WATSON AND SEN: DYES DERIVED FROM QUERCETIN. 389XLI11.-D!yes Derived from Quercetin.By EDWIN ROY WATSON and KUMUD BEHARI SEN.IN a previous paper by one of us (this vol., p. 338) there isdescribed the introduction of an amino-group into the quercetinmolecule, which was effected with the object of deepening thecolour of the dye. The arriino-group did not, however, p.roducemuch effect in this direction. The present paper contains anaccount of further work with the object of preparing quercetinderivatives which would dye deep shades. This object has now beensatisfactorily attained.The methods adopted with the object of deepening the colourmay be classified as follows:(1) The introduction of bathychrome groups.(2) The introduction of additional auxochrome groups.(3) The introduction of additional chromophores390 WATSON AND SEN : DYES DERIVED FHOX QUERCETIN.(4) Modification of the molecule so as t o satisfy the conditionsrequired by a theory proposed by one of us (P., 1913, 29, 348),namely, thah the molecule should be quinonoid in all possibletautomeric forms.(1) The bntroduction of Bnthychrome Groups.-As 6/-nitro-quercetinpentamethyl ether had already been prepared (Zoc.cit.),an attempt was made to demethylate it, and so obtain 6I-nitro-quercetin. Only partial demethylation has been satisfactorilyaccomplished with the production of 61-nitroquercetin dimethylether, which on acetylation gives the triacetate. The formersubstance dissolves in aqueous potassium hydroxide t o a reddish-brown solution, and consequently as a dye has no special interest.(2) The Introduction 0,’ Additionat Auxochrome Groups.-Nothing further in this direction has been accomplished.Nieren-stein and Wheldale (Ber., 1911, 44, 3487) have described thepreparation of 8-hydroxyquercetinY which, however, dyes practi-cally the same shades as quercetin. Quercetinsulphonic acid hasbeen prepared with the object of subsequently converting it intothiolquercetin, but this object has not been attained. Attemptsto replace the br0mic.e atoms in mono- and di-bromoquercetinpentamethyl ether by anilino-groups did not succeed.(3) The Ivitroduction of Additional Chromophores.-Naphthol-azoquercetin dimethyl ether has been obtained by the partialdemethylation of the corrwponding pentamethyl ether, previouslydescribed.It dyes maroon shades on alum-mordanted cotton.Triacetylpercetin, obtained by the action of anhydrous aluminiumchloride on quercetin penta-acetate, contains four chromnphoree(ketonic groups), but has no deeper colour than quercetin. Bysimilarly heating puercetin perhtachloroacetate with anhydrousaluminium chloride there is obtained a chlorine-free substance, ofwhich the acetyl derivative melts at 248-250°, and which isevidently a hydroxyfurano-derivative of quercetin. This has muchthe same colour as the original dye. From a similar treatment ofpuercetin tribenzoate no crystalline substance could be isolated,the amorphous product showing again no deeper colour.(4) It was thought that if the pyrone ketponic group could bereplaced by the group CR-OH, the resulting compound wouldbehave like the dyes of the triphenylcarbinol series, namely, losea molecule of water and become permanently quinmoid with nopossibility of tautomerising into a non-quinonoid form, and thatthis should result in a deepening of the colour.This anticipationhas been realised in several ways. 3 : 4 : 5 : 7-Tetrahyd~oxy-2-m-p-dihydroxyphemgl-1 : 4-benzopyran has been obtained by the reduc-tion of quercetin by sodium amalgam, preferably in alcoholiWATSON AND SEN: DYES DERIVED FROM QUERCETIN. 