Module 4: Formation of Aliphatic Carbon-Nitrogen Bonds

Lecture 10 : Carbon-Nitrogen Bonds Formation - I

4.3.1.2 Eschweiler-Clarke (Clark) Methylation

Secondary amines could be readily methylated using the combination of formaldehyde and formic acid under heating. This process has been extensively used in total synthesis (Scheme 9).

Scheme 14

Examples: