of the Knoevenagel reaction based on the assumption of a reaction between ions was suggested by Lapworth (Hope and Robinson, Zoc. c i t . 2117) and was a great advance on the ideas existing a t that time especially as it facilitated the collation of data derived from such separate investigations as those of Knoevenagel on the use of amines particularly secondary amines as catalysts in con-densations of Dobbie Lauder and Tinkler on the spectrochemistry of pseudo-bases and of numerous workers on the chemistry of these substances.These advantages are secured by the recogni-tion that the reactive form of a carbinol-amine (11) is the un-saturated ammonium hydroxide (111) but instead of representing the further stages as due to ionisation combination of the ion with a negative residue and finally migration the present authors prefer to regard the condensations as due to a simple addition of the components as illustrated in the scheme : “”-% ....... fi c_) I fH*+ NR I I n the case of a condensation between a pseudo-base and pseudo-acid the theory of the reaction between ions demands two intra-molecular changes but on the hypothesis now advanced the carbon to carbon synthesis occurs in the first stage of the process and migrations are not required.This is illustrated in the case of anhydrocotarninenitromethane and it will be seen that the mi-modification of nitromethane and the ammonium hydroxide form of cotarnine yield a complex (IV) in which there may be a change in affinity dist’ribution which results in the separation of water and the production of anhydrocotarninenitromethane. (IV.) The essential feature of these representations is the postulation of conjugated partial dissociation as a preliminary stage od th RESEARCHES ON PSEUDO-BASES. PART 11. 961 reactions and this is a particular case of the process described by Baly as "opening up the molecular force fields." The mode of expression is however slightly differentl from that employed in it former communicat-ion (T.1916 109 1031 * e t seq. 1042). Taking methyl iodide as an example then in reactions in which the iodine becomes separated from the methyl group it is assumed that there is a partial dissociation and that the reactive molecule should be represented as . . . CH,I.. . . The present suggestion is merely that the partial valency so expressed shall be considered to be derived from the normal valencies and that the dissociation necessarily weakens the bond between the carbon and iodine atoms, so that the complete symbol is ... CH ... I... . Where a partial dissociation can be followed by complete electrolytic dissociation, there is a clue t o the polarity of the partial valencies since it may reasonably be assumed that the partial dissociation is a stage in the complete process.Further it is clear that the partial dis-sociation of latent valencies must be assumed in some cases 88, for exzmple in the combination of ammonia with hydrochloric acid : The conjugated partial dissociation of such an ammonium hydroxide as cotarninium hydroxide is a more complex example of the same kind: * In this paper the residual affinity was regardcd as additional to the I ormal valency not as a part of the latter. The theory of the reactions is not fundamentally altered and in accordance with the suggested method of expression the addition of an alkyl haloid to an unsaturated base would be represented by the scheme 962 ROBINSON AND ROBINSON : I n partial dissociation of latent valencies two partial valencies of opposite sign become available and these emanate from the same atom whereas when a normal valency is divided the two parts will be of the same sign so that the ring in IV in regard to the polarity of the partial valencies should be expressed as shown below: The logical application of schemes of partial dissociation simple and conjugated of addition and decomposition by making and breaking of partial valencies and of redistribution of affinity, demands the consideration of these questions of polarity and leads to a system of mechanism of reactions which appears to be capable of including the representation of chemical changes of the most varied type and the present authors are not acquainted with ally examples of reactions the course of mhich cannot be illustrated in the manner implied.It is true that the subdivision of units invariably supplies greater facilities for explanations but in the present instance there is the important restriction on the elasticity of the theory which is imposed by the necessity of providing the reactive complexes with two free partial valencies of opposite sign and this has introduced no difficulty in any case examined. I n order t o avoid possible misapprehension it should be stated that reactions between ions are not excluded but regarded as the limiting case and further that it is recognised that the symbols which are used to express the activated condition of molecules can represent only a first approximation to the actual distribution of affinity. We cannot deal with every instance in which it is imagined that the method of representation advocated has clear advantages in the summarisation of the experimental data and we therefore confine ourselves t o two reactions which have been the subject of comparatively recent controversy.The Bromination of Ketones. Lapworth's theory of the mechanism of the bromination of acetone and other ketones (T. 1904 85 30) has received much support from subsequent experimental work and i t may be said to be universally accepted that the essential reaction is the addi-tion of bromine to the enolic form of the ketone. Leuchs (Ber. RESEARCHES ON PSEUDO-BASES. PART 11. 963 1913 46 2435) however brominated optically active o-carboxy-2-benzyl-1-hydrindone and obtained 5-10 per cent.of an optically active bromo-derivative and since the enolic form of this ketone contains no asymmetric carbon atom it was claimed that the bromiaation was in part a direct substitution. I n accordance with the theory of partial conjugated dissociation of an enol however, the actual reactive conditions is not .... ! . . ‘ . . . . and this reactive form is seen to be intermediate as regazds its distribution of affinity between the ketone and its enolic modifi-cation. Consequently the catalytic action of hydrobromic acid on the ketone in producing the enol will involve the reactive form of the latter as an intermediate stage. I n this molecule the partial valency preserves the asymmetric environment of the carbon atom and the formation of an optically active bromo-derivative is therefore possible.The whole process may be repre-sented in the following manner: . . iWec ha n i s m of Dicrz o-coupling . K. H. Meyer (compare “Annual Reports,” 1914 11 100; 1915, 12 115) and his co-workers hold the view that diazo-coupling is due to an addition of the diazonium salt to a double bond or conjugated double bond in the second component. Other authors, as Auwers and Michaelis and Karrer (loc. c i t . ) are of the opinion that the reaction is in the first place one of addition t o the oxygen or nitrogen atom of the phenol or amine and that this is followed by migration. Both these views are experiinentaIly founded and a t present regarded as contradictory. The application of the theory of addition of partly dissociated coinplexes leads t o a representation which in the present authors’ opinion explains the whole of the facts including those relating t o the chemistry of the diazonium salts themselves.It has already been suggested (T., VOL. UXT. P 964 ROBINSON AND ROBINSON 1916 109; 1042) that the characteristic reactions of aromatic amines and phenols must be ascribed to additions t o a conjugated unsaturated system which includes the nitrogen or oxygen atoms. The neutral and reactive phases of a phenol such as m-cresol will therefore be the following : An examination of the polar properties of the partial valencies shows that the orientation rules are a direct consequence of the opposite sign of the latent valencies of elements such as oxygeii and nitrogen but it must be remembered that in dealing with amines and phenols the effects observed are considerable and well defined and that in connexion with the general problem of orientation in the benzene ring it may be necessary t o take cognisance of even more delicate influences than the conjugation of partial valencies.The reactive phases of an aromatic amine will correspond with those figured above in the case of m-cresol. Addition to the unconjugated reactive inodifications will involve the attachmentl of a group to the oxygen or nitrogen atoms, whereas addition t o the molecule in its conjugated dissociated condition will involve nuclear substitution. I F the former reac-tion is reversible and this is usually the case there may ensue an apparent transference of a group from oxygen or nitrogen to the nucleus and the transformation of diazoamino-compounds into true azo-derivatives is not improbably a reaction of this type.The phenomenon is analogous t o that involved in the productio RESEARCHES ON PSZlUDO-BASES. PART 11. 