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and the mixture was heated on the steam bath for 1 hr. After the reaction mixture was allowed to stand in the refrigerator overnight, the precipitated thiamine-S" bromide hydrobromide was filtered. Additional material was obtained by dilution of the mother liquor with anhydrous ether. The crude reaction product melted at 239-240' with decomposition.? The crude thiamineW was recrystallized by dissolving in 2 ml. of anhydrous methanol and diluting the solution with 20 ml. of anhydrous ether. The yield was 81 mg. (90%) of thiamine-Ss bromide hydrobromide with a m.p. 229-231' (with dec.). It was found that condensation of 25-75 mg. of thiazole with an equimolar amount of pyrimidine gave thiamine yield8 from 74-93 % of once-recrystallized material, the average yield being 87%. We observed that refluxing for more than 1 hr. did not improve the yield, and that the best yields were obtained when the condensation was allowed to take place in the minimum amount of ethanol necessary to dissolve the pyrimidine. A sample of thiamine bromide hydrobromide prepared from nonradioactive thiourea according to the above procedure was analyzed. Anal. Calcd. for C12HL8Br2NaOS: N, 13.4; Br, 37.50. Found: N, 13.04; Br, 37.50. When thiourea-Sa6 with a radioactivity content of 6 mc. per 100 mg. was used, the thiamine-S= bromide hydrobrornide obtained had a specific activity of about 1.4 mc. per 100 mg.
The Elbs persulfate oxidation of angelicin under the usual conditions2 met with failure. Similarly a parallel oxidation of 3',4-dimethyl-furo-7,8-(4',5')coumarin prepared according to Limayea also failed indicating the improbability of successfully effecting Elbs oxidation on coumarins with furan ring in the 7,8-position. A n attempt to introduce a hydroxyl group in 6-position by Elbs oxidation of I1 was unsuccessful. A stable coumarinic acid derivative4 was isolated, which regenerated the parent coumarin (11) on crystallization from acetic acid. The interaction of 5-methoxy-7-hydroxy4-methyl-8-formylcoumarins with ethyl bromacetate gave poor yield of ethyl 7-(5-methoxy4-methyl-8-formy1coumarinoxy)acetate (IV, R = C2Hb)which furnished the corresponding acid (IV, R = H) on hydrolysis with 5% methanolic potassium hydroxide. On refluxing this acid with fused sodium acetate in acetic anhydride, 4-methylisobergaptene (V) was obtained in poor yield. Some other dark, alkalisoluble material was obtained, which failed to give a definite product. This indicates an alternative method of synthesis of isobergaptene.
DEPARTMENT OF BIOCHEMISTRY FORDHAM UNIVERSITY NEWYORK58, N. Y.
( 7 ) With respect to the melting points of thiamine preparations, see Williams and Ronzio.*
v
IV Synthetic Experiments in the Furocoumarin Series R. M.NAIK A N D V. M. THAEOR Received March 1, 1957
In the course of our investigations on the synthesis of some naturally occurring furocoumarins, we required angelicin (I) as the starting material. In our effort to prepare it according to Spath and Pailer,' we observed the melting point of 7-(8-formy1coumarinoxy)aceticacid (11)t o be much higher (248-219") than what they stated (178-181 "). Moreover, this acid on heating with fused sodium acetate and acetic anhydride, gave a good yield of 2'-carboxyangelicin (111) along with angelicin (I). The authors do not appear t o have isolated the acid 111. This acid underwent smooth decarboxylation with quinoline and copper powder to furnish more oE angelicin (I).
I11 (1) E. Spath slid M. Pailer, Ber., 68B,941 (1935).
