Acetamides of 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocine (benzomorphan), 5,6.7,8,9,10-hexahydro-6,9-methanobenzocyclo-octene, and 6,7,8,9,10,11-hexahydro-7,10-methanocyclo-octa[b][1]benzothiophene as potential selective opioid analgesics

Abstract

The acetate of 5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclo-octen-11-one oxime (13) was reduced with zinc dust in a mixture of acetic acid and acetic anhydride, to give exclusively syn-11-acetamido-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclo-octene (3). By contrast, the acetate (17) of 6,7,8,9,10,11-hexahydro-7,10-methanocyclo-octa[b][1]benzothiophen-12-one oxime (16) gave a mixture of the syn-(6)(28% yield) and anti-12-acetamido-derivatives (10)(25%). The three amides (3), (6), and (10) were hydrolysed with acid to the corresponding amines (4), (7), and (11) and reduced with lithium aluminium hydride to the correspondingN-ethyl derivatives (5), (8), and (12) respectively. Reduction with sodium borohydride in methanol of 6,7,8,9,10,11 -hexahydro-7,10-methanocyclo-octa[b][1]benzothiophen-12-one (15) gave exclusively the syn-alcohol (9). 11α-Acetamido-3,6-dimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocine (1) was prepared by reduction in acetic acid–acetic anhydride of 3,6-dimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-11-one (19) oxime, prepared by adaptation of a procedure due to Belleau.