391hydrochloric acid solution. It had been already prepared byHlasiwetz and Pfaundler ( J . pr. Chem., 1864, 94, 85)) but theseinvestigators neither analysed it nor recognised its constitution.It dissolves in alcohol with a magenta colour, and in aqueouspotassium hydroxide t o a green solution, but is so readily oxidisedt o quercetin that it is useless as a dye.By the action of dimethyl-aniline on quercetin in the presence of phosphoryl chloride thereis obtained a substance which dyes slaty-blue shades, the analysisof which agrees with 3 : Ei-dihydroxy-7-keto-4-p-cEi~nethylamino-ph e ny l-2 -m- p-di h y drox y p h 4-b enzo pyran,0 OHExperiments have also been made to prepare the same substancethrough the methyl ether. The action of phosphorus pentachlorideon quercetin pentamethyl ether gives a white, crystalline substance,C,,H2,,0,C16, which must be regarded ils 4-chloro-4-hydroxy-3 : 5 : 7-trimethoxy-2Lm-p-~i~ethoxy~~~~e?~yZ-~ : 4-h enzopyi-an, but attemptst o replace the chlorine atom by the action of dimethylaniline andother reagents have been unsuccessful.With hydriodic acid(D 1.7) quercetin is produced. By the action of Grignard's reagent(magnesium ethyl iodide) on quercetin pentaethyl ether there isobtaified the crimson oxonium salt 3 : 5 : 7-triethoxy-2-m-p-diethozy-phenfyk-4-ethyl-l : 4-h enzopyran anhydroh.ydriodide (I), which on01 OEt 01 OHde-ethylatiori by hydriodic acid is converted into the crimson3 : 5 : 7-t?~h,~cFroxy-2-rn-p-cEihydroxy~henyI-4-etkyl-l: 4-benzopyram an-hydrohydriodide (11). The corresponding base, liberated by sodiumacetate, dissolves in alcohol with a magenta colour, in aqueouspotassium hydroxide to a, deep blue solution, and dyes wool violet(on alum and chrome) and crimson (on tin).By the preparationof this substance the object of the present investigation has beensatisfactorily attained. It indicates a general method, which maybe of very great value, for the preparation of dyes of deep colourby the action of metallo-organic compounds on the ethers ofhydroxy-ketonic dyes392 WATSON AND SEN : DYES DERIVED FROM QUERCE'I'IX.I n the course of this work the following compounds have alsobeen obtained :2-Iiydroxy-3 : 5 : 7-trimethoxy-l : 4-benzopyro.ne, by the action ofcliromic acid on 6'-nitroquercetin pentamethyl ether ; the oxoniumsidphate, chloride, and bromide of monobromoquercetin penta-methyl ether; and an oxonium compound of methyl sulphate andquercetin pentamethyl ether, C20H2007,( CH,),SO,, isolated insmall quantity during the preparation of quercetin pentamethylether.The latter compound seems of interest in connexion withthe question of the constitution of oxonium salts. It has the samebright yellow colour as the other oxonium salts of quercetin penta-methyl ether already described (Zoc. cit.), and therefore should beassigned a similar quinonoid structure. The possibilities wouldseem t o be:0,Rle0 OMe 0 OMeMe S0,Me\/0 OMebut the first two formulae would aesume complete splitting of themethyl sulphate molecule, and the attachment of the methyl andS0,Me groups at distant parts of the molecule-an assumptionwhich seems scarcely consistent with the ready regeneration ofmethyl sulphate on treatment of the oxonium compound withwater; whilst the last formula is similar to those assigned t o theoxonium salts of dimethyl-4-pyrone, which are colourless.EXPERIMENTAL,6/-.Xitropuerceti.n Dime th y l E t h e r , CI5H4O2( OH),(O*CH,),*N02.For the preparation of this substance nitroquercetin pentamethylether was quickly powdered with its own weight of anhydrousaluminium chloride, and heated for one hour a t 160° in a flaskfitted with a cork and delivery-tube, the latter dipping undermercury so that the mixture could not attract moisture from theair.The product ww added gradually to dilute hydrochloric acid,collected, washed, dried, and crystallised from glacial acetic acid. IWATSON AND SEN: DYES DERIVED FROM QUERCETIN.393was obtained in yellow, needle-shaped crystals, melting a t 240°,readily soluble in acetone, only very moderately so in alcohol orbenzene, and soluble in aqueous potassium hydroxide with areddish-brown colour. For