965 of mesidine from phenyltrimethylammonium chloride and as this is a simpler case the first stage of the process may be illustrated: The last reaction is a conjugated decomposition that is the reverse of addition t o a conjugated system. Such reactions are of great importance in the aromatic series and there appears to be no valid reason why the decomposition should have a more complex mechanism than the formation of the additive product. Turning to the diazonium compounds it' must be noted that these substances (for example hydroxides) are in constitution and properties strikingly analogous t o such substances as cotarninium hydroxide and owe their reactivity t o a similar partial decom-position which is expressed in V.Addition between the reactive phases of a phenol and of a diazonium hydroxide will result in VI and possibly VII may then be obtained by a redistribution of affinity, (V. 1 (VI-) (VII.) VII is clearly the oxoniuin hydrate of the keto-form of an azo-phenol but it is also the hyd_rate by conjugated addit,ion of the enolic modification and the latter may be obtained by conjugated decomposition as shown above for the precisely similar conversion of a ketone into an enol with the aid of hydrobromic acid. It should be pointed out however that i t is unnecessary to go so far as VII in rearranging the affinity of VI.If for example, the partial valency connecting the nitrogen atoms is broken the nat,ural result of the activity of the free partial valencies is indicated in VIII IX and X. P P 966 ROBINSON AND ROBINSON : The above will apply t o a phenol such as &naphthol which couples in the ortho-position. Para-substitution will involve the inclusion of an additional double bond in the conjugated system, and it is clear that the scheme is applicable to amines as well as to phenols. .... I . . . .*. .. . . I.. . . . . 0 (VIII.) E X P E R I M E N T A L . Cyanodihydrob erb epine. This substance was prepared by Henry (Annnlen 1860 115, 136) and regarded as a sparingly soluble salt which crystallised from alcohol in yellow rhombic leaflets.The analysis given is 3 per cent. lower than the theory and indeed a t that time the composition of berberine was supposed to be C,2H,,010N (C= 6 ; 0 = 8 ) . I n 1872 Fliickiger (Jahresber. 748) stated that the sub-stance did not exist, and later Pommerehne (Arch. Pharm. 1895, 233 127) reaffirmed that berberine forms a stable hydrocyanide. l'inkler (Zoc. cit.) used the substance in connexion with his spectro-chemical work. Since i t appears that this compound has not yet been accurately analysed or described we prepared a specimen by adding potassium cyanide to a solution of berberine sulphate until the yellow colour disappeared. The solid was collected and rapidly crystallised from alcohol and then from benzene in which the substance is sparingly soluble.It was found necessary t o keep the solution in the dark as the compound is decomposed by light. The pale yellow prisms melted a t 184-186O when somewhat rapidly heated : 0.1405 gave 0.3602 CO and 0.0661 H,O. C,,H,,O,N requires C = 69.6 ; H = 5.2 per cent. The substance is readily soluble in chloroform and sparingly so in ethyl acetate from which i t crystallises in yellow octahedra. It is stable towards aqueous potassium hydroxide and is not immediately decomposed by cold dilute hydrochloric acid. On gently warming hydrocyanic acid and loerberine chloride were C=69*9; H=5*0 RESEARCHES ON PSEUDO-BASES. PART 11. 967 produced. No definite evidence of the formation of a salt of the base was obtained but that substances of this type are real bases which can form salts without decomposition is evident from the behaviour of cyanohydrocotarnine.This substance dissolves in dilute sulphuric acid but on scratching the container colourless crystals of a sparingly soluble sulphate separate. Only on heat-ing does the colourless solution become yellow and hydrocyanic acid is then set free. It is a mistake therefore to term these substances pseudo-salts. They are in no sense salts but bases which can combine with acids and in this condition ar9 readily decomposable. We have also observed that cyanohydrocotarnine forms a methiodide. Me t h ox ydi hgdro h erb e rin e J/-B-O Me . Perhaps the most characteristic reaction of pseudo-bases is the formation of ethers of the carbinol form by simple treatment with alcohols and i t is interesting to note that this property is exhibited not only by the rosaniline bases but also by many t’ri-phenylcarbinol derivatives not containing nitrogen and by the xanthhydrols and other pseudo-oxonium bases.I n the presence of excess of water these ethers are as readily hydrolysed as they were formed and the conclusion to be drawn from the whole matter seems to be that the interconversion of the two forms of the pseudo-base is accomplished by addition and subtraction of water or of an alcohol. Gaze in a private communication to Beilstein’s I ‘ Handbuch,” states that berberine yields an alcoholate, C,,,H,,0,N,C2H,0 which he describes as golden crystals but there appear to be no further references in the literature to substancss of this type.Berberinol (15 grams) was added with stirring to methyl alcohol (35 grams) when the substance became more crystalline in appearance. After remaining during two hours the substance was collected and rapidly crystallised from methyl alcohol. It was obtained in pale yellow prisms melting a t 1 5 2 O : C,lH,,O,N requires @= 68.7; H=5.7 per cent. 0.1239 gave 0.3126 CO and 0.0661 H20. I n attempting to crystallise this substance from ethyl acetate, oxyberberine melting at 198 -ZOOo was obtained. The substance was also readily changed to osyberberine by boiling with sodium methoxide in methyl-alcoholic solution. It appears to be more easily oxidised than berberiiiol itself Like most dihydroberberine derivatives the dilute solution in ethyl acetate exhibits blue fluorescence.The methoxy-group was readily removed in the four Qf methyl alcohol on warming the substslice with water, C=68*8; H=5*9 968 RESEARCHES ON PSEUDO-BASES. PART 11. Ethoxycli~iydroberberine.-This derivative crystallised in golden-yellow rectangular prisms which darken a t 125O and melt a t 1 3 6 O . Its properties were similar t o those of the methoxy-compound. In absolute ethyl alcohol the substance condensed readily with acetone producing anhydroberberineacetone melting at 175O. isoAntyloxydihydro b erb wine.-This substance was obtained in circular clusters of golden needles and melted a t 157O. Its ethyl acetate solution exhibits blue fluorescence. ,4 qihydrob er b erineacetophei~one $-B-CH,*COPh.This derivative was obtained by condensing berbetinol with acetophenone in alcoholic solution or by starting with methoxydi-hydroberberine and carrying out the reaction in absolute methyl-alcoholic solution. It' is however more convenient t o operate in the following manner. Berberine sulphate (20 grams) was mixed with alcohol (100 c.c.) and acetophenone (10 grams) and after gently heating the mixture a 20 per cent. aqueous solution of potassium hydroxide was added until the orange colour became red and then yellow. The liquid wa5 vigorously stirred and after the addition of water the yellow oil gradually solidified and was collected and crystallised first from alcohol in which the sub-stance is sparingly soluble and then from ethyl acetate. The final purification was by crystallisation from benzene containing a little light petroleum and the substance was then obtained in bright yellow prisms melting at 140-141O : 0.1310 gave 0.3542 CO and 0-0658 H,O.C28H2,0,N requires C = 73.8 ; H = 5.5 per cent. This compound is a t once decomposed by acids yielding a berberine salt and acetophenone the odour of which is perceptible even when the compound is warmed with water. The substance was changed by methyl sulphate into' what appeared t o be a mix-ture of metho-salts with berberinium sulphate. 011 boiling the golden-yellow mixture with hydrochloric acid acetophenone was liberated and a salt separated which had the appearance of berberinium chloride but was coiitaminated with a considerable proportion of some analogous compound.The mixture could not be separated into its constituents hut analysis indicated that it consisted of berberinium chloride and a methylberberinium chloride. C=73'7; H=5.6. A I I Jiy1rob erb frill P ) L it row Ptlicoi e $-R-CH,*NO,. Berberine sulphsts (20 grams) was warmed with a mixture of ethyl alcohol (100 c.c.) and water (100 c.c.) and treated with MEEK THE ABSORPTION SPECTRA ETC. 969 concentrated solution of potassium hydroxide until a clear solu-tion was obtained. Nitrornethane (10 c.c.) was then added and more dilute potassium hydroxide gradually introduced care being taken not t o render the solution strorigly alkaline. A crystalline, red precipitate was formed which was collected and recrystallised from alcohol. The orange-red needles melted a t 140'. Recrystal-lisation from alcohol resulted in lowering of the melting point to 136O but from toluene orange prismatic needles melting a t 1 4 2 O were obtained : 0.1165 gave 0.2733 CO and 0.0582 H,O. C=63*9; H=5*5. This substance is changed by acids into a berberine salt. C,lH,,O,N requires C = 63.6 ; H = 5.1 per cent. It was also obtained by condensation of methoxydihydroberberine and nitromethane in methyl-alcoholic solution. UNIVERSITIES OF SYDNEY AND LIVERPOOL. [Received September 4th 1917.

