A DFT Model Reaction and a Procedure for Predicting the Nucleofugality of Tertiary Heterocyclic Amines

Abstract

A previously described procedure for estimating the nucleofugality of substituted pyridines in terms of calc f N parameters has now been applied to various tertiary heterocyclic amines. Geometries of conformers of some 4,4'-bis(dimethylamino)benzhydryl substituted ammonium ions, bearing tertiary heterocyclic amines as leaving groups, and of corresponding heterolytic transition-state conformers have been optimized at the M06-2X/6-311+G(2d,p) level of theory with the IEFPCM implicit solvation model for acetonitrile. Taking into account the existence of multiple parallel paths connecting corresponding conformers of the two states (that is, ground state and transition state), free energies of activation for the model heterolysis of the cationic substrates (ΔG ‡model ) were derived from computed free energies of conformers at 25 °C. Very good correlation between the ΔG ‡model values and corresponding experimental free energies of activation (ΔG ‡ ) taken from the literature indicates that both the applied DFT model reaction and the described procedure provide very good bases for evaluating calc f N nucleofugality parameters of various tertiary heterocyclic amines.