Synthesis and analgesic activity of some 14 beta-substituted analogues of morphine

Treatment of 14 beta-nitrocodeinone with sodium borohydride gave the codeine derivative which was reduced with zinc dust in acetic anhydride-acetic acid solution to give 14 beta-acetamidocodeine 6-acetate. 14 beta-Thiocyanatocodeinone was obtained from the reaction of thebaine with thiocyanogen and was reduced to 14 beta-mercaptocodeine with lithium aluminum hydride. 14 beta-Bromo- and 14 beta-chlorocodeinone were prepared by the reaction of thebaine with N-bromosuccinimide and N-chlorosuccinimide, respectively. These 14 beta-substituted codeine and codeinones were O-demethylated to the corresponding morphine analogues with boron tribromide. With the exception of 14 beta-nitromorphinone, which was weak in activity, all the other 14 beta-substituted morphine derivatives were approximately equal in potency to normorphine in the guinea pig ileum preparation.