Eschweiler-Clark reductive alkylation of amines

A useful application is the Clark-Eschweiler reductive alkylation of amines. Heating a primary or secondary amine with formaldehyde and formic acid results in complete methylation to the tertiary amine. The hydride acceptor is the iminium ion resulting from condensation of the amine with formaldehyde. 

The reductive alkylation of amines is called the Leuckart-Wallach reaction [112-115]. The primary or secondary amine reacts with the ketone or aldehyde. The formed imine is then reduced with formic acid as hydrogen donor (Scheme 20.27). When amines are reductively methylated with formaldehyde and formic acid, the process is termed the Eschweiler-Clarke procedure [116, 117]. 

Amine synthesis from reductive amination of a ketone and an amine in the presence of excess formic acid, which serves as the reducing reagent by delivering a hydride. When the ketone is replaced by formaldehyde, it becomes Eschweiler-Clarke reductive alkylation of amines. 

Brewer, A. R. E. Eschweiler-Clarke reductive alkylation of amine. In Name Reactions for Functional Group Transformations-, Li, J. J., Corey, E. J., eds. John Wiley Sons Hoboken, NJ, 2007, pp 86-111. (Review). 

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