N-demethylation of alkaloids using nanoscale zero valent iron

1 online resource (x, 48 p.) : ill. (some col.)Includes abstract.Includes bibliographical references (p. 42-48).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

Liquid Assisted Grinding for the <i>N</i>‑Demethylation of Alkaloids

A mechanochemical approach has been demonstrated for the selective cleavage of nitrogen–carbon bonds in the <i>N</i>-demethylation of various alkaloids relevant in the pharmaceutical industry. This methodology employs a range of so-called “liquid additives” used in microliter quantities in liquid assisted grinding rather than “solvents” used in solution phase reactions. Green liquid additives such as alcohols, water, PEG and ionic liquids as well as a nonchemical, mechanical approach for the generation of nanoscale Fe⁰ dust significantly improve the green attributes of the <i>N</i>-demethylation process