Eschweiler–Clarke reaction

The Eschweiler- Clarke methylation (or simply: Eschweiler- Clarke reaction ) is a name reaction in organic chemistry and named after its developers, the German chemist Wilhelm Eschweiler ( 1860-1936 ) and the British biochemist Hans Thacher Clarke ( 1887-1972 ). They can be considered as a special case of the Leuckart -Wallach reaction with formaldehyde as the alkylating reagent and is used for methylation of primary or secondary amines are used.

Mechanism

As the methylating agent is formaldehyde, which is used in excess, together with an excess of formic acid. In the first reaction step, the nitrogen of the amine attacks the carbonyl carbon of one of the formaldehyde to nucleophilic. The result is the compound 2, which is initially protonated by the formic acid to the oxygen. In two further steps, a water molecule is cleaved, followed by the transfer of a hydride ion takes place with formation of carbon dioxide. The desired methylated amine 6 is formed. The mechanism by which the Leuckart - Wallach reaction identical.

The driving force of the reaction is the formation of carbon dioxide. There is no formation of quaternary ammonium salts, as the tertiary amines formed can not further react with formaldehyde to form imines. Herein lies their advantage over the methylation of haloalkanes such as methyl iodide. If chiral amines, the reaction proceeds normally starting with retention of stereo information.