EXPERIMENTAL
All melting points are uncorrected. Ethyl 7-(8-jormy~coumarinosy)acetate. A mixture of 7-hydroxy-8-formyl-coumarin' (2 g. ), anhydrous potassium carbonate (6 9.) and ethyl bromoacetate (2.0 cc.) in dry acetone (100 c.c.), was gently refluxed on a water bath for 48 hr. The contents were filtered and the fitrate, on evaporation of acetone, yielded a white product along with the residual ethyl bromoacetate which was removed by closed steam distillation. The product crystallized from alcohol as shining flakes, m.p. 163'. Yield 1.6 g. Spath and Pager1 give m.p. 157' in a vacuum capillary. 7-(&Formy~coumarinoxy)acetic acid (11). The preceding ester (1 9.) was kept at room temperature with sodium hydroxide (8 cc., 5%) for 3 hr. when the ester slowly went into solution. The product which separated on acidification, crystallized from acetic acid as thin white needles, m.p. 248-249' (decomp.) Yield 0.7 g. The hydrolysis could also be brought about by 80% sulfuric acid at room temperature or boiling with 5% alco.holic potassium hydroxide. Since the previous authors' gave m.p. 178-181" (dec.) in a vacuum capillary, it was thought desirable to analyze the acid. Anal. Calcd. for C12H806: C, 58.1; H, 3.2. Found: C, 57.9; H, 3.3. (2) S. Sethna and co-workers, J . Znd. Chem. SOC., 27,369 (1950); 28, 366 (1951); 30, 610 (1953). (3) D. B. Limaye, (a) Ber., 65B, 375 (1932); (b) with D. D. Gangal, Rastiyanam, 1, 15 (1936); Chem. Abstr., 31, 2207 (1937). (4) C f . R. M. Naik and V. M. Thakor. J . Ora. Chem.,. 22,1&6( 1i57). (5) R. M. Naik and V. M. Thakor, J . Org. Chem., 22, 1630 (1957).
DECEMBER
1957
1697
NOTES
Angelicin (I) and 2'-carboxyangelicin (111). The mixture of Organic Sulfur Compounds. XXXIII. Action the above acid (11) (2 g.), freshly fused sodium acetate (5 of Some Free Radicals of Long Life on g.) and distilled acetic anhydride (40 cc.) was refluxed in oil bath a t 150-155" for 30 min. The reaction mixture was Thiophenol and p-Nitrothiophenol cooled and poured onto crushed ice whereupon the product separated. The contents were made alkaline with excess of ALEXANDER Scrriimmo A N I ) C A V I LA m sodium hydroxide, and then extracted with ether. Angelicin was isolated from the ether extract and crystallized from Received March 19, 1957 methanol as white needles, m.p. 138'. Yield 0.25 g. Spath and Pailer give m.p. 138-139.5". The alkaline layer was acidified and the product which Very little seems to be known about the reaction separated was crystallized from acetic acid as thin white between free radicals of long life and mercaptans, prisms m.p. > 315'. It melts sharply and leaves no residue. while the action of mercaptans on free radicals of Yield 0.9 g. A n a l . Calcd. for ClzHeOs: C, 62.6; H, 2.6. Found: C, 62.5; short life plays a great role in theoretical organic H, 2.8. chemistry in connection with the addition of merDecarboxylation of 8'-carboxyangelicin (111) to angelicin (I). The acid (111) (0.2 g.), copper powder (50 mg.) and dis- captans t o olefins under the influence of 1ight.l Experiments with triphenylmethyl and 9-phengltilled quinoline (5 cc.) were heated in an oil bath at 225' for half an hour. Copious evolution of carbon dioxide was Ruorenyl. Hexaphenylethane and 9,9'-diphenylobserved within 15 min. of heating. It was filtered and 9,9 '-bifluorenyl (I) dissolved separately in benzene washed with acetone, and dilute hydrochloric acid was were allowed to react with thiophenol in a stream added to remove quinoline. The ether extract of the conof COz. The action of triphenylmethyl on thiotents furnished angelicin (0.1 g.). Attempted Elbs