Conformational analysis of ephedrine using molecular mechanical, semi-empirical and ab initio quantum mechanical methods

A molecular mechanics conformational analysis was performed on the ionic form of ephedrine using the Dreiding, CVFF and CFF force fields. These calculations were then refined using semi-empirical and ab initio quantum mechanical methods. The results were compared to experimental X-ray data collected in the Cambridge Structural Database (CSD) and to NMR coupling constants. The findings showed that the experimentally accessible conformations are local minima of the isolated molecule rather than the global minimum, access to which is inhibited by an energy barrier for rotation around the OCCN torsion. There is an intra-molecular hydrogen bond between the N+H and OH groups, which dominates the low-energy conformations. The different methods produced similar results but, after comparison with the CSD and NMR information, the ab initio methods are shown to be better at predicting the conformations found by experiment.