5-Hydroxycyclooctanone–hemiacetal rearrangement: ab initio mechanistic study

Abstract

Ab initio theoretical studies are carried out to investigate the relationship between reactivity and conformation in 5-hydroxy cyclooctanone. Calculations at MP2/6-31G* and B3LYP/6-31G* levels are reported along with AIM calculations for critical points of vanishing density gradients. AIM results establish interaction between the carbonyl carbon and the nucleophilic oxygen from the hydroxyl group. The transition state geometry is investigated in detail. The analysis indicates that the geometric locations of the atoms involved in one of the local minima of 5-hydroxy cyclooctanone are conveniently arranged for the cyclization. Intrinsic reaction coordinate profile is obtained to monitor the intramolecular nucleophilic attack of the hydroxyl group at the C atom of the carbonyl moiety with a concerted shift of H atom from the hydroxyl group to the carbonyl oxygen. Thermodynamic data from Hessian calculations indicate much higher stability of the cyclized hemiacetal formed. The same degree of thermodynamic stability of the cyclized product may not be possible if such a geometric arrangement is not available.