ISSN:0368-1645    

DOI:10.1039/CT9171100958

出版商:RSC    

年代:1917

数据来源: RSC

摘要:

MEEK THE ABSORPTION SPECTRA ETC. 969 L X X X I I I . - T h e Absorption Spectra of some Polyhydroxy-an thr.aquinone Dges in Concentrated Sulphwic Acid Solution and in the S t a t e of Vupour. By DAVID B. MEEK. IN a previous communication (Meek and Watson T. 1916 109, 544 e t seq.) on the colour of the polyhydroxyanthraquinone dyes i t was shown that the wave-length of the maximum of an absorp-tion band of any of the substances depended orL whether the sub-stance was examined in alcoholic solution in potassium hydroxide solution or on cloth variously mordanted. Taking the absorp-tion as due to the resonance produced in a system capable of oscillating between the different tautomeric forms then this period of oscillation was regarded as modified by the nature of the radicle attached to the conjugate chain of double and single bonds.One of the conclusions drawn from that investigatdon was that “the more electropositive the nature of the radicle attached to a con-jugate chain the longer will be the wave-length of the maximum of the absorption band.” I n that work the spectrum of each of the dyes was examined (1) in alcoholic solution (2) in aqueous potassium hydroxide solution and on wool inordaiited with (3) tin, (4) alum and (5) chrome respectively. The present investigation was undertaken with a view t o obtain information regarding th 970 MEEK THE ABSORPTION SPECTRA OF SOME absorption spectra of the same polyhydroxyanthraquinone dyes in solution in concentrated sulphuric acid and in the state of vapour. Some of these dyes had given a number of fairly narrow sharp bands in alcoholic solution (Zoc.cit.) and i t seemed of importance to discover whether under other conditions the narrow bands which had been obtained could be broken up into absorption lines, for as a vapour a t atmospheric pressure iodine has very fine absorption lines whilst in solution i t gives absorption bands which are broader than those yielded by some of the polyhydroxyanthra-quinone dyes. The difficulty of obtaining the absorption spectra of many organic substances as vapour is that they frequently decompose before vaporising and hence the absorption spectra have to be observed when the dyes are vaporised at low pressures. With the same end in view namely of obtaining very narrow absorption bands one of the substances alizarin-cyanine which gave narrow bands in alcoholic solution was also examined in a number of organic solvents.It may be stated here that i t has not been found possible t o resolve any of the bands given by the polyhydroxyanthraquinone dyes into absorption lines but absorption curves havo been obtained which on resolution into elementary symmetrical bands have yielded further information regarding the effect of the number and position of auxochromes on the absorption and there-for0 on colour. E X P E R I M E N TAL. The absorption spectra of the dyes in concentrated sulphuric acid and of alizarin-cyanine in the various organic solvents were obtained in a manner similar to that described in the previous paper (Zoc. c i t . ) the apparatus being a Nutting photometer in combination with a large Hilger wave-length spectrometer.I n obtaining the positions of the absorption bands in the case of the vapours a slightly modified procedure was adopted. A brass tube 50 cm. in length and 1.5 cm. in diameter was fitted with air-tight caps taken from a polarimeter tube. The portion of these caps which is generally fixed to the glass polarimeter tube by means of hard wax was brazed t o the ends of the brass tube. They were then ground plane and by means of asbestos washers the caps could be made air-tight when screwed on firmly. Attached t o the side of the brass tube was a small brass tube through which the pressure inside the long brass tube could be reduced. To observe the absorption spectrum of the vapour of one of the dyes a small quantity of the substance was placed in a porce-lain boat and introduced into t h e brass tube.The polarimete POLYHYDROXYANTHRAQUINONE DYES ETC. 971 tube cap was then firmly screwed on and the whole tube placed in a resistance electrical furnace. The latter was larger than the brass tube and so the ends were well within the furnace. This prevented the deposition of the vaporised substance on the glass ends of the tube. The side-tube projected beyond the furnace and was attached to a Gaede pump by means of which the pressure inside the absorption tube could be reduced. The furnace was arranged so that a parallel beam of light could be passed through the absorption tube to one aperture of the photometer and another beam from the same source was brought by reflections to the other aperture.This method should have given measurements from which absorption curves could have been drawn but the difficulty of keeping the amount of vapour in the tube constant has not yet been overcome with the result that only the wave-lengths of the maxima of absorption have been determined up to the present. Although the absorption curves have not been obtained yet for the substances in the form of vapour an attempt has been made to classify the absorption bands according t o apparent intensity. The following table contains the results which have been obtained: TABLE I. Wavo-lengths of Comparative intensity Substance in the form of maxima of of these maxima of vapour mixed with air. absorption.absorption. (1) 5137 Very faint ( 2 ) 5040 Intense Intense ( 5 ) 4736 Very faint (6) 4635 Extremely faint Quinizarin or 1 4-dihydroxy-anthraquinone (fluorescent) Faint Purpurin for 1 2 4-trihy-droxyanthraquinone ( 1 ) 5256 Intense (2) 5045 Intense (3) Broad band of Intense general absorp-tion from violet upwards to about 4900 ( ( 1 ) 5135 ( 2 j 5050 Alizarin-Bordeaux or 1 2 5 8-tetrahydroxyanthraquinone [(5j 4693 Intense Intense Faint Very faint Extremely faint These absorption bands have been shown in Figs. 2 3 and 5 as straight lines drawn a t the wave-lengths of maximum absorption and of length varying according to the qualitative classification of intensity in the third column of Table I. It is interesting that the bands of quinizarin and Alizarin-Bordeaux vapours are closer P P 972 MEEK THE ABSORPTION SPECTRA OF SOME together than the bands of these substances in solution in alcohol, and it is also noteworthy that the differences between successive maxima of absorption of the substances as vapours are of the same order of magnitude as the differences between the successive maxima for alizarin-cyanine and anthracene-blue in alcoholic solution.The absorption clue t o the vapours of the other five FIG. 1. Wave-lengths. F I G . 2. 