Rate-determining nitrogen inversion in the isomerisation of isoimides to imides and azides to tetrazoles: direct observation of intermediates stabilized by trifluoroethyl groups

Abstract

Reaction of N-alkyl- and N-trifluoroalkylbenzimidoyl chlorides 2 in the presence of either acetate or azide ion leads initially to the formation of the corresponding isoimides 4(Z) and imidoyl azides 8(Z) (both of which could be observed spectroscopically). These are formed via nucleophilic trapping of the nitrilium cations 3 in aqueous organic solutions. Subsequently these imidoyl acetates and azides rearrange to the more stable imides 5 or tetrazoles 9. These rearrangements are characterised by a low dependence on solvent polarity and insensitivity to added salts, indicating that the rate-determining step is the isomerisation of the initially formed Z-isomer of the imine to the E-isomer (imine nitrogen inversion) rather than the subsequent N→O acyl group transfer or cyclisation. The Hammett ρ value (−0.4), obtained for the rearrangement of the imidoyl azides to the tetrazoles, compares well to other systems where the rate-determining step (nitrogen inversion) was similar. Nitrogen inversion in these imine systems is therefore significantly slower (ca. 10-fold relative to an ethyl group) in the presence of the trifluoroethyl group on nitrogen.