My new favorite, the Eschweiler–Clarke reaction!

The Eschweiler–Clarke reaction (also called the Eschweiler–Clarke methylation) is a chemical reaction whereby a primary (or secondary) amine is methylated using excess formic acid and formaldehyde. Reductive amination reactions such as this one will not produce quaternary ammonium salts, but instead will stop at the tertiary amine stage. It is named for the German chemist Wilhelm Eschweiler (1860–1936) and the British chemist Hans Thacher Clarke (1887-1972).

The mechanism of the reaction is really simple, first methylation of the amine begins with imine formation with formaldehyde. The formic acid acts as a source of hydride and reduces the imine to a secondary amine. The driving force is the formation of the gas carbon dioxide. Formation of the tertiary amine is similar, but slower due to the difficulties in iminium ion formation.

The only problem was, that the yields were at a maximum 60%, but for the first run it’s not that bad.

9:31 pm • 16 July 2014 • 164 notes • View comments