Catalytic N-Dealkylation of Tertiary Amines - A Biomimetic Oxygenation Reaction

Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Ardsley, N.Y. 10502, U.S.A.

A heterogeneous catalyst system is described for N-dealkvlation of tertiary amines. A large number of tertiary amines including some important synthetic drugs were N-dealkylated to give the corresponding secondary amines in 50-65% yields. The reaction was carried out at room temperature by stirring a solution of a tertiary amine in methanol containing 10% palladium-on-charcoal catalyst. The reaction had absolute requirement for molecular oxygen like the enzymatic dealkylation reaction. It also needed methanol to act as the reductant of molecular oxygen like the NADPH in the enzymatic reaction. A catalytic cycle similar to cvtochrome P-450-catalysed oxygena­tion cycle is proposed for activation and transfer of oxygen to the α-carbon of tertiary amines to give unstable carbinolamines which on dissociation yield secondary amines.