The synthesis and conformational analysis of tetrahydro-1,2,4-oxadiazines

Abstract

The synthesis and variable temperature 1H and 13C NMR spectra of three tetrahydro-1,2,4-oxadiazines are reported. The N(4)-Me inversion barriers are 6.8–7.0 (ax→ts) and 7.4–7.9 kcal mol −1 (eq→ts) with ΔG° 0.6–0.9 kcal mol −1. The N(2)-Me inversion barriers are 10.4–11.4 (ax→ts) and 11.6–13.1 kcal mol −1 (eq→ts) with ΔGδ 1.2–1.7 kcal mol −1. The barrier to ring inversion is ca. 12.7 kcal mol −1. “R value” analysis shows the ring to have a 56.5±2δ dihedral angle about the C(5)-(6) bond, indicative of the expected chair conformation.