A DFT investigation of base-catalyzed beta-elimination reactions in water solution for systems activated by the pyridine ring: Theory vs. experiment

We report a theoretical investigation of beta-elimination reactions in systems activated by the pyridine ring. The investigated reaction, the acetohydroxamate-induced beta-elimination in protonated N-[ 2-(2-pyridyl) ethyl] quinuclidinium, offers a unique opportunity to test computational methodologies since detailed kinetic experimental data are available. We calculated the pK(a)s of the acetohydroxamic acid and the substrate and thoroughly characterized the reactive free-energy profile. The reaction proceeds via a stable carbanion intermediate. Except a discrepancy in the reproduction of the pK(a)s of the acetohydroxamic acid, the calculated free-energy profile is in excellent agreement with the experiment, showing the general reliability of the present approach. (C) 2008 Elsevier B. V. All rights reserved.