The Journal of Organic Chemistry 1957 Volume.22 No.6
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THE JOURNAL OF Organic Chemistry © Copy righi 1957 Volume 22, Number 6 by the American Chemical Society June 12, 1957 [CONTRIBUTION FROM THE CHEMISTRY DEPARTMENT, T h e UNIVERSITY, ABERDEEN] Flavothebaone. VI.1 Oxidation of Nitrogen-Free Products K. W. BENTLEY a n d J. P. RINGE Received December 17, 1956 The oxidation of flavothebaone trimethyl ether hexahydrodesazamethine, dihydrodesaza-\i'-methine, dihydrodesazaneo- methine, and of dihydro-Compound-E with chromic acid, results in the production of aromatic ketones, by oxidation of the methylene group adjacent to the veratrole nucleus. In addition the dihydrodesaza-^-methine and dihydro-Compound-E have been oxidized by peroxytrifluoroacetic acid, with attack of the ethylenic linkage. All the reaction products have been satisfactorily formulated on the basis of the structures previously assigned to these nitrogen-free products in the flavothe baone series. In a search for methods of further degradation of of piperonylidenedihydroflavothebaone trimethyl flavothebaone derivatives the oxidation of several ether (V)3 (Xmax 2,600; 2,900; 3,500 A, emax 12,600; nitrogen-free products has been investigated. It was 10,000; 14,100), which contains an analogous hoped thus to open the ketonic ring of the hexahy conjugated system. Further oxidation of the dike drodesazamethine (I) and obtain compounds re tone (IV, R = CH3CO) could not be effected. lated to the i/'-methine series. Oxidation of the ke Oxidation of ketones to esters using peroxytri tone (I) with chromic acid afforded, however, only fluoroacetic acid has been successfully accom 10-oxoflavothebaone trimethyl ether hexahydrodes plished by Sager and Duckworth4 5 and by Emmons azamethine (II), which gives a dioxime, and shows and Lucas,6 the latter two workers showing that in the infrared absorption bands characteristic of a the oxidation of methyl alkyl ketones the acetate saturated carbonyl group (1714 cm.-1) and an aro is invariably formed. Accordingly it was hoped that matic carbonyl group (1665 cm.-1). The same po oxidizing the dihydrodesaza-^-methine (III, R = sition is attacked by chromic acid in other com CH3CO) with this reagent might afford a method of pounds of the morphine group, e.g., the conversion removing the C H 3CO group with access to the of morphine into 10-hydroxymorphine.2 Attempts neomethine series (vide infra). Oxidation of the to oxidize the diketone (II) further failed. The oxi dihydrodesaza-i/'-methine, C25H28O5, in this way, dation of flavothebaone trimethyl ether dihydro-des- however, afforded only a very small amount of aza-^-methine (III, R = CH3CO) with chromic acid crystalline material, of composition C25H28O7. The likewise resulted only in converting the methylene ultraviolet spectrum of this product (Xmai 3,050 A, group to carbonyl, the product, oxoflavothebaone fmaj 7,770) indicates that the styrenoid double trimethyl ether dihydrodesaza-^-methine, being bond is no longer present, and the infrared spec given the structure of ll-acetyl-12-ethyl-l ,2,7,10- trum (bands at 1733 and 1690 cm.-1) indicates tetramethoxy - 5 - oxo - 5,12 - dihydrochrysofluorene the presence in the molecule of an ester group and (IV, R = CH3CO). This compound, which readily a carbonyl group, and the structure VI is ac gives a dioxime, contains one saturated and one cordingly suggested for the compound. Insufficient highly conjugated unsaturated carbonyl group material was obtained for further investigation. (infrared bands at 1704 and 1640 cm-1) and has an ultraviolet spectrum (Xmax 2,600; 2,950, 3,500 A, (3) K. W. Bentley, J. Dominguez, and J. P. Ringe, J. Org. emai 11,200; 15,900; 15,900) very similar to that Chem., 22, 418 (1957). (4) W. F. Sager and A. Duckworth, J. Am. Chem. Soc., (1) Part V, J. Org. Chem., 22, 424 (1957). 77, 188 (1955). (2) H. Rapoport and S. Masamune, ./. Am. Chem. Soc., (5) W. D. Emmons and G. B. Lucas, J. Am. Chem. Soc., 77, 6359 (1955). 77, 2287 (1955). 599 600 BENTLEY AND RINGE VOL. 22 Oxidation of flavothebaone trimethyl ether this substance, C25H28O6, with either peroxytrifluo- dihydrodesazaneomethine (III, R = OH', with roacetic acid, or with chromic acid, affords dihydro- chromic acid followed the same course as the ox Compound-Ei, C25H2806, which no longer shows idation of the dihydrodesaza-i/'-methine (III, R = stilbenoid absorption (Amax 2,900 A, emax 5,020), and CHgCO), the product, oxoflavothebaone trimethyl contains a saturated carbonyl group (infrared band ether dihydrodesazaneomethine, being given the at 1708 cm.