Conformational equilibria of ephedrine and pseudoephedrine and hydrogen bonding

Abstract

Proton NMR spectra suggest that the conformation with trans vicinal hydrogens is favored for ephedrine as the free base in deuterium oxide, although in non-polar solvents, such as deuteriotrichloromethane, the gauche vicinal hydrogen conformations are favored, as has been reported previously. The conjugate acid has primarily gauche hydrogens. In contrast, the trans-hydrogen rotamers of pseudoephedrine dominate for both the non-protonated and protonated forms in deuterium oxide. Hydrogen bonding is unlikely to be as important as usually assumed in determining the conformational preferences of these substances.