0 - -d4 * *m m m w (0 wdr * * m m m w w c o b 0 0 0 0 0 0 0 8 dr 0 0 0 d4 m o * 0 0 0 d4 0 0 0 d4 a30 * 0 0 0 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 5 0.4 .z 0.2 O a f c: 0 1.8 *s 1.6 2 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 0 dr 0 0 0 * 0 0 0 * 0 0 0 * 0 0 0 dr 0 0 0 * 0 0 0 0 dr -0 u3 m o w w o * *o m u 3 0 w w o 0 t- 0 * 0 dr 0 co 0 m 0 W 0 m FIG.3. Wave-lengths. FIG. 4. _ _ _ _ - _ Elementary synzmetrical curves. polyhydroxyaiithraquinones considered here was not resolved into narrow bands. Alizarin vapour gave geii era1 absorption coming up from the violet end of the spectrum as the density of the vapour was increased. Anthragallol gave a similar result whilst anthracen+blue gave a broad indistinct weak band with its centre about h = 5000 POLYHYDROXYANTHRAQUINONE DYES ETC. 973 The Absorption Spectra of the PolyJ~ydroxyantl~ru~~~i?~ones iijh Conceiztrated Sulphuric A cid Solutions. Solutions of strength AT/ 1.04 in concentrated sulphuric acid were prepared and examined by the Nutting spectrophotometer in the manner previously described (Zoc.cit.). The absorption curves obtained are given in Figs. 1 t o 8. FIG. 5 . Wave-lengths. FIG. 6. 0 0 0 0 0 0 0 8 G - 4 -2 * O - 8 -6 5 .4 .f .2 % 8 P .+ - 8 . G 2 T *8 - 6 .2 IIvrrrlrrllllllllllrlII11IY1I 0.0 > * 0 0 0 dc 0 0 0 * 0 0 0 dc 0 0 0 bi 0 0 0 dr 00d ) * * g LC m 0 (0 (90 bi dco 10 m o (0 c D 0 > 0 I u3 CD t- 0 cD 0 u3 0 cr 0 FIG. 7. Wace-lengths. FIG. 8. (1) Alizarin.-In potassium hydroxide solution there are dis-tinctly three bands the middle one being the most intense. I n concentrated sulphuric acid solution there are indications that these bands still exist but the middle one and the one towards the red have diminished in relative intensity .and probably also P P" 974 MEEK THE ABSORPTION SPECTRA OF SOME have broadened.The one towards the violet end has becoine relatively more intense. (2) &fri)?imrin.-The results are given in Table 11. TABLE 11. Wave -lengths of maxima Solvent,. A. (3) 4926 (4j 4815 (5) 4736 (6) 4635 Vapour (1) 5150 (2) 5018 ( 3 ) 4780 Alcohol (1) 5470 (1) 5944 Potassium (2) 5526 f=l/X. A(l/h) 194G 38 1954 47 2031 46 2077 34 2111 47 2158 -1942 51 1993 99 1828 139 1967 126 1683 127 1810 128 2092 -2093 -1938 -Relative order of intensity. 3 2 1 1 2 3 1 almost 2} equal 3 Remarks. (4) - (1) = 131 ( 5 ) - (2) = 127 (6) - (3) = 127 The absorption spectra of quinizarin in alcohol and as a vapour have the absorption over the same area of the spectrum as regards both extent and position.I n the concentrated sulphuric acid solu-tion and in the potassium hydroxide solution the areas of absorp-tion are larger but again almost equal and they have been shifted towards the red end of the spectrum the shift being greater in the case of the alkali solution. (3) Yrrrpurin.-The results are given in Table 111. TABLE 111. Wave-lengths of maxima Relative order Solvent,. A. f= 1/A. A( 1 /A). of intensity. Remarks. (1) 5256 1903 79 (l)'\about -(2) 5045 1982 59? (2)j equal -(3) Broad 2041? - - -band of general ab-s o r p t i o n from violet up t o about 4900 (1) 5524 1811 110 4 (2) 5205 1921 123 1 (3) 4892 2044 48? 2 (4) 4780? 2092? - 3 (1) 5564 1798 141 2 hydroxide \(2) 5113 1956 - 1 1 2 I Vapour Alcohol Sulphuric acid { (2) 5155 1939 -Potassium j(1) 5450 1835 12 POLY HYDROXY ANTHRAQUINONE 1) Y E S ETC.975 Again in the case of purpurin the absorptions by the vapour and by the alcoholic solutions occupy almost identical parts of the spectrum but as in quinizarin the absorption maxima are closer together for the vapour t,han for the solution in alcohol. With concentrated sulphuric acid and potassium hydroxide solutions the absorption has been displaced towards the red and the maxima f o r sulphuric acid solution are nearer the red end of the spectrum than the maxima for the alkali solution. (4) L4 nthwrycrlZol.-Iii the sulphuric acid solution there are three bands giving maximum absorption at wave-lengths 5750 5240 and 4620 and as regards intensity these are in the order 3 2 1 respectively.These three bands are not apparent in the potassium hydroxide solution as distinct bands but their existence as broad bands may be inferred from the shape of the absorption curve of the potassium hydroxide solution. One effect of the sulphuric acid has been t o render the resolution better and t o increase the relative intensity of the absorption towards the violet^ end of the spectrum. (5) A Ziza?.in-Bor~ZeaziIL:.--The results are given ii-i Table IV. TABLE IV. Wave -lengths of maxima Relative order Solvent. A. j=l/x. A(l/h). of intensity. (1) 5135 1947 33 Intense (2) 5050 1980 62 Intense (3) 4896 2042 30 Faint (4) 4805 2081 50 Veryfaiiit (5) 4693 2131 - Extremely faint {);; mi? 1'309? '19? 2 2128 - 1 (1) 6400 1663 181 4 (2) 5732 1744 143 1 Sulphuric acid (3) 5300 1887 10'3 2 (4) 5010 1096 - 3 i Vapour Alcohol 2 1 i Potassium (( 1) 6045 1655 115 hydroxide ( ( 2 ) 5650 1770 -Comparing the absorption in the state of vapour tion in alcohol the maximum of absorption is nearer the violet for the alcohol solution than for the vapowr.I n the state of vapour the bands are narrower and the resolution much better. For sulphuric acid and potassium hydroxide solutions the absorp-tion has been displaced towards the red and in the two solutions it occupies the same part of the spectrum. The sulphuric acid solution gives better resolution on the blue side of the absorptio 976 MEEK THE ABSORPTION SPECTRA OF SOME curve whereas the pot'assium hydroxide solution gives better resolution on the red side.(6) Alizarin-cyanine.-Table V contains the results for alizarin-cyan me. TABLE V. X-for ( 1 ) 5630 (4) 5085 ( 5 ) 4978 I (6) 4776 Solvent. maximum. (2) 5473 (3) 5337 Alcohol Relative order f = 1 /A. A( 1 /A). of intensity. Remarks. 1776 51 3 1827 47 1 f - f = 1874 92 2 (2) (4) 130 1966 43 4 2009 80 5 2098 - 6 (1) 6332 1580 76 3 (2) 6040 1656 137 1 (3) 5575 1793 183 2 (4) 5060? 1976 - 4 Potassium hydroxide Gradually r i s i n g curve from violet to red. No maximum b e t w e e n 4000 and I 7000 From table V and also from the curves it is again obvious that the absorption has been displaced towards the red in the con-centrated sulphuric acid solution and still further towards the red in the potassium hydroxide solution.The band which has been numbered (3) in the alcoholic solution has been masked in the sulphuric acid solution by the intensity of band (a) so that the bands (l) (2) (3) and (4) in sulphuric acid solution correspond with the bands (l) (a) (4) and (6) in the alcoholic solution. The band (2) in both solutions is the most intense and i t is also prob-able that the position of the maximum of absorption is not very much removed from the centre of the absorption band so we may obtain the displacement towards the red in the concentrated sulphuric acid solution by comparing band number (2) in alcohol with band number (2) in sulphuric acid.These bands we may take a t h=5473 and 6040 giving a displacement of 567 Angstriim units towards red. I n frequencies the figures are f=l827 and 1656 with a displacement of 171. Anthracene-bZwc TV,R.-Table VI gives the results for anthra-cene-blue POLYHY DROXYANTIIRAQUINONE DYES ETC. 977 X .for (1) 5655 (2) 5487 Solvent. maximum. Alcohol (6) 4875? TABLE VI. Relative order f = 1/X. A( 1 /A). of intensity. Remarks. 