the removal of a trace of alumina it wasconverted into i b acetyl derivative, which was subsequently hydro-lysed :0.1045 gave 0-2080 CO, and 0-0341 H20. C=54.28; H=3.61.Cl7IIl3O,N requires C = 54-40 ; H = 3-46 per cent.The triace ta t e, C15H402( OAC)~( 0 CH3),*N02, was prepared byboiling the above compound with acetic anhydride and a trace ofpyridine for half-an-hour, cooling the solution, and adding alcohol,when the acetyl derivative was gradually deposited in white, oralmost white, lozenge-shaped crystals, melting at 206O :0.1080 gave 0-2190 CO, and 0.0371 H20.C=55-30; H=3.81.C23€I,,012N requires C= 55.09 ; H = 3.79 per cent.Qwercetinsulphonic Acid, C,,H,O,*SO,H.One gram of finely-powdered quercetin was gradually added to4 C.C. of sulphuric acid, and the mixture heated on the water-bathfor one or two hours. The yuercetin dimolved almost completely,and the sulphonic acid was deposited in fine crystals. After themixture had remained for some time, the sulphonic acid wasseparated by an asbestos filter, dried on a porous tile, washed withglacial acetic acid (in which i t is insoluble), and recrystallisedfrom water. It was thus obtained in yellow, needle-shaped crystals,which redden on drying over soda-lime, and become browner onheating to 1 4 0 O .It is readily soluble in water :0.1158 *gave 0.1999 CO, and 0.0298 H20. C=47.07 ; H =2-84.0*2233-E ,, 0.1291 BaSO,. S-7.94.0.2721 t lost il.2282 at. 140O. H20 = 16.23.C,,H,,O,,S requires C = 47.13 ; H = 2-61 ; X=8*37 per cent.C,,H,,010S,4H,0 requires H20 = 15.85 per cent.The sodium salt, C,,H4O2(0H),(ONa)*SO3Na, wits obtained as abright yellow, amorphous precipitate on adding an alcoholicsolution of fused sodium acetate to the sulphonic acid in the samesolvent. On drying it became green:0.2520 * gave 0.0853 Na2S04.N a p h t h ola t o q uer c e tin, dime t h y 1 e the r,Na= 10.97.C",,H801,SN~ requires Na = 10.80 per cent.C,,H,O,(OH),( O*CH3)2*N2*C,&&*OH,was obtained by heating the corresponding pentamethyl ether withits own weight of anhydraus aluminium chloride at 200° for one* Dried a t 140". t Air-driecl.VOL.cv. D 394 WATSON AND SEN : DYRS IIER1VE:D FROM QWERCETIN.hour. The product was gradually added to dilute hydrochloricacid, and the mixture was afterwards boiled. I n order to removeall alumina, the substance, after collecting and drying, was dis-solved in cold sulphuric acid, and precipitated by pouring thesolution into water. It was purified by solution in acetic acid, butcould not be obtained crystalline. Several preparations, however,all melted sharply at 242O. The substance has dyeing properties,and gave a maroon shade on alum-mordanted wool. It dissolvm inalkali with a red colour, and in cold sulphuric acid to an indigo-blue solution :0.1028 gave 0.2435 GO, aiicl 0.0383 H%O.@=64*50; H=4*14.C,,H200,N, requires C= 64.80 ; H = 4.00 per cent.I'riacet~lty.irercet,irL, C,,H20,(0H),Ac,,Eight grams of quercetin penta-acetate were mixed with twicethe weight of anhydrous aluminium chloride, and heated for onehour a t 1 6 0 O . The product was carefully added to dilutehydrochloric acid, and the mixture boiled for five minutes. Theinsoluble substance was collected, washed, dried (5 grams wereobtained), and puri lied by acetylating, recrystallising the acetylderivative, and subsequently hydrolysing. The product thusobtained cons'sted of yellow, needle-shaped crystals, was verysimilar to quercetin in appearance, and melted at about 300O. Itdissolved in aqueous potassium hydroxide with a yellow colour, andwas only sparingly soluble in alcohol, It formed no oxoniumsulphate. With boiling alcoholic sodium acetate solution a sodiumsalt, C21H1,0,,Na, was produced, which separated on cooling as ayellow, gelatinous precipitate, subsequently changing to needle-shaped crystals :O * l l ' i O gave 0.2521 CO, and 0.0420 H20.C=58*70; H-3.98.C2,H16010 