954 NAYLOR AND DYER: OROXYLIN. By WILLIAM ARTHUR HARRISON NAYLOR and CHARLES STANLEY DYER. THE bark of Oroxyluin indicunz mas examined by Naylor and Chaplin in 1890 (Year Book of Pl~ccrnzc~cy), and among the substances then separated was a yellow, crystalline compound, to which they gave, provisionally, the name of oroxylin. Its conduct towards certain reagents was noted, and particularly its behaviour with sodium and potassium hydroxides, which resulted in the production of an intense red colour, quickly passing into a dark green. For the opportunity to study more intimately this interesting con- stituent, we are indebted to Mr. David Hooper., of Calcutta, who kindly collected and shipped to one of us a considerable quantity of the bnrk. Isolation of Oroxylin. The bark, reduced to No.20 powder, was exhausted with 90 per cent. alcohol by percolation, the percolate concentrated by distilling off most of the spirit, and the resulting liquid poured into eight times its volume of water, when the oroxylin was precipitated together with wax, fat, and resinous substances. The bulky precipitate was collected, washed with water, and dried in a water-oven. When quite dry, it was treated with chloroform until most of the wax, fat, and resinous substance had been withdrawn. It was then exhausted with ether, the ethereal liquid distilled, and the residue washed with light petrol- eum to remove the last traces of fat. This purified residue was dis- solved in alcohol, in which it readily dissolved. The solution, after filtration, was diluted with hot water until a faint cloudiness appeared, and set aside to crystallise.It crystal- lises in sharply defined, golden-yellow needles about 1/6 inch in length, is readily soluble in alcohol or hot glacial acetic acid, less so in ether, sparingly so in chloroform, and practically insoluble in water. Oroxylin begins to melt at 225O. When burnt with cupric oxide in a current of oxygen, the following numbers were obtained : The yield of pure oroxylin is about 2 parts per 1000. C19H1400 (1). (2). (3) Werner. requires C . , . .. , , , , 67-42 67.43 67.49 67.45 per cent. H ...... 4.51 4.6 4.38 4.14 ,) For the purpose of comparison, we give the percentage numbers obtained by Werner (Pharm. Journ., 1898, [iv], 7, 390)) and it will be noted that ours are in close agreement with his.From these figures,NAYLOR AND DYER : OROXYLIN. 955 and others to be presently mentioned, me believe the formula for oroxylin to be CI,Hl,O,. AS oroxylin rapidly reduces silver compounds, the formation of a definite silver salt was not possible. The addition of lead acetate dissolved in weak alcohol to an alcoholic solution of oroxylin gives a light red, bulky precipitate of indefinite composition. Devivntives of Oroxglin. Friacetyloroxylin, C,,H, O,H,O,),.-In our first attempt to acetylate oroxylin we acted on it direct with acetyl chloride, but the method proved unsatisfactory, the product being resinous and the yield of crystallisable substance disproportionately small. Eventually, the acetic anhydride and dry sodium acetate were adopted.The action which in the early stages took place rapidly, on the application of the heat of a water-bath, mas complete in half an hour. To isolate the derivative, the mixture, after the addition of a little ether, was poured into water. The ether was blown off, when the in- soluble product gradually solidified. It was collected, washed with water, then cautiously with ether which removed resinous matter, and finally was crgstallised from alcohol. This colourless product con- sisted of minute, white, acicular crystals melting a t 150-152' with partial decomposition into oroxylin. When hydrolysed by warming for half an hour with slightly diluted sulphuric or hydrochloric acid and then pouring the liquid into water the regenerated oroxylin is precipitated, and may be collected, mashed with water, dried at 110", and weighed.In this manner, the following results were obtained froin the acetyl derivative by hydrolysis : (i) 0.2'79 gave 0.205 oroxylin, equivalent to 73.47 per cent. On cooling, the whole solidified, forming a crystalliiie mass. (ii) 0.302 ), 0.220 ,, ?, 72.84 y , (iii) 0.430 ,, 0.314 ,, 7, 73.02 ,, Cl,Hl,0,(C2H,0)3 contains oroxylin = 72*S4 per cent. Dibrornovoxglin, C,,H,,O,Br,.-One gram of oroxylin was dissolved by heating with 20 C.C. of glacial acetic acid, and to the solution was added 1 C.C. of bromine. The mixture was allowed to evaporate on a water-bath until i t commenced to crystallise, when it was set aside and the mother liquor poured off from the crystalline magma. The product, after three recrystallisations from acetic acid, was obtained in pale yellow needles which began to melt at 1'73' and dissolved readily in alcohol or ether.0.308 gave 0.233 AgBr. Br =32*19. 0.428 ,) 0.320 AgBr. Er = 31.81. C,9H,20,Br, requires Br = 32.23 per cent.056 NAYLOR AND DYER: OROXYLIN. Deconaposition Products. Oroxylin was boiled for half an hour with a 50 per cent. solution of caustic potash, When cold, it was diluted with water, neutralised with hydrochloric acid, and agitated with ether. The ethereal lager yielded a small quantity of a neutral substance, which, after puri- fication, answered the test for phloroglucinol with pinewood and hydrochloric acid. The neutralised liquid was then acidified and again shaken with ether, The ethereal layer left, after evaporation, a much coloured residue.The crude product was extracted with light petroleum, which by slow evaporation gave a crop of fine, colourless needles having an aromatic odour. This crystalline sub- stance sublimed unchanged, melting a t 1209 An aqueous solutioa, when neutralised by caustic soda, gave a reddish-brown colour with neutral ferric chloride. Its melting point, solubilities, and behaviour towards reagents afford conclusive evidence that it is benzoic acid. A second quantity of oroxylin was similarly treated with a 20 per cent. solution of caustic potash with a similar result, except that in addition to benzoic acid a small quantity of phthalic acid was detected. A third quantity was digested for half an hour with fused potash maintained a t a temperature of about 180'.Again the chief pro- duct proved to be benzoic acid. When oroxylin was allowed to stand in a 5 per cent. solution of potassium hydroxide at the ordinary temperature, a considerable liberation of benzaldehyde occurred. Potassium permanganate is instantly decolorised by oroxylin, phthalic acid being one of the products of the reaction, as recognised through the fluorescence resulting from the interaction with resorcinol. The following negative results indicate the absence of a methoxyl or ketonic group in oroxylin, and also prove that it is not a weak acid. 1. The application of Zeisel's method for the estimation of meth- oxyl gave negative results, 2. When treated with a mixture in suitable proportions of pot- assium iodide and iodate, there was not the faintest liberation of iodine. 3. Several attempts were made to induce oroxylin to interact with phenylhydrazine, but without success, neither phenylhydrazine in the. presence of acetic acid, nor its hydrochloride, with or without acid, sufficed to convert it into a hydrazone. Summarising the results at present obtained, it appears that oroxylin forms a dibromo-derivative, that i t contains an easily de- tached benzene nucleus, that three hydroxyl groups are present, and that its composition may be represented by the formula C,,H,,O,.