CONFORMATIONAL EQUILIBRIA OF EPHEDRINE AND PSEUDOEPHEDRINE AND HYDROGEN-BONDING

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.