Solvent Molecule-Induced Competitive Ion-Molecule Nucleophilic Substitution Reactions Involving an α‑Nucleophilic...

Under microsolvent conditions, when the α-nucleophile HOO^- reacts with CH₃Br, it can abstract a proton from the solvent CH₃OH to induce alternative nucleophile CH₃O^-(HOOH). In the present work, the competition between the normal HOO^--S_N2 pathway and the photon transfer (PT)-induced CH₃O^--S_N2 pathway has been explored by quantum chemistry calculations for HOO^-(CH₃OH) _n and CH₃O^-(HOOH)_0,1 (CH₃OH) _n-1 reacting with CH₃Br. The potential energy profile of the HOO^--S_N2 pathway exhibits that the energy barriers of the traditional back-side attack substitution are 0.4-3.8 kcal/mol lower than those of the CH₃O^--S_N2 pathway, suggesting the HOO^-(CH₃OH) _n is more active, which is consistent with the experimental phenomenon. The activation strain analysis suggests compared to the CH₃O^--S_N2 pathway, the stronger interaction energy between the HOO^-(CH₃OH) and CH₃Br over the entire reaction course stabilizes its transition state, which is caused by the stronger orbital interaction of the HOO^--S_N2 pathway. The barrier heights of both pathways are increased with the incremental hydration, but the PT-induced CH₃O^--S_N2 pathway is highly suppressed. The enhanced reactivity of reactions involving HOO^-(CH₃OH) _n is found through comparison with CH₃O^-(HOOH)_0,1(CH₃OH) _n-1 nucleophiles and is ascribed to the α-nucleophilic character of the HOO^- anion. This work deepens an understanding of the nature of the α-effect nucleophile and highlights the effect of the solvent molecule on the enhanced reactivity.