Rate-Determining Role of Strain for Nitrogen Inversion in Polycyclic Tertiary Amines1

Abstract

The nitrogen inversion barriers for N-isopropyl-, N-butyl-, N-isobutyl-, and N-tert-butyl-7-azabicyclo[2.2.1]heptanes were measured using dynamic NMR line shape analysis. These barriers as well as those for different bicyclic and tricyclic tertiary amines were analyzed via the molecular mechanics method (MM3 force field). A new MM3 steric energy-based parameter, including the energy of substitution-induced disturbances (Esid), is proposed for the estimation of relative strain among related compounds with one variable substituent. A linear relationship was found between N-inversion barriers and this parameter for 7-azabicyclo[2.2.1]heptanes with a β-unbranched N-substituent, which allows an accurate prediction of the barrier values for these amines. For all polycyclic systems studied, the change of strain in the transition state relative to the ground state of the amine, simulated by MM3, makes up 76−106% of the experimental value of the corresponding N-inversion barrier. Among these amines some azabicycles (“bicyclic effect” systems) display the largest deviation (∼25%) from the experimental barrier value. From the point of view of the classical model, this deviation may be attributed to a bicyclic effect which would have an orbital origin.