Search

The influence of a C3 substituent on the direction of bromination of estra-1,3,5 (10)-trien-17-one is discussed: Estrone and its methyl ether give mainly derivatives bromine-substituted in ring A, while the bromination of estrone acetate leads to the production of 16-mono- and 16,16,dibromo-substituted estrones.

In the reduction of mestranol acetate with metals in liquid ammonia, as well as the reduction of ring A and the splitting out of the acetoxy group, the addition of hydrogen to C17 takes place and the main products are the 17-vinyl and 17-ethyl derivatives (III) and (VII), respectively. Under conditions favoring the saponification of the acetate, the reduction product is the 17-ethylidene derivative (VIII).

The bromination of estrone acetate (Ia) leads to a mixture of acetates of 16α-bromo-16β-bromo-, and 16,16-dibromoestrone (IIa, IIIa, and IVa) in a ratio of 63:28:9. On treatment with an aqueous methanolic solution of potash, depending on the conditions, a mixture of (IIa) and (IIIa) gives 3,16α-dihydroxyestra-1,3,5(10)-trien-17-one (V) or 3,17β-dihydroxyestra-1,3,5(10)-trien-16-one (VI). When 5 g of (Ia) was brominated with 2.8 g of Br2 in chloroform and the products were chromatographed on silica gel, 0.36 g of (IVa), C20H22Br2O3, mp 165–166°C (from ether) 0.37 g of (IIIa), mp 169–170.5°C, 4.6 g of a mixture of (IIa) and (IIIa), 30 mg of (Ia) and 0.2 g of a mixture of 16α- and 16β-bromoestrones was obtained. The action of potash on a mixture of (IIa) and (IIIa) in aqueous MeOH at 20°C led to the epimerization of the (IIa) into (IIIa) and then the conversion of the latter into (V) with mp 203.5–206°C; diacetate with mp 172–173°C (acetone-ethanol). Similarly, but with heating (98°C, 3 h), a mixture of (IIa) and (IIIa) was converted into (VI), with mp 234–236°C. Characteristics of the IR and PMR spectra of the compounds obtained are given.