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 α-(trifluoromethyl)benzylamine via a novel base-free biomimetic reductive amination of α,α,α-trifluoroacetophenone with benzylamine. When the corresponding imine, derived from α,α,α-trifluoroacetophenone and benzylamine was heated at 200 °C under N2 for 1 day, the thermal 1,3-proton shift reaction took place giving rise to the N-(benzylidene)-α-(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 α-(trifluoromethyl)benzylamine on large scale.