RING CONFORMATION AND ESTER ORIENTATION IN DIHYDROPYRIMIDINECARBOXYLATES - A COMBINED THEORETICAL (AB-INITIO, DENSITY-FUNCTIONAL) AND X-RAYCRYSTALLOGRAPHIC STUDY

Ab initio (RHF and MP2) and density functional (B3LYP) calculations wi th basis sets ranging from 3-21G() up to 6-31 + G** on dihydropyrimid ine-5-carboxylates 4 are performed. At all levels of theory a slight p reference (approximate to 1 kcal mol(-1)) for a cis ester orientation (4a) is found, as proposed for the receptor-bound geometry in biologic ally active dihydropyrimidine derivatives. For the ring conformation a strong dependence on the computational procedure is observed, Calcula tions with basis sets lacking polarization functions on first row heav y atoms (3-21G(), 6-31G, 6-311G) lead to planar ring geometries. Incl usion of polarization functions yields puckered boat conformations, Th e puckering amplitudes increase in the order Q(RHF) < Q(B3LYP) < Q(MP2 ). With MP2 unrealistically strong deviations from planarity are predi cted. By single-crystal X-ray analysis an almost planar ring conformat ion is found. Energy differences between planar and puckered geometrie s are negligible with RHF and B3LYP ( < 1 kcal mol(-1)), whereas with MP2 somewhat larger Delta E values (1.5-2.6 kcal mol(-1)) an calculate d, especially when diffuse functions are included. (C) 1998 Elsevier S cience B.V. All rights reserved.