Conformational analysis of some unsymmetrically substituted 1,4-dihydropyridines

Semi-empirical PM3 and density functional theory (DFT) B3LYP with 6-31G and 6-31++G∗∗ basis sets methods are used to obtain the equilibrium structures of some symmetrical and unsymmetrically substituted 1,4-dihydropyridines (DHPs), including position of the aryl group conformation with respect to the ester and acetyl groups and deviation of DHP ring from the planarity. Comparative heats of formation of these compounds were also investigated. In addition, the optimum structures of these compounds have been compared with those of the symmetrical 3,5-diacetyl-l,4-dihydropyridines and 1,4-dihydropyridine-3,5-diesters to elucidate the effect of the acetyl and carboethoxy groups in 3- and 5-positions on the optimum conformation of the 1,4-DHPs. Based on the B3LYP/6-31G optimized structures, natural bond orbitals (NBO) charges have been calculated and analyzed for the unsymmetrical 1,4-DHPs. We have finally obtained some conformational rules in terms of the natures and positions of the substituents on the DHP ring.