N-Methyl stereochemistry in tropinone: the conformational flexibility of the tropane motif

Abstract

The intrinsic conformational and structural properties of the tropinone azabicycle have been investigated in a supersonic jet expansion using rotational spectroscopy. The spectrum revealed the presence of equatorial and axial conformers originated by the inversion of the N-methyl group, with the tropane motif adopting a distorted chair configuration. The determination of substitution and effective structures for the two conformers reveals the flexibility and structural changes associated with the N-methyl inversion, mostly a flattening at the nitrogen atom and a simultaneous rising of the carbonyl group in the axial form. Relative intensity measurements indicate that the conformational equilibrium is displaced towards the equatorial form, with a relative population in the jet of N_eq/N_ax ≈ 2/1, which would correspond to a relative energy of ca. 2 kJ mol⁻¹ in pre-expansion conditions. Supporting ab initio calculations of the molecular properties and inversion barrier complemented the experimental work.