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

Abstract

A mechanochemical approach has been demonstrated for the selective cleavage of nitrogen&ndash;carbon bonds in the <em>N</em>-demethylation of various alkaloids relevant in the pharmaceutical industry. This methodology employs a range of so-called &ldquo;liquid additives&rdquo; used in microliter quantities in liquid assisted grinding rather than &ldquo;solvents&rdquo; 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 <em>N</em>-demethylation process.</span></p>