requires O= 58.90 ; H = 3.74 per cent.Trince tylpuerce tin Yenta-ace tat e, C,,H20,(0Ac),Ac,.The 5 grams of crude triacetylquercetin above mentioned wereacetylated by boiling with acetic anhydride and a few drops ofpyridine, and on adding alcohol to the solution the penta-acetatewas slowly deposited in minute crystals. After three weeks3-7 grams were obtained. It was purified by crystallisation froniglacial acetic acid, and obtained in pale yellow, needle-shapedcrystals, melting at 208-211° :0.1303 gave 0.2789 CO, and 0.0482 H,O.C=58-37; H=4*10.c31H26015 requires C = 58.30 ; H = 4-07 per centWATSON AND SEN: DYES DERIVED FROM QUERCETIN. 3950.4934, on hydrolysis, gave 0.3343 triacetylquercetin = 67.7 percent.C21Hl105(OAc), requires 67.1 per cent.Quercetin pentachloroacetate, C,,H50,(O~CO*CH,C1),, was ob-tained by heating a t 135-140° for fifteen minutea a mixture ofchloroacetic anhydride and quercetin in the presence of a trace ofpyridine. On adding alcohol to the mixture i t was deposited inwhite, needle-shaped crystals, melting a t 180° :0.2625 gave 0*2721 RgCl.C25H150&15 requires C1= 25.93 per cent.Previous attempts to prepare this substance by the action ofchloroacetyl chloride on quercetin were unsuccessful. I n the pre-paration described, it is very necessary not to let the temperaturerise too high.On heating with anhydrous aluminium chloride it is convertedinto a hydroxyfurano-derivative of quercetin, which has a yellowcolour, and dissolves in aqueous potassium hydroxide t o a brownish-yellow solution.This gives an acetyl derivative, crystallising inwhite needles from alcohol and acetic acid, which melts a t248-250°, and contains no chlorine.Quercetin tribenzoate, C,,H502(0H)2(0*CO-C,H5)3, was obtained(1) by the Schotten Baumann method, and (2) by heating quer-cetin with excess of benzoic anhydride at 190-200° for two hours.I n the latter case alcohol was added to the mixture after cooling,and the precipitated substance was recrystallised, first from itmixture of nitrobenzene and alcohol, and then from acetone. Thelat'ter solvent deposits it in almost white needles, melting a t 173O:0.1258 gave 0.3221 CO, and 0.0428 H,O.C=69*82; H=3-78.C3tiIT22010 requires C = 70.30 ; H = 3-58 per cent.The product obtained by heating this substance with anhydrousaluminium chloride (benzoylquercetin 1 ) was yellow, and dissolvedin aqueous potassium hydroxide to a brownish-yellow solution.Neither it nor its acetyl derivative hm been obtained crystalline.C1= 25.63.3 : 4 : 5 ; 7-I'ctrahydroxy-2-m-p-dihya?roxyphenyl-l; 4-benzopyran,One gram of quercetin was dissolved in 40 C.C. of warm alcoholand 2 C.C.of concentrated hydrochloric acid, and the theoreticalquantity of sodium amalgam added. The mixture was kept agitatedand warm, and the solution at once became deep magenta coloured.After a time similar quantities of hydrochloric acid and sodiumamalgam were again added. The solution now showed strongabsorption from the yellow right into the ultra-violet portion ofC15H1207.D D 396 WATSON AND SEN: DYES DERIVED FROM QUERCETIN.the spectrum. The substance was precipitated by pouring thesolution into water, and when collected and dried on a porous tilepossessed a curious, pale purplish-green colour. It qrystallised freelyfrom alcohol in needles, but owing to the readiness with which itwas re-oxidised to quercetin i t could not be satisfactorily recrystal-lised.It was first dried in a vacuum, and finally in the steam-oven :0.1012 gave 0.2200 CO, and 0.0385 H,O.C,,H,,O, requires C = 59-21 ; H = 3-94 per cent.The same substance can be obtained by reduction in cold aqueousalkaline solution, but excess of sodium amalgam must be avoidedand the solution must be kept cold. It dissolves in alcohol witha magenta colour, and in aqueous alkali to a deep green solution.I n either solvent it is readily oxidised to quercetin, and