1768 55 -1823 47 - f - f = 1870 05 - (4) (2) 142 1965 37 _- f - f = 2002 49 - (5) (3) 132 - 2051 -Gradually rising curve from violet to red with an inflect.ioi1 a t about 5450 which shows that the curve is not a single absorption band. Potassium hydroxide Again the effect of the sulphuric acid and of the potassium hydroxide is to displace the absorption towards the red and the displacement due to the sulphuric acid is not so great as that due t o the potassium hydroxide.The resolution is also much better in the solution in sulphuric acid. Alizarin-cyanin e in Various Solvents. The absorption spectra of alizarin-cyanine in various solvents have been examined and the curves are given in Figs. 9 and 10. The results are also contained in table VII. Alizarin-cyanine was chosen for the purpose on account of the large number of narrow bands i t gives in solution in many organic solvents and the ease with which corresponding bands can be identified in the various solutions. From Table VII and also from Figs. 9 etc. it will be seen that the absorption bands can be recognised quite easily when dis-placed by the various solvents.The bands have been given dis-tinguishing letters - 3 1 3 c' etc. The last column of Table VII contains the refractive indices of the various solvents for sodium light. According to Kundt's law the greater the refractive index of the solvent the greater should be the displacement towards the red. I n many cases there is dis-placement towards the red but this is not always accompanied by an increase in the refractive index of the solvent. Looking a t the graph of wave-lengths of maxima of absorption against refractive indices of solvents (Fig. 12) we see that if the solvents of acid and basic nature are omitted chloroform is the d y solvent of those considered which violates Kundt's law t o a This is however not the case TABLE VII.Alizarin-cyanine in Various Solvents. Wave-lengths and frequencies ,4. B. C. D. E. F. Q. - 5589 5460 5330 5214 5086 4970 - 1789 1832 1876 1918 1967 2012 - 43 44 42 49 45 Solvent. Ether ........................... Amy1 alcohol .................. Chloroform ..................... Acetone ........................ Methyl alcohol ................ - 5599 5483 5346 5217 5100 4992 - 1786 1824 1871 1916 1961 2003 - 38 47 45 45 42 5726 5576 5432 5311 5173 5058 4960 1746 1793 1841 1883 1933 1977 2016 37 48 42 50 44 39 - - 5458 5324 5195 5083 4962 - - 1832 1879 1925 1968 2015 47 46 43 47 - -5558 5441 5313 5178 5065 4961 - 1799 1838 1882 1931 1974 2016 - 39 44 49 43 4 TABLE VII. (continued). Alizarin-cyanine id Various Solvents.Wave-lengths and frequencies A . B . C . D . E . F . G. I 5568 5436 5308 5186 5058 4952 - 1796 1840 1884 1929 1977 2019 - 44 44 4.5 48 42 Solvent. Glacial acetic acid x Pyridine ........................ Amy1 ether ..................... ........................ ra Anisole Phenol ........................ 13 Nitrobenzene .................. - 5545 5422 5286 5159 5028 4913 - 41 48 47 50 47 1803 1844 1892 1939 1989 2036 -5708 5608 5478 5346 5223 5102 4986 32 43 45 44 47 45 1752 1784 1827 1872 1916 1963 2008 - 5643 5512 5362 5227 5113 5000 - 1772 1816 1865 1913 1956 2000 - 44 49 48 43 44 5483 5375 - 5115 5005 - -- - 1822 1860 - 1956 1998 - - 38 96 42 1722 1772 1815 1873 1913 - 2007 1722 1772 1815 1873 1913 - 2007 50 43 58 40 9 980 MEEK THE ABSORPTION SPECTRA OF SOME 1.4-1.3 1.2 1.1 1.0 0.9 i u Ei 0.8 * * g3 S 0.7 E -* u 0.6-v) rQ 9 0.5 0.4 0-3 0.2 0.1 large extent.Neglecting pyridine acetic acid and phenol there is a general tendency to displacement towxds the larger wave-length with increase of refractive index but the nature of the ------------O k FIG. 9. 45 47 ~-51 53 55 57 59 61 solvent as regards acidity or basicity certainly has an effect on the displacement of the absorption bands. The displacements cannot be due t o absorption bands in th POLYHYDROXYANTHRAQUINONE DYES ETC. 981 infra-red of the spectra of the solvents for the absorption con-sidered is that of the solution less that of the solvent,.So far as the effect of solvent on the colour of the polyhydroxy-anthraquinone dyes is considered the results are : FIG. 10. 41 43 Wave -1eiqths. -- Chloroform. - - - - - ._ - Glacial acetic acid. EthRr. - . - . - . -\ ' \ \ \ '. T (1) The absorption is displaced towards the red end of the spec-trum by solution in sulphuric acid and in potassium hydroxide as compared with absorption of the alcoholic solution. (2) The displacement is greater for potassium hydroxide solutio 982 MEEK THE ABSORPTION SPECTRA OF SOME than for sulphuric acid solution. The one exception is purpurin, which was shown t o be an exception in other respects (T. 1916, 109 561). (3) The resolution in sulphuric acid solution is generally FIG. 11. much Wave - lengt hs.- - Alizarin-cyanine in anisole. 9 ) )) pyridine. , ,) phenol. - - _ - - - -- . - . - . -greater than in potassium hydroxide solution and this is the case most frequently on the violet side of the group of absorption bands. (4) For the few neutral solvents experimented with Kundt’ POLYHYDROXYANTHRAQUINONE DYES ETC. 983 law is in a general way true but it is quite wrong when acid and basic solvents are included. T?he Chcrnge in t?Le Absorption S p e c t m Produced b y the TTnriation of tlir Nutnher nnd Posifioir of the rl7ixochroines. Previously (T. 1916 109 556) the gerieralisations formulated by Georgievics (Morintsh. 1911 32 329 et sep.) on ths influence of hydroxyl groups on the colour cf lakes were criticised and four FIG. 12.Wave-length of centre of same band i n various solvents. rules were formulated which seemed to be more in harmony with the facts. Pursuing this point further the absorption curves of (1) alizarin (1 2-dihydroxyanthraquinone) (2) quinizarine (1 4-dihydroxyanthraquinone) (3) purpurin (1 2 4-trihydroxyanthra-quinone) (4) anthragallol (I 2 3-trihydroxyanthraquinone) in sulphuric acid indicated by the full lines in Figs. 1 to 4 respectively have been resolved into symmetrical bands shown by the dotted lines in the figures. It has frequently been suggested by various experimenters that the absorption in the visible and i 984 MEEK THE ABSORPTION SPECTRA 03’ SOME the ultra-violet portions of the spectrum is due to electrons associated with masses of various magnitudes and calculations in the case of some substances showing selective reflection gives a mass of the order of the molecule.I f we take the elementary curves in Figs. 1 to 4 and find the ratio of the values of m / p e , where rn is the mass of the electron e the charge and p the number of electrons per molecule for each set of elementary curves we obtain the numbers in table VIII. TABLE VIII. Relative values of mfpe for elementary bands. Band No. 1. Band No. 2. Band No. 3. Substance. - Alizarin .................. 7 1 Quinizarin ............... 1 1 3 Purpurin ............... 2 1 Anthragallol ............ 