DFT studies of beta-elimination reactions in water solution with different bases: Theory vs experiment

We describe a theoretical investigation of a prototype beta-elimination reaction in systems activated by the pyridine ring. The reactions investigated, the acetohydroxamic-induced and OH--induced beta-elimination with the nitrogen protonated N-[2-(2-pyridyl)ethyl]quinuclidinium Substrate, offers a unique opportunity to test Computational methodologies for the study of beta-elimination reactions in solution since for this system detailed kinetic experimental data have been obtained. We calculated the pK(a)s of the aceto-hydroxamic acid and of the substrate, for which experimental estimates are available. We then thoroughly characterized the reactive free-energy profile. Our study establishes that the reaction proceeds via a quasi reversible Etch mechanism for the reaction induced by acetohydroxamate base, and irreversible E1cb mechanism for the reaction induce by OH- base, involving a stable carbanion intermediate. Except for a discrepancy in the reproduction of the pK(a) of the acetohydroxamic acid and of the H2O, the calculated free-energy profile is in excellent agreement with the experiment, showing the general reliability of the present approach.