Steroids. XXVII. Aromatization of 3-oxo steroids of the normal- and allo-series to 1-methylphenols

Abstract

cf. C.A. 46, 10185d. The aromatization of 2,4-dibromo-Δ1,4,6-triene 3-ketones of cholestanone, coprostanone, and of some 3-oxo-cholanic acid derivs. is described. Warming 5 g. Me 2,4-dibromo-3-oxo-12α-acetoxy-Δ1,4,6-cholatrienate in 75 cc. Ac2O with 5 cc. concd. H2SO4 in 50 cc. Ac2O 2.5 hrs. at 50-60°, keeping the mixt. 3 hrs. at 20°, and dropping it into 1 l. H2O give 3.95 g. Me 2,4-dibromo-3,12α-diacetoxy-1-methyl-19-nor-Δ1,3,5,6-cholatetraenate (I), m. 218-19°, [α]20D -45° (CHCl3), λmax. 229, 280, mμ, ε 27,600, 20,300 (MeOH). Refluxing 0.28 g. I in 10 cc. CHCl3, 50 cc. EtOH, and 6 cc. concd. HCl 2 hrs. gives 0.19 g. Et 2,4-dibromo-3-hydroxy-12α- acetoxy-1-methyl-19-nor-Δ1,3,5,6-cholatetraenate (II), needles, m. 201-1.5°, λmax. 229, 280 mμ, ε 23,400, 14,200 (MeOH). Refluxing 0.12 g. II in 50 cc. EtOH with 0.15 g. Pd black and 15 drops N2H4.H2O 1 hr., dilg. the filtered soln. with H2O, and extg. with ether give 0.065 g. Et 3-hydroxy-12α- acetoxy-1-methyl-19-nor-Δ1,3,5-cholatrienate, needles, m. 164°, λmax. 285 mμ, ε 2,500 (MeOH). Shaking 10 g. 2,4-dibromo- Δ1,4,6-cholestatrienone (III) in 200 cc. Ac2O with 75 cc. concd. H2SO4 in 100 cc. Ac2O 48 hrs. and filtering the soln. give 7.2 g. unchanged III. The filtrate is poured into H2O, the mixt. extd. with ether, and the residue of the ether ext. chromatographically purified, giving 1.6 g. 2,4-dibromo-3-acetoxy-1-methyl-19-nor-Δ1,3,5,6-cholestatetraene, needles, m. 163-4°, λmax. 298 mμ (MeOH), which (1.26 g.) is refluxed 2 hrs. in 20 cc. EtOH and 6 cc. concd. HCl and gives 100-200 mg. 2,4-dibromo-3-hydroxy-1-methyl-19-nor-Δ1,3,5,6-cholestatetraene (IV). Dilg. the mother liquor with H2O, extg. with ether, extg. the ether soln. with 5% NaOH and the acidified alk. soln. again with ether give another 300 mg. IV, prisms, m. 93-4°, [α]23D -56° (CHCl3), λmax. 232, 275, 315 mμ, ε 24,500, 11,700, 2,700 (MeOH). Adding slowly 25 drops N2H4.H2O to 0.2 g. IV in 30 cc. EtOH, 10 cc. 10% alc. NaOH, and 1 g. 20% Pd-CaCO3 and heating the mixt. 2 hrs. on a water bath give 0.12 g. 3-hydroxy-1-methyl-19-nor-Δ1,3,5-cholestatriene as an oil, λmax. 282 mμ, ε 1700. The soly. of I-IV and of other steroid phenols in 5% aq. KOH is discussed. [on SciFinder(R)]