Thebaine reaction with bromine

As in the case of the steroids, introduction of additional nuclear substituents yields morphine analogs of increased potency. The more important of these are derived from one of the minor alkaloids that occur in opium. Thebaine (14), present in crude opium in about one-tenth the amount of morphine, exhibits a reactive internal diene system that is well known to undergo various addition reactions in a 1,4 manner (e.g., bromination). Thus, reaction with hydrogen peroxide in acid may be visualized to afford first the 14-hydroxy-6-hemiketal (15). Hydrolysis yields the isolated unsaturated ketone (16). Catalytic reduction... 

In contrast to bromination of thebaine (137), which gave 14-bromocodeinone (138 R1 + R2 = O), iodination in methanol-chloroform solution produced the 7-iodo-derivative (141 R1 = H, R2 = I).156 The latter was transformed into the indolinocodeine (147 X = OAc) by treatment with silver acetate in acetic acid, thus offering an alternative route to those derivatives which had been previously prepared by solvolysis of 14-bromocodeine (138 R1 = OH, R2 = H). Similarly, treatment of (141 R = H, R2 = I) with silver cyanide and sodium azide afforded compounds (147 X = NC) and (147 X = N3) respectively. This report should stimulate further investigation of the factors involved in yielding predominantly C(14)- or C(7)-substituted products in electrophilic reactions on thebaine.156... 

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