Can we predict the conformational preference of amides?

To what extent, if any, is the conformation of secondary amides revealed by theory? This question has now been addressed by computational methods usin g calculations at the B3LYP/6-31G* level of theory and H-1 NMR spectroscopy . Both gas-phase and solvent studies predict a Z-anti conformation to be th e lowest in energy for an evaluated series of acetamides. Moreover, Z-anti conformations may also be inferred from the chemical shifts of the N-CH alp ha protons determined by NMR spectroscopy. Thus, a proton situated anti to the N-H proton consistently appears similar to0.8 ppm further downfield tha n a proton situated gauche to the N-H proton. This finding, which could onl y be derived by using the DFT calculations of conformational preference as a guide to interpret the NMR data, might prove to be useful as a simple and convenient methodology for establishing amide conformation experimentally.