Conformational analysis of cyclic amines using carbon-13 chemical shift measurements: dependence of conformation upon ionisation state and solvent

Abstract

Using observations on model compounds a set of substituent shift parameters has been derived which can be used to predict the 13C chemical shifts and protonation shifts of the conformers of cyclohexylarnine derivatives. Large differences are predicted between the spectra of the different conformers and, therefore, the conformational equilibria of these compounds can be determined from the observed chemical shifts of their 13C resonances. The limit on the accuracy of the method is at present ±2% for conformers with small conformational free-energy differences but may be further improved by increased understanding of 13C chemical shifts. The present accuracy is sufficient to enable the effects of ionisation state and solvent on the conformation to beinvestigated. An increase in ΔG of 1.6 kJ mol–1 is observed upon changing from cyclohexane to D2O as solvent and a further increase of 1.2 kJ mol–1 is measured upon protonation of the NH2 group.