4 2 1 -From Table V I I I we see that the value of m/pe for the alizarin bands increases with increase in tho wave-length of the maximum of absorption whilst the reverse is the case with quinizarin.To a less degree purpurin and anthragallol show the same effect as quinizarin and alizarin respectively. I n alizarin the hydroxyl groups are in the positions 1 2 whilst in quinizarin the groups are in the 1 :4-positions. Similarly purpurin is 1 2 4 - and anthragallol is 1 2 3-trihydroxyanthraquinone. Hence from the above and also from the curves in Figs. 1 to 4 it will be seen that the effect of the position of the auxochromes seems t o be as follows : the closer the hydroxyl groups are to each other in the benzene nucleus the broader and less intense become the bands towards the red side of the absorption group. A comparison of the curves given in the previous paper for these substances in other solvents, for example in potassium hydroxide bears out the same con-clusion.Also it seems to be true that the proximity of the auxo-chromes in the benzene nucleus determines the displacement towards the red but the mere displacement towards the red with closeness of the auxochromes becomes relatively unimportant when compared with the decrease in intensity of absorption and to the increase in the breadth of the bands on the red side of the absorp-tion group. So far as displacement toward the longer wave-length with proximity of auxochromes is concerned that could be ex-plained by an increase in the period of oscillation of the electron due to an increase in the capacity of the whole system produced by the closer proximity of the auxochromes. The broadening of the bands relative to the intensity would be due to the increas POLYHYDROXYANTHRAQUINONE DYES ETC.985 in the friction to which the absorbing vibrating electrons are sub-jected for if we take a simple absorption band produced by electrons moving according to the equation (12 d t then the term ti- represents the allowance made for friction and the greater the value of 7; the greater the breadth of the absorp-tion band relative t o its intensity that is the greater the friction the broader the absorption bands. The results then of bringing the auxochromes close together in the benzene nucleus are: (1) A displacement of the absorption bands towards longer wave-lengths and (2) A decrease of the intensity of the bands relative to their breadth. The latter result produces a greater change on the colour than the former.It is responsible for the brown colour of such dyes as antIragallo1 and rufigallol in certain solvents. The A BsorytioiL Spectrum of Aliznriiz-Cyn~iiite in Piperidine. When a solution of strength N/lO4 was prepared 1 cm. thick-ness gave the absorption curve (1) in Fig. 13 half an hour after preparation. Taking the wave-length where the absorption is a maximum as the centre of an absorption band then curve (1) in Fig. 13 gives the bands tabulated in table IX. TABLE IX. Band. - 4 . R . C . D . E . F . Q . Wave-length ...... 5990 5757 5544 5442 5295 5153 5064 Intensity ............ 0.48 0.526 0.64 0.613 0.50 0.434 0.354 tensity ......... 5 3 1 2 4 6 7 The absorption changes while the observations are being taken, so that time readings are necessary t o obtain the absorption curve a t a definite time after the preparation of the solution.Examina-tion of the solution immediately it has been prepared shows that the bands A B and E are absent or a t least very faint and that with time they begin to appear. When the solution is freshly prepared C is the most intense band and next in intensity comes D. The solution was allowed to remain in the dark for forty-seven hours and the absorption curve mas then (2) of Fig. 13. (The vessel remained sealed throughout the experiments from the Relative order of in 986 MEEK THE ABSORPTION SPECTRA O F SOME moment when the alizarin-cyanine was added to the piperidine, and therefore water vapour and carbon dioxide were excluded.) 47 49 M FIG.13. i 55 57 Wave-length. 61 63 (1) Alizarin-cyanine in piperidine 4 hour after preparation.. 9 9 9 , 47 hours ,) 1 7 9 71 7 7 ,, (2) ( 3) > t ? 9 9 1 95 f 7 9 9 7 9 ammonia. (4) ( 5 ) Y Y 9 3 The same bands are still present but E F and G are only shown by a change in the gradient of the curve. The intensity of al POLYHYDROXYANTHRAQUIONE DYES ETC. 987 the bands has increased and A and a have increased t o a greater degree than C and D with the result that B is now the band of maximum intensity. The wave-lengths corresponding with the maxima of A and B have increased. That need not be considered as due to any shift of the bands but merely as the natural dis-placement of the maxima caused by the change in the relative intensities of the d and B bands with respect t o the G and D bands.Curve (3) Fig. 13 gives the absorption of the same thick-ness of the same solution seventy-one hours after preparation. The intensity of absorption throughout has decreased. The bands A and E still remain distinguishable but C’ and D have become merged into one band. After ninety-five hours from preparation the same solution has only two bands remaining namely B and D with a slight suggestion of d. The intensity has decreased further and the fading continues. The wave-lengths of maxima of absorption are now 5902 and 5454 and comparing the absorp-tion curve (4) with the curve for alizarin-cyanine in concentrated ammonia solution ( 5 ) a strong resemblance is observed. Fading of the solution or what is the same thing general decrease in intensity of the absorption throughout must be ex-plained by a decrease per unit volume of the number of vibrating systems giving the various bands but the disappearance from the absorption curve of the individual bands .4 C’ 3 F and G can only be explained by a broadening of these bands.This on the ordinary mechanical theory would mean that the frictional element in the forced vibrations causing these bands was increased, and that therefore systems with periods differing from the true natural period by large amounts are made to resonate. It is not assumed that the individual bands A C‘ E F and G have dis-appeared entirely but they have broadened t o such a degree that the observed curve does not show them resolved as separate bands. The conclusion drawn previously (T. 1916 109 555) that “ t h e more electropositive the nature of the radicle attached to the conjugate chain the lopger will be the wave-length of the maxi-mum of the absorption band,” is supported by the comparison of the absorption curves of alizarin-cyanine in alcohol and in piperidine. I n this case the absorption curve of the solution in piperidine shows an intensification of the bands toward the longer wave-length and a diminution of the intensity of the bands towards the shorter wave-length. With the solution in potassium hydr-oxide and the dyed fabrics on chrome alum and tin mordants, the absorption curves were broad and did not show the separate bands as such. This would mean that the friction is much greater on these niordanted fabrics and also in the potassium hydroxid 988 RlITTER AND SEN ACTION OF PHENYLHYDRAZINE solution than in the alcoholic solution and the displacement of the centre of the broad resultant band would then be given by the increase of the intensity of the elementary bands towards the red end of the spectrum when the electropositive nature of the radicle is increased. DACCA COLLEGE, DACCA E. BENGAL, INDIA. [Received May 25tA 1917.

