Direct Synthesis of N,N-Dimethylated and β‑Methyl N,N-Dimethylated Amines from Nitriles Using Methanol: Experimental and Computational Studies

Direct and selective
synthesis of N,N-dimethylated amines from
nitriles using methanol as C1 building blocks is reported using an
air- and moisture-stable ruthenium complex. Following this process,
various aromatic as well as aliphatic nitriles were converted to the
corresponding N-methylated amines. Interestingly, tandem C-methylation
as well as N-methylation was achieved by introducing multiple methyl
groups. The practical aspect of this process was revealed by preparative-scale
reactions with different nitriles and the synthesis of anti-allergic
drug “avil”. Several kinetic experiments and detailed
DFT calculations were carried out to understand the mechanism of this
process.