Conformations and barriers to inversion of seven-membered cyclic oxamides and their monothio- and dithio-analogues: a study by dynamic nuclear magnetic resonance spectroscopy and molecular mechanics

Abstract

Conformations and barriers to inversion of NN′-dialkylperhydrodiazepine-2,3-dione and its monothio- and dithio-analogues have been studied by ¹H n.m.r. spectroscopy and by molecular mechanics calculations. Experiments as well as calculations indicate that the compounds studied adopt a twist-boat conformation (C₂ symmetry). The inversion of the ring system involves a passage through a C_s structure with a planar s-cis-(thio)oxamide unit. The free energy barriers increase in the order oxamide < monothio-oxamide < dithio-oxamide. The calculations indicate that the dominant part of the barrier is of steric origin; the electrostatic contribution is <20% of the total barrier height.