ISSN:0368-1645    

DOI:10.1039/CT9171100969

出版商:RSC    

年代:1917

数据来源: RSC

摘要:

988 RlITTER AND SEN ACTION OF PHENYLHYDRAZINE I XXXIV.-Action oj' Pheriylhydrazine on Opianic, Nitro-opiunic and Phthulonic Acids Some Derivatives of Hydrazo- and Azii-phthalide. By PRAFULLA CHANDRA MITTER and JNANENDRA NATH SEN. THE action of phenylhydrazine on opiaiiic and nitro-opianic acids was first studied by Liebermaim (Ber. 1886 19 763) who found that' in the case of opianic acid on0 molecule of the acid reacts with one molecule of phenylhydrazine with the elimination of two molecules of water and the formation of a compound insoluble in alkalis t o which he attributed a ring strubture. I n the case of nitreopianic acid an intermediate product soluble in alkalis which therefore was regarded as the ordinary phenyl-hydrazine derivative of nitro-opianic acid was isolated.This sub-stance could be purified by dissolving in cold acetone and pre-cipitation with water. On recrystallisation from glacial acetic acid however it' was converted into a compound insoluble in alkalis and containing one molecule of water less than the phenyl-hydrazine derivative and t o this coinpound too a ring structure was assigned. A behaviour similar to that of opianic acid on treatment with phenylhydrazine had been observed by Roser in the case of a number of o-keto-carboxylic acids (Ber. 1885 18 802). I n every case from one molecule of keto-acid and one molecule of phenyl-hydrazine with the hydrazine 11 y d r azine For the stances in two molecules of water instead of one were eliminated, formation of ring compounds. Intermediate phenyl-derivatives formed by the primary action of phenyl-on the aldehydo-group could not be obtained.preparation of these compounds Roser heated the sub-alcoholic solution with phenyl hydrazine and acetic acid ON OPIANIC NITRO-OPIRNIC AND PHTHALONIC ACIDS. 989 whilst Liebermann treated the substances in aqueous solution with phenylhydrazine hydrochloride and sodium acetate. In both cases the reaction Look place in the presence of acetic acid. It has been found that in ethereal solution and with the free base the reaction takes place in a novel manner with the loss of only one molecule of wafer. The products can in some cases be crystallised from dilute acetone. They vary in their degree of stability aiid in some cases remain unchanged for days especially during the cold season.On treatment with acetic acid the substances are instantaneously converted by loss of a further moleculk of water into ring com-pounds identical with those obtained by Liebermann and others. For the phenylhydrazine derivative (for example from opianic acid) we have the choice of two alternative formulz, /\CH:N*NHPh 5Hd /\CH(NH*NHPh)>o lie01 Ico -- \/ R I P 0 Meo\/Co2H JIeO (1. ) (11.) We are in favour of formula 11 because on subsequent oxida-tion with mercuric oxide in acetone solution the phenylhydrazine derivatives are converted into deep-coloured substances which give all the usual reactioiis of azo-compounds. The formation of an azo-compound by oxidation is a definite indication in favour of the hycirazo-structure.With the ordinary formula such a change cannot be explained without assuming a considerable amount of molecular rearrangement and redistribution of linkiugs. The azophthalides which have been prepared in this way repre-sent an altogether new class of azo-compounds. The mechanism of the reaction in this case and in the case of amines generally appears to be as follows. The elimination of water takes place in the first instance between the aldehydo-group on the one hand and the amino- or imino-group on the other. The hydrogen atom of the carboxyl group subsequently oscillates to the nitrogen forming a phthalide ring. In the case of a primary amine the change may be represented thus : 'J""s(NHR)>~. )--In the case of secondary amines two molecules of the ainine react with one molecule of the aldehyde aiid when the hydrogen atom of the carboxyl group oscillates to the nitrogen atom a molecul 990 MITTER AND SEN ACTION OF PHENYLHYDRAZINE of the amine is regenerated which is at once detached from the condensation product thus : I n the case of phenylhydrazine the action is exactly similar thus: \/\CH(NH *NHPb) I /co-->o./\/ The formation of stable azo-compounds by oxidation would thus be readily explained and they would have the structure repre-sented below : \/\CH(NH*NHPh)> ),)co--The oscillating hydrogen atom can of course reveri a t any moment to the original position which it apparently does in acid and alkaline media. This explains the solubility of the substance in alkalis as well as the formation of the phthalazone ring under the dehydrating influence of different acids.On oxidation t o the azo-compounds the hydrogen atom is removed with the result that the products become insoluble in alkalis unlike the hydrazo-compounds. Such oscillation of hydrogen of the carboxyl group to doubly or trebly linked atoms or radicles in the 0-position with respect to the carboxyl group is not without many parallels. E X P E R I M E N T A L . fnterctctioii of I'her~yliLynrtcsirte uw? Oyitrrric ,4 cid. Opianic acid is rather sparingly soluble in ether but 011 adding the acid to an ethereal solution of phenylhydrazine i t dissolves readily. The solution on keeping deposits minute crystals of the phenylhydrazine derivative. Five grams of phenylhydrazine hydrochloride were 'created with sodium hydroxide and to the ethereal solution of the liberated base 5 grams of opianic acid were gradually added with constant stirring the vessel being kept cool with ice-water.The acid dis-solved and on scratching the sides of the vessel minute crystals soon appeared. To ensure completion of the reaction the mixture was allowed to remain for about half an hour. The precipitate was washed repeatedly with ether and then dried in the air. The yield was 5.5 grams ON OPIANIC NITRO-OPIANIC AND PHTHALONIC ACIDS. 