-1) in place of the unsaturated carbonyl structure of 12-ethyl-ll-hydroxy-l,2,7,10-tetrame- group of the starting material; this confirms the thoxy-5-oxo-5,12-dihydrochrysofluorene (IV, R = view that the stilbenoid and a,/3-unsaturated OH). The ultraviolet spectrum of this product ketone double bonds of Compound-E and dihydro- (Amax 2,550; 2,900; 3,500 A, emax 15,100; 13,800, Compound-E are one and the same. In addition the 11,300) is very similar to that of the diketone marked change in optical rotation is going from (IV, R = CH3CO), and as the infrared spec dihydro-Compound-E ([a]D —68°) to dihydro- trum shows that it contains only one carbonyl Compound-Ei ([«] d + 248°) suggests the estab group (highly conjugated, band at 1640 cm.-1) lishment of new centers of dissymmetry in the and one hydroxyl group (band at 3585 cm.-1), it latter, and this compound is accordingly formu is clear that the sterically hindered —GH(OH)—- lated as (VIII). In the steroid field a,/3-unsaturated group of the neomethine derivative resists oxida ketones are known to afford epoxides by chromic tion. Unlike other neomethine derivatives this acid oxidation as well as by oxidation with per- substance resists dehydration on heating with acids,7'8 and in this field epoxides between fully formic acid, the product of the reaction being the substituted carbon atoms are much more stable formate ester, and doubtless this may be attrib than other sorts of epoxides. For example Staveley uted to the fact that the driving force behind the and Bollenback9 found, in the course of studies on other dehydrations in the neomethine series, the a-spinasterol, that the epoxide (IX) is stable to establishment of a new aromatic system, is absent boiling acetic acid, although it is dehydrated to in this case. (X) by heating with hydrochloric acid and acetic The allocation of structures of two compounds acid. The epoxide (VIII), however, was found in the flavothebaone series, namely Compound-E stable to acid and base-catalysed dehydration. (VII, R = CH=CH2) and dihydro-Compound-E Further, epoxides such as (IX) do not react with (VII, R = Et),6 rests on rather scanty evidence, the normal ketonic reagents due to steric hindrance and these structures have been further probed by the oxidation of dihydro-Compound-E. Oxidation of (7) O. Rosenheim and H. King, Nature, 139, 1015 (1937). (8) V. Petrow, J. Chem. Soc., 998 (1939). (6) K. W. Bentley, J. Dominguez, and J. P. Ringe, J. Org. (9) H. E. Staveley and G. N. Bollenback, J. Am. Chem. Chern., 22,409(1957). Soc., 65, 1600(1943). j u n e 1957 FLAVOTHEBAONE. VI 601 of the carbonyl group by the oxide ring,7’8 and in the final addition of peracid. An equal volume of chloroform agreement with the formulation (VIII), dihydro- was then added to the reaction mixture and the solution Compound-Ei fails to give an oxime or a dinitro- washed successively with water, 2N sodium carbonate solu tion, and aqueous sodium chloride. The dried solution phenylhydrazone. was then evaporated to dryness. The residual dark tar was Further oxidation of dihydro-Compound-Ei with dissolved in benzene and the solution chromatographed on chromic acid yields the diketone dihydro-Com- alumina; a bright orange band was eluted with benzene. pound-E2, C25H26O7, (XI) which contains one satu Evaporation of the eluate and*ecrystallization of the residue from methanol afforded 0.08 . of a compound believed to rated and one aromatic carbonyl group (infrared be ll-acetoxy-12-ethyl-l ,2,7, -tetramethoxy-6-oxo-5,6,12,13- bands at 1702 and 1675 cm.-1) and forms a mono- tetrahydrochrysofluorene (VI) 3 pale brown prisms, m.p. 2,4-dinitrophenylhydrazone. The satisfactory ac 232°, M 2d° -231° (CHCh, c. 0.28). commodation of these facts on the basis of the Anal. Calcd. for C25H2a07: C, 68.1; H, 6.4. Found: C, structure (VII, R = Et) for dihydro-Compound-E 67.8; H, 6.3. may be regarded as strong support for this formu Oxidation of flavothebaone trimethyl ether dihydrodesazaneo lation, and hence for the structure (VII, R = methine. A solution of chromium trioxide (0.9 g.) in 90% acetic acid (8 ml.) was slowly added to a cooled solution of CH=CH2) for Compound-E. flavothebaone trimethyl ether dihydrodesazaneomethine (2.3 g.) in acetic acid (100 ml.). After 10 min. the mixture was heated at 60° for 5 min., when a deep green solution EXPERIMENTAL was obtained. Water was then added and the product collected, washed with sodium carbonate and water, and Oxidation of flavothebaone trimethyl ether hexahydrodesaza- recrjrstallized from methanol, when oxoflavothebaone tri methine. A solution of chromium trioxide (2 g.) in 90% acetic methyl ether dihydrodesazaneomethine (IV, R = OH) was acid ( 8 ml.) was slowly added to a cooled solution of flavo obtained as pale yellow prisms, m.p. 193-194°, [a]2D3 +219° thebaone trimethyl ether hexahydrodesazamethine (5 g.) in (C H C I3 c. 0.76). acetic acid (40 ml.). A brown precipitate rapidly formed Anal. Calcd. for C23H2406: C, 69.7; H, 6.1. Found: C, and the mixture was heated for 2 0 min. on the steam bath, when a deep green solution was obtained.