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Vol. 72
molecular formula c24H&. Anal. Calcd. : c, 74.29; H, 9.34. Found: C, 74.53; H, 9.18. The additional carbon atom was shown to be in a methoxyl group by Zeisel determination (calcd. 7.99; found 8.59). When an ethanol solution of potassium hydroxide was used for the reaction a different product, the corresponding ethoxy compound, was obtained, m. p. 143-144.5') [.ID - 30.6' (chloroform). These results clearly prove that the reaction led to the formation of an ether rather than an alcohol. An examination of Marker's analytical data shows that there is equally good agreement for a methoxy derivative. The addition of alcohol to an a,P-unsaturated 20-ketosteroid is entirely analogous to the baseHICKRILL CHEMICAL RESEARCH FOUNDATION W. VON E. DOERING catalyzed addition of alcohols to methyl acrylate KATONAH, NEWYORK LAWRENCE H. KNOX or acrylonitrile to yield @-alkoxy propionic acid derivative^.^ The product formed from 3PRECEIVED APRIL6, 1950 acetoxy- Ab*l6-pregnadien-2O-one upon treatment with methanolic potassium hydroxide is therefore THE ACTION OF METHANOLIC POTASSIUM HY- 3P-hydroxy-l B-methoxy- A5-pregnen-20-one. The DROXIDE ON A A'B-20-KETOSTEROID: ISOLATION reaction is reversible, and an equilibrium mixture OF 3p-ACETOXY- 16-METHOXY-A'-PREGNEN-20- containing 69% of the 16-methoxy compound ONE spectrophotometrically is reached from either Sir : compound a t 23' in 3% methanolic potassium The reaction recently described by Marker' hydroxide in about two hours. for the introduction of a 17-hydroxyl group could (5) Koelsch, THISJOURNAL, 65, 437 (1913). have great significance in the synthesis of adrenal SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH DAVIDK. FUKUSHIMA cortical hormones. Since no evidence was offered T. F. GALLAGHER for the presence of a 17-hydroxyl group other than NEWYORK,N. Y. RECEIVED MARCH 21, 1950 failure to acetylate the newly introduced oxygen function, and since the reaction postulated was improbable, we have investigated the problem and A NEW ROUTE TO 11-KETOSTEROIDS have arrived a t a completely different conclusion. Sir: 30-Acetoxy- 16-pregnadien-20-one was reWhereas 3-hydroxyl groups usually resist atfluxed with a solution of potassium hydroxide in tack by N-bromosuccinimide in aqueous acetone,' methanol. As evidenced by the ultraviolet methyl 3a-hydroxy-ga,lla-oxidocholanate (I, absorption spectrum, E::*, = 121 a t 2390 A., ap- from the 9,11-ethylene,2*3m. p. 135.4-136.4', proximately half the product no longer contained [ a I z 5 D +22' Chf.4 Anal. C25H4004: c, 74.21, the alp-unsaturated carbonyl group of the initial H, 9.97. Found: C, 74.51; H, 10.09) is oxidized compound. Acetylation followed by chromatog- to the 3-ketone (11, m. p. 129-130°, [ C U ] 4-4' ~~D raphy resulted in the separation of 30-acetoxy- DL4 Anal. C]25H3804: C, 74.52; H, 9.52. A5016-pregnadien-20-oneand a compound, m. p. Found: C, 74.34; H, 9.38. Semicarbazone, m. p. 158.5-159.5'; [ a I z 5-28.5' ~ (chloroform), which 209-210'; Wolff-Kishner reduction to 9 a ) l l a showed no absorption in the ultraviolet above oxidocholanic acid, m. p. 158-159', [ a ] 2 $17' 2~ 2250 A. The possibility that the compound was DL5 Anal. C&H3803: C, 76.96; H, 10.23. a 3P-acetoxy-17-hydroxy- A5-pregnen-20-onewas Found: C, 76.93; H, 10.42). Chromic acid oxireadily eliminated by comparison of the physical dation of I or I1 gives the hemiketal 111, rn. . constants with the known epimers ( 1 7 d m. p. 119-120' (variable), [ a I z 3+102' ~ Chf., X,"', 234-235'; [ a ] D -41.8' [dioxane]; 17@-3m. p. 2.85, 5.78, 5 . 8 5 ~ . Anal. Cj25H3805: C, 71.66; 187-188'; [a]D -61.3' (chloroform)). A D9.16. Found: C, 71.89; H, 9.20. Acetate homosteroid was similarly discarded as a possible H, (BFa-AczO), p. 148.6-149.8', [aIz4D +100.3' interpretation. The most important evidence Chf. Anal. m. C27H4006: 70.38; H, 8.77. against these structures was provided by infrared Found: C, 70.27; H, C,8.76. ether spectrometry4 which revealed that no free hy- (CH30H-HBr), m. p. 124.8-125.5', Methyl [a]'*D f92.3' droxyl group was present in the product. (1) Fieser and Rajagopalan, THIS JOURNAL, 11, 3935, 3938 The elementary analysis conformed to the (1949). (2) Seebeck and Reichstein, Hclv. Chim. Acto, 26, 536 (1943). (1) Marker, THISJOURNAL, 71, 4149 (1949). mp (log E ) a t 235 (4.26)) 327 (3.78), 368 (3.59) and 392 (3.11) and minima a t 273 (3.25)) 363 (3.57) and 387 (3.30). I1 absorbs four molar equivalents of hydrogen in ethanol with platinum oxide giving an oil oxidized with permanganate to pimelic acid, m. p. 99-102' (m. p. 100- 102' in admixture with authentic material, m. p. 101102'). These facts are consistent with the assignment of tropolone (IIa) as the structural hypothesis for I1 but do not completely exclude IIb. This investigation was supported in part by a research grant from the National Institutes of Health, Public Health Service, and in part by a research grant from the American Cancer Society.
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(2) Hegner and Reichstein, Hrlu. Chim. A c f a , 42, 828 (1941). (3) Shoppee and Prius, ibid., 26, 201 (1943). (4) We wish to express our appreciation to Dr. Konrad Dobriner of this Institute, who determined and interpreted the infrared spectra for us.
(3) Mattox, Turner, Engel, McKenzie, McGuckin and Kendall, J . B i d . Chcm., 162, 569 (1946). (4) Chf. chloroform; Di. dioxane; An. acetone. (5) Alther and Reichstein, Rclu. Chim. Acta, 16, 492 (1943), give [U]D +18.8' An. for the methyl ester.
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