persulfate oxidation of ungelicin (I). Po- phenol led to the formation of triphenylmethane tassium persulfate solution (2.7 g. in 60 cc. of water) was and triphenylphenylmercaptomethane, whereas the added dropwise t o a cooled (0') solution (obtained after experiments with 9-phenylfluorenyl and thiophenol warming) of angelicin (1.9 g.) in sodium hydroxide (20 cc.; IO%), and the reaction mixture was stirred. On working up yielded 9-phenylfluorene and 9-phenyl-9-phenylthe reaction mixture as blackish complex product mercaptofluorene. The formation of 9-phenylfluowas obtained which burned with conflagration and left be- rene was also observed when I, dissolved in boiling hind some residue. benzene, was allowed to react with thioacetic acid. Ethyl 7-(6-methoxy-~-methy~-8-fo~my~coumar~noxy)acetate It is possible that the reactions between triphen(IV, R = C2Hb).The mixture of 5-methoxy-7-hydroxy-4methyl-Sformylcoumarin (5 g.), anhydrous potassium car- ylmethyl and 9-phenylfluorenyl with thiophenol bonate (15 g.), ethyl bromacetate (5 cc.) and acetone (300 proceed according to A and B cc.) was refluxed on a steambath for 72 hr. The contents R3C. R'SH +RICH R'S. (A) were then filtered while hot and a good quantity of the unreacted substance (about 2.5 g.) was recovered as insoluble R'S. R3C. --+R3CSR' (B) potassium salt along with potassium carbonate. The filtrate, on evaporating acetone and working up as in the earlier experiment, furnished the ester which crystallized from or that hydrogen abstraction is essentially conacetic acid as thin wooly needles, m.p. 261". Yield 1.2 g. certed with formation of a carbon to sulfur bond. It does not give any color with alcoholic ferric chloride. R,C. CeHsSH R3C. +R3CH C6HaSCR3 Anal. Calcd. for Cl~Hl~O,: C, 60.0; H, 5.0. Found: C, 59.9; H, 5.1. Experiments with W,d'-diketo-S,3'-diphenyl-3,3' 7'-(6-Methoxy-~-methyl-8-fomylcouma~inoxy)acetic acid (IV, R = H). The preceding ester (IV, R = CzHb) ( 1 g . ) dicoumaranyl (11).I1 forms free radicals (IIIa +-+ was refluxed on a steambath for 30 min. with methanolic IIIb) in hot solutions. The dissociation2explains the potassium hydroxide (20 cc., 5%) when the product went fact that the cold solutions of I1 are colorless whereinto solution. A greenish product was obtained on acidifica- as the hot solutions are blue. tion. It was crystallized from excess of acetic acid, as amorphous needles, m.p. > 315'. Yield 0.5 g. CsHa I A n a l . Calcd. for Cl4H1207: C, 57.5; H, 4.1. Found: C, 57.8; H, 4.2. 4-Methylisobergaptene (V). The mixture of the acid (IV, R = H ) (1 g.) fused sodium acetate (2 g.) and acetic anhydride (15 cc.) was refluxed in oil bath a t 150-155" for 2 hr. Most of the acetic anhydride was removed by distillation I and then water and sodium hydroxide were added. The ether extract of this yielded 4methylisobergaptene which o,c=o i-H 2@: o,c-o' crystallized from alcohol in thin needles, m.p. 288-289". Yield 40 mg. IV IIIb Anal. Calcd. for ClsH&: C, 67.8; H, 4.3. Found: C, 67.6; H, 4.3.
+
+
+
+
+
+
Q-
Acknowledgment. The authors express their grateful thanks to Dr. R. C. Shah, for his keen interest in the progress of this work. DEPARTMENT OF ORGANIC CHEMISTRY INSTITUTE OF SCIENCE BOMBAY-1, INDIA
We have allowed I1 in hot chlorobenzene to react with thiophenol and p-nitrothiophenol. In both cases the sulfur compounds readily discharged the blue color of the solution. I n the case of thiophenol
(1) W. A. Noyes, Jr., and W. Bockolheide in A. Weissberger Technique of Organic Chemistry, Interscience, Inc., New York, 1949, Vol. 11, p. 138. (2) A. Lowenbein and H. Simonis, Ber., 57, 2040 (1924).
