Thermal 1,3-proton shift reaction and its application for operationally convenient and improved synthesis of α-(trifluoromethyl)benzylamine

This paper describes a synthesis of alpha-(trifluoromethyl)benzylamine via a novel base-free biomimetic reductive amination of alpha,alpha,alpha-trifluoroacetophenone with benzylamine. When the corresponding imine, derived from alpha,alpha,alpha-trifluoroacetophenone and benzylamine was heated at 200 degrees C under N-2 for I day, the thermal 1,3-proton shift reaction took place giving rise to the N-(benzylidene)-alpha-(trifluoromethyl)benzylamine in quantitative yield. This thermal 1,3-proton shift reaction was used a key step in the development of new and substantially simplified, practical and operationally convenient procedure for preparation of the target alpha-(trifluoromethyl)benzylamine on large scale. (c) 2007 Elsevier B.V. All rights reserved.