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

We describe a theoretical investigation of a prototype β-elimination reaction in systems activated by the pyridine ring. The reactions investigated, the acetohydroxamic-induced and OH−-induced β-elimination with the nitrogen protonated N-[2-(2-pyridyl)ethyl]quinuclidinium substrate, offers a unique opportunity to test computational methodologies for the study of β-elimination reactions in solution since for this system detailed kinetic experimental data have been obtained. We calculated the pKas of the acetohydroxamic 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 E1cb 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 pKa 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.