on boilingwith acetic anhydride and a trace of pyridine there is obtainedonly quercetin penta-acetate.C=59.28 ; H =4*22.3 : 5 -Dihydroxy-7-k e to-4-p-dim e t h ylamirzo p h e nyL2-m-p-dihydro xy-phenyl-l : 4-b eizzolzyrait, C23N,,06N.One gram of quercetin was added gradually to a mixture of12 C.C.o€ diinethylaniline and 3 C.C. of phosphoryl chloride, andthe mixture was heated t o 120° for one hour. It wi~s then pouredinto water, excess of sodium acetate was added, and the mixtureevaporated with water several times to remove excess of dimethyl-aniline. The dark blue, insoluble substance was collected, washed,and treated with hot dilute hydrochloric acid, in which itnearly all dissolved to a maroon-coloured solution. The filteredsolution was treated with excess of sodium acetat'e, the darkblue precipitate collected, very thoroughly washed, dried on aporous tile over soda-lime, and finally extracted with ether t oremove any traces of dimethylaniline. The product thus obtainedis of a dark blue colour, only sparingly soluble in alcohol, with aviolet colour, moderately so in glacial acetic acid, dissolving morereadily in the dilute acid to a deep blue solution, and in hydro-chloric acid (concentrated or dilute) with a deep maroon colour.It does not melt a t 300° It dyes wool either mordanted withalum, chrome, tin, or iron, or unmordanted, in slaty-blue shades.I n order t o make certain that the product was not a mixture con-taining a little methyl-violet, obtained by the oxidation of dimethyl-aniline, t o which its tinctorial propertries might be due, a blankexperiment was performed by heating a mixture of dimethylanilineand phosphoryl chloride only, which gave no methyl-violet.More-over, the colour reactions of the dye on the fibre are quite differentfrom those of methyl-violet, especially the reactions with aciWATSON AND SEN: DYES DERIVED FROM QUERCETIN. 397(cherry-coloured with hydrochloric acid, reddish-brown with sul-phuric acid, reddish-orange spot with nitric acid) :0.1301 gave 0.3238 CO, and 0.0607 H,O.C = 67-87 ; H = 5-18.0.3560 ,, 12 C.C. N, (moist) a t 28O and 758 mm. N=3*69.C23H,,0,N requires C’- 68.14 ; H =4.69 ; N = 3-46 per cent.4-Chloro-4- Ji ydiw xy-3 : 5 : ‘7-trim e t hoxy -2-m-p-di i n e t Ji oxy phenyl-1 : 4-&enzopyran, C,,132,0,C1.Two grams of quercetin pentamethyl ether were mixed withabout half t,he volume of phosphorus pentachloride, and heatedin a sealed tube a t 145O for three hours. The contents of the tubebecame crimt;on and partly liquid.They were mixed with ether,and poured into ice and water. The ether was allowed t o evaporate,and the insoluble matter was collected, dried, and extracted withbenzene. The portion extracted by benzene was crystallised fromalcohol, and obtained in white or cream-coloured needla(0.8 gram). This substance is only moderately soluble in alcohol,and melts a t 220--222O, and appears to give oxonium salts:0.1052 gave 0.2277 CO, and 0.0456 H,O.0.2906 ,, 0.1035 AgC1. C1=8*80.On boiling with hydriodic acid (D 1.7) it is converted intoquercetin. Attempk to replace the chlorine atom by the action ofdimethylaniline, aniline, alcoholic ammonia, tin, and hydrochloricacid, zinc dust, and acetic acid and potassium cyanide were notsuccessful.C = 59.03 ; H = 4.81.C2,H2,10,C1 requires C = 58.75 ; H = 5.14 ; Cl = 8.69 per cent.3 : 5 : 7 - T r i e t l ~ o x y - 2 - m - p - d ~ e ~ l ~ o x ~ ~ ~ h e r ~ .y l - 4 - ~ ~ ~ ~ y l - l : 4-benzomrunA nhydrohydriodide, C,,H,,O,I.1.5 Grams (I mol.) of quercetin pentamethyl ether were dissolvedin dry ether, and to this solution was added Grignard’s reagent,prepared by dissolving 0.24 gram (3 mols.) of magnesium in1.6 grams (a little more than 3 mols.) of ethyl iodide in the presenceof dry ether. A pale yellow precipitate was produced, and thereaction was completed by heating the mixture on a water-bathfor