Theoretical study on the thermal isomerization reaction between meso and DL cyclomers of 4a,6a,10a,10b-tetrahydropyrido-[2,1-c]pyrido[1,2-a]piperazine and its lower homologue

The reaction mechanism of thermal isomerization from a meso to a DL cyclome r of the titled compounds has been studied theoretically using ab initio RH F, GVB, and MCSCF methods with 6-31G(d) and TZV(d,p) basis sets, followed b y the second-order Moeller-Plesset perturbation (MP2) calculations. In 4a,6 a,10a, 10b-tetrahydropyrido[2,1-c]pyrido[1,2-a]piperazine (1), it is shown that the energy barrier from a singlet diradical intermediate to the DL cyc lomer is smaller than that of the meso cyclomer by 3 kcal/mol. Concomitantl y, the transition-state structure for the latter case is spatially three ti mes far apart from the intermediate in comparison with that for the former case. This suggests the preference for a formation of the DL cyclomer over the meso cyclomer. On the other hand, it is shown in 4a,4b,8a,9a-tetrahydro pyridino[1',2'-4,3]imidazolidino[1,5-a]pyridine (2) that no thermal isomeri zation reaction should take place from the meso to the Dr. cyclomer. This i s because there is essentially no energy barrier from the intermediate to t he meso cyclomer but an energy barrier of about 10 kcal/mol from the interm ediate to the DL cyclomer. Besides, the transition-state structure for the latter case is spatially far apart in comparison with that for the former c ase. The present findings are compatible with the available experimental in formation. (C) 2000 Elsevier Science B.V. All rights reserved.