Illustrated Glossary of Organic Chemistry

Exhaustive methylation: The process of alkylation with methyl groups until all possible methylations have been achieved.

In the Hofmann elimination reaction sequence, exhaustive methylation (shown in red) converts an amine to an alkylammonium salt prior to E2 elimination.


Exhaustive methylation has been used in natural product structural analysis. For example, if one mole of an unknown alkaloid (represented here by nicotine) reacts with two moles of methyl iodide, we can conclude the alkaloid contains two site for methylation.