The synthesis of some novel N-chloro-Δ1-4-azasteroids by efficient N-chlorination of azasteroid lactams with trichloroisocyanuric acid

Abstract

The preparation of N-chloro-Δ1-4-azasteroids 2a–2c from lactams 1a–1c was achieved conveniently and in high yield with trichloroisocyanuric acid. The treatment of 20β-hydroxy-4-aza-5α-pregn-1-en-3-one (1d) with this reagent produced the less stable N-chloro compound 2d, which reacted further to afford 4-aza-5α-pregn-1-en-3,20-dione (4) as the principal product. The similar chlorination of 4-azacholest-5-en-3-one (5) occurred at C-6, giving 6-chloro-4-azacholest-5-en-3-one (6). Photolysis of N-chloro-4-aza-5α-cholest-1-en-3-one (2a) in methanol produced the transient N-acyl imine 7, which was trapped by the solvent to afford 5-methoxy-4-azacholest-1-en-3-one (8), along with 4-azacholesta-1,5-dien-3-one (9) and its 6-chloro derivative 10. Key words: N-chloroazasteroid, Δ1-4-azasteroid, N-chloro-Δ1-4-azasteroid, trichloroisocyanuric acid, N-chlorination.