Shapeshifting Nucleophiles HO^-(NH₃) React with Methyl Chloride

The microsolvated anions HO^-(NH₃) were found to induce new nucleophile NH₂^-(H₂O)(NH₃) via intramolecular proton transfer. Hence, the ion-molecule nucleophilic substitution (S_N2) reaction between CH₃Cl and these shapeshifting nucleophiles lead to both the HO^- path and NH₂^- path, meaning that the respective attacking nucleophile is HO^- or NH₂^-. The CCSD(T) level of calculation was performed to characterize the potential energy surfaces. Calculations indicate that the HO species are lower in energy than the NH₂ species, and the S_N2 reaction barriers are lower for the HO^- path than the NH₂^--path. Incremental solvation increases the barrier for both paths. Comparison between HO^-(NH₃) and HOO^-(NH₃) confirmed the existence of an α-effect under microsolvated conditions. Comparison between HO^-(NH₃) and HO^-(H₂O) indicated that the more polarized H₂O stabilizes the nucleophiles more than NH₃, and thus, the hydrated systems have higher S_N2 reaction barriers. The aforementioned barrier changes can be explained by the differential stabilization of the nucleophile and HOMO levels upon solvation, thus affecting the HOMO-LUMO interaction between the nucleophile and substrate. For the same kind of nucleophilic attacking atom, O or N, the reaction barrier has a good linear correlation with the HOMO level of the nucleophiles. Hence, the HOMO level or the binding energy of microsolvated nucleophiles is a good indicator to evaluate the order of barrier heights. This work expands our understanding of the microsolvation effect on prototype S_N2 reactions beyond the water solvent.