four hours. The product was poured into dilute hydrochloricacid (1 : 20), when the pale yellow substance became crimson, theether was evaporated, and the insoluble matter was collected,washed, and dried on a tile. It crystallised from alcohol in crimsonneedles, melting at 169O.The yield was 1.5 grams:0-1181 gave 0.2399 CO, and 0.0642 H,O.0.3050 ,, 0.1251 AgI. 1=22.16.C = 55-40; H = 6.04.C,,H,O,I requires C’=55.66; H=6.01; I=21.82 per cent398 WATSON AND SEN: DYES DERIVED FROM QUERCETIN.3 : 5 : 7-Trihydroxy-2-rn-p-dihydroxyphenyl-4-ethyl-1 : 4-benzopyranAnhydrohydriodide, C,,II,,061,H20.One gram of the above substance was boiled for two hours with20 C.C. of hydriodic acid (D 1.7) and 10 C.C. of acetic anhydride,and the mixture, after cooling, was poured into 60 C.C. of waterand decolorised by the addition of a small amount of sodiumhydrogen sulphite. The new substance was thus obtained incrimson, needle-shaped crystals, somewhat soluble in water.Onthe addition of a few drops of alkali either to the aqueous or thealcoholic solution a blue coloration is produced :0.1048 gave 0.1709 CO, and 0.0376 H,O. C -44.47 ; H = 3-98.0.1992 ,, 0.1008 AgI. I=27*34.C,,Hli0,I requires C = 44.34 ; H = 3-69 ; I = 27.60 per cent.The colour-base was obtained as a dark violet solid, with ametallic-green reflex, by adding sodium acetate to the aqueoussolutiori of the Eydriodide. It dissolves in alcohol with a magentacolour, and dyes wool violet (on alum and chrome), crimson (ontin), and magenta when unmordanted.2-Hydroxy-3 : 5 : 'I-tri?nethozy-l : 4-b enzopyrone,C,H20,(0*CH,),*OH.A solution of chromic acid (2 grams) in glacial acetic acid(10 c.c.) was gradually added to a well-cooled solution of nitro-quercetin pentamethyl ether (1 gram) in the same solvent '(5 c.c.),and the mixture was allowed t o remain overnight.On pouring intowater, a colourless substance was precipitated, which crystallisedin needles on boiling the mixture. It was recrystallised fromalcohol, and melted a t 155-156O:0.1135 gavc0.2402 CO, and 0.0481 H,O.0.2151 ,, 0.6134 A@. OMe=37*01.Mo n o b om o qu erc e t i n penta m e t h yl e t h e r sulp ha t e,C=57.70; H=4*70.C12H1206 requires (2-57-14; H=4.76; OMe=36*91 per cent,~20H,,0,Br>H2SO,,was prepared by adding a few drops of sulphuric acid to a solutionof monobromoquercetin pentamethyl ether in glacial acetic acid.It was obtained in bright yellow, needleshaped crystals, whichcould be dried in the steam-oven without decomposition. A weighedquantity was decomposed by boiling water, and the, acid liberatedwas determined by titration of the filtrate :0.5041 required lS.6 C.C. N/lO-H,SO,.The hydrochloride, C,,H,,O7Br,HC1, was similarly obtained inH,SO,= 18.07.C20H,90iBr,H2S0, requires H,SO, = 17-35 per centCONDENSATION OF KETONES WITH PHENOLS. PART I. 399bright yellow, needle-shaped crystals, and was dried in a vacuumdesiccator over sodaJime :0.2161 required 4.3 C.C. N / 10-HC1. HC1= 7-26.C2,H,90,Br,HCl requires RCl= 7-48 per cent.Quercetii~ I’entametlhyl .Ether Bimethyl Sulphate,C ‘ 2 - p .(,q 7 (CH,), s 0,.I n the preparation of quercetin pentamethyl ether alreadydescribed (Zoc. c i t . ) the mixture obtained by rubbing the drypotassium salt of quercetin trimethyl ether with methyl sulphatewas first washed with ether t o remove excess of methyl sulphate.On several occasions it wits noticed that the ethereal solutiondeposited bright yellow, needle-shaped crystals as it spontaneouslyevaporated. This substance appears to consist of an oxoniumcompound of the above composition, for on boiling with water thecolour disappears; an oil possessing the odour of methyl sulphateis produced, and, on cooling, the solution gradually depositsquercetin pentamethyl ether :0.2334 gave 0.1147 BaSO,. S=6*74.CWH,,O7,(CH3),SO, requires S = 6-42 per cent.CHEMICAL LABORATORY, DACCA COLLEGE,DACCA, E. BEXGAL, INDIA