Further investigation of the N-demethylation of tertiary amine alkaloids using the non-classical Polonovski reaction

The iron salt-mediated Polonovski reaction efficiently N-demethylates certain opiate alkaloids. In this process, the use of the hydrochloride salt of the tertiary N-methyl amine oxide was reported to give better yields of the desired N-demethylated product. Herein, we report further investigation into the use of N-oxide salts in the iron salt-mediated Polonovski reaction. An efficient approach for the removal of iron salts that greatly facilitates isolation and purification of the N-nor product is also described.

Graphical abstractThe iron salt-mediated Polonovski reaction efficiently N-demethylates certain opiate alkaloids. In this process, the use of the hydrochloride salt of the tertiary N-methyl amine oxide was reported to give better yields of the desired N-demethylated product. Herein, we report further investigation into the use of N-oxide salts in the iron salt-mediated Polonovski reaction. An efficient approach for the removal of iron salts that greatly facilitates isolation and purification of the N-nor product is also described.Figure optionsDownload full-size imageDownload as PowerPoint slide