991 The substance crystallises from dilute acetone in pale piilk needles melting and decomposing a t 146O. It is soluble not only in dilute alkali carbonate but also in dilute sodium hydroxide and ammonia and less readily so in sodium hydrogen carbonate.I n the cold it does not dissolve in hydrochloric acid but on warming solution takes place. Concentra.ted nitric acid dissolves i t immedi-ately with the evolution of nitrous fumes and the production of a deep red colour. With concentrated sulphuric acid i t gives no colour. Acetic acid transforms i t into the ring compound: 0.1454 gave 0.3413 CO and 0.0786 H,O. 0’0996 , 7.9 C.C. N a t 2 1 . 5 O and 760 mm. N=9*19. The substance was dissolved in dilute standard alkali and the It was found 0-1889 required 6.4 C.C. N/lO-acid whilst this weight of a mono-C=64*02; H=6*01. Cl,Hl,O,N requires C = 64.00 ; H = 5.33 ; N =9.33 per cent. excess of alkali titrated with standard oxalic acid. to be monobasic. basic acid of the above formula requires 6.28 C.C.N/lO-acid. P h e ?i y la z om e co tz in. One gram of phenylhydrazorneconin (formula 11) was dissolved in 25 C.C. of pure acetone (free from methyl alcohol) and heated on the water-bath with 4 grams of red mercuric oxide the liquid being kept almost a t boiling point. The colour of the solution gradually changed to crimson-red. After remaining overnight the mixture was filtered and the filtrate allowed to evaporate in the air when a pasty mass was left which became hard on treatment with ether. The substance was dissolved in acetone and ether added to the solution. A pale yellow flocculent precipitate was formed which had a tendency t o become tarry and after removing this by filtration the filtrate was allowed t o evaporate in a vacuum over Bulphuric acid.A residue was left which after crystallisa-tion from dilute acetic acid was obtained as a yellow crystalline powder melting a t 1 6 4 O . I’henylazomeconilz gives all the usual reactions of an azo-com-pound. With concentrated sulphuric acid i t gives a violet colour. The colour of the substance itself is discharged by treatment with a solution of stannous chloride and hydrochloric acid. It dissoIves in glacial acetic acid with a red colour which intensifies on warm-ing. If to this solution zinc dust is added and the whole heated for a moment the colour changes t o pale yellow with the forma-tion of a precipitate. I n alcohol i t dissolves with a pink colour, which deepens on the addition of alkalis. It is readily soluble in acetone chloroform or benzene 992 MITTER AND SEN ACTION OF PHENYLHYDRAZINE 0.1034 gave 0.2438 CO and 0.0449 H,O.0*1003 , 8.4 C.C. N a t 2 5 O and 760 mm. N=9.59. C=64*34; H-4.82. C,,H,,O,N requires c = 64.43 ; H = 4.69 ; N = 9.39 per cent. Phenylop’azone. One gram of phenylhydrazomeconin was dissolved in hot glacial acetic acid the solution boiled for about five minutes and water added when the ring compound was precipitated in almost colour-less flakes. It was purified by redissolving it in dilute acetic acid and boiling with animal charcoal. On filtration and cooling, crystals separated which were perfectly transparent and melted sharply a t 175O. (Found C= 68.62 ; H = 5.26. C,,H,,0,N2 requires C = 68.08 ; H =4*96 per cent.) This substance is identical with the opianylphenylhydrazide described by Liebermann.It is insoluble in alkalis or alkali carbonates and does not develop any colour with concentrated sulphuric o r nitric acids. Interaction of Phenylhydrazirze atid Nitro-opianic A cid. To an ethereal solution of phenylhydrazine (from 1.5 grams of the hydrochloride) 1 gram of nitro-opianic acid was gradually added. I n a few minutes after solution was complete a red oil settled to the bottom which on stirring solidified to a crystalline mass which was collected and washed with ether. It crystallised from dilute acetone in red needles melting a t 184O (Found: N= 12.26. C;,Hl5O6N3 requires N = 12-17 per cent.) evidently identical with Liebermann’s (‘ nitro-opianic acid phenylhydrazine.” The substance is soluble in alkalis or alkali carbonates.With sulphuric acid i t gives but a pale green colour. Phenylhydrazonitromeconin (0 8 gram) was dissolved in 15 C.C. of pure acetone and 1.5 grams of red mercuric oxide were added. The liquid was kept gently boiling on a water-bath under reflux for about two hours after which it was left a t the ordinary temperature for twenty-four hours. The mixture was then filtered, the residue repeatedly extracted with boiling acetone and the acetone solution evaporated when a brick-red crystalline mass was obtained. This was treated with excess of sodium carbonate to remove any trace of the hydrazo-compound thoroughly washed with water and crystallised from dilute acetone from which i ON OPIANIC NITRO-OPIANIC AND PHTHALONIC ACIDS. 993 separated as an orange crystalline powder melting sharply a t 217'.The substance is sparingly soluble in acetone and insoluble in all other common solvents. With concentrated sulphuric acid i t gives a blue colour: 0.0959 gave 0.1976 CO and 0.0286 H,O. 0.1632 , 17 C.C. N a t 20° and 760.01 mm. N=12*14. C=56.19; H=3*32. C,,H,,06N requires C = 55-97 ; H'= 3-79 ; N = 12.26 per cent. With phthalonic acid and phenylhydrazine an intermediate hydrazo-compound was obtained which could be oxidised t o the corresponding azo-compound by means of mercuric oxide in acetone solution. It was also coaverted into the corresponding ring com-pound by dehydration with acetic acid. The hydrazo- and azo-compounds .have not however been obtained in a conclition sufficiently pure for analysis. Phenylpht halazoneca~-box~lic A cid, /\cop- YPh. (\/C(CO,H > N One gram of phenylhydrazophthalidecarboxylic acid was dis-solved in warm glacial acetic acid and hot water added t o the solu-tion. On cooling crystals of the ring compound were obtained in matted needles melting a t 208O. The substance is identical with the aiihydrophenylhydrazi~~e-o-carboxyphenylglyoxylic acid pre-pared by Henriques (Ber. 1888 21 1610). Further investigations are in progress. SIR T. N. PALIT LABORATORY, COLLEGE OF SCIENOE, UNIVERSITY OF CALCUTTA. (Receinetl June 18th 191 7.

ISSN:0368-1645    

DOI:10.1039/CT9171100988

出版商:RSC    

年代:1917

数据来源: RSC