Novel and regiospecific synthesis of 2-amino estrogens via Zincke nitration

An efficient synthesis of 2-aminoestrone (14), 2 aminoestradiol (15), 2-amino-16 alpha-hydroxyestrone (16) and 2-aminoestriol (17) is described. 2,4-Dibromo estrogens 1 - 4 were regiospecifically converted to the corresponding 2-nitro-4-bromo derivatives 5 - 8 in quantitative yields, with Zincke nitration using sodium nitrite. Catalytic hydrogenation of the 2-nitro-4-bromides 5 - 8 over palladium-on-charcoal gave directly the desired 2-amino estrogens 14 - 17 in high yields. The 2-amino compounds 15 and 17 were also obtained by the reduction of the corresponding 2-nitro-4-bromides 6 and 8 with sodium borohydride in the presence of palladium chloride.