Conformational Analysis Part 26—An Objective Method for Determining Conformer Populations and Coupling Constants in NMR Spectroscopy

Abstract

An objective method of obtaining conformer populations and coupling constants from molecules rapidly interconverting between a number of conformers is given. The method relies on the acquisition of a sufficient data set by varying the solvent and/or temperature until the system is over-determined with more equations than unknowns. No assumptions concerning either the conformer populations or couplings are necessary. The general conditions for an over-determined data set are derived for systems interconverting between two and three conformers, and illustrative examples are given of 1,2-dichloro-1-fluoroethane (1) 1,1,2-trifluoroethane (2) and trans-2-fluoro-3-hydroxy-tetrahydronaphthalene (3). The analysis of the vicinal H–H and H–F couplings of 1 in seven solvents of different polarities gave the couplings and relative energies of the three interconverting conformers. Extrapolation to the vapour using solvation theory gives ΔE (g→t) = 0.8 kcal mol−1 and ΔE (g′→t) = 1.1 kcal mol−1 (1 kcal = 4.184 kJ). A similar analysis of the solvation dependence of the vicinal couplings of 2 shows that the vicinal F–F couplings cannot be used to derive the conformer energies. An alternative treatment based on solvation theory gives the vicinal H–H and H–F couplings in the two interconverting conformers. The direct analysis of the solvent dependence of the couplings of 3 in seven solvents gives the conformer couplings in the two equilibrating half-chair conformers and the energy differences ΔE (ax, ax→eq, eq) which vary from 1.2 kcal mol−1 in CCl4 solution to 0.21 kcal mol−1 in DMSO.