The Nitrogen Inversion Barrier of 7-Methyl-7-azabicyclo[2.2.1]heptane and the “Bicyclic Effect”

Abstract

The free energy of activation for nitrogen inversion of the title compound was determined to be 13.77 (4) kcal/mol at 25 °C in CDCl3 by dynamic 13C NMR and that for the 7-ethyl compound to be 13.17 (4) kcal/mol under the same conditions. The change in α(av) (the average of the three bond angles at nitrogen) during nitrogen inversion is used to assist comparison of inversion barriers for amines with different substituents attached. Comparison with literature data and AM1 calculations indicate that the barrier increase for 7-methyl-7-azabicyclo[2.2.1]heptane N inversion relative to an α-unbranched monocyclic compound of the same pyramidality at nitrogen is on the order of 3.5 kcal/mol, while the less strained 1-bridge-azabicyclo[3.3.1]nonyl and -[3.2.1]octyl systems show barrier increases of about 1.5 kcal/mol. This represents an estimate of the size of Lehn's “bicyclic effect”. © 1989, American Chemical Society. All rights reserved.