N-demethylation of alkaloids using nanoscale zero valent iron

Abstract

The N-demethylation of naturally occurring opiate compounds is a necessary step in the synthesis of many pseudo-opioid pharmaceuticals. Such drugs have gained recent media attention in the fight against opiate addiction; hence, the ability to synthesize them efficiently is important. This work aims to improve the N-demethylation of alkaloid precursors through the use of zero valent nanoscale iron in a modified Polonovski reaction. Initial studies performed on dextromethorphan indicate that yields of the demethylated product using a 10 mol % loading of zero valent nanoscale iron are comparable to those achieved by using a stoichiometric amount of commercially available iron (0) dust. The preparation of zero valent nanoscale iron particles and their use in the N-demethylation of dextromethorphan will be described.