A modified Polonovski reaction has been employed to N-demethylate several opiate alkaloids in moderate to high yield. This method provides an alternative to traditional N-demethylation procedures which utilize toxic reagents such as cyanogen bromide or expensive reagents such as vinyl chloroformate. The current synthesis involves N-oxide formation, isolation of the corresponding N-oxide hydrochloride, and an FeSO(4).7H(2)O mediated Polonovski reaction to afford the desired secondary amine.

The removal of an N-methyl group, or N-demethylation, is a useful chemical transformation in organic synthesis which has particular importance in the field of alkaloid chemistry. Historically, tertiary N-methyl alkaloids have been N-demethylated using the same methods as for N-dealkylating tertiary amines. Such methodologies have included the von Braun reaction, the use of chloroformate and azodicarboxylate reagents and the Polonovski reaction, amongst others. Photochemical and biochemical procedures have also been successfully employed. This review will examine these N-demethylation procedures, with special emphasis on their application to opiate alkaloids.

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