Liquid Assisted Grinding for the N-Demethylation of Alkaloids

A mechanochemical approach has been demonstrated for the selective cleavage of nitrogen–carbon bonds in the N-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 N-demethylation process.