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Solvent Molecule-Induced Competitive Ion-Molecule Nucleophilic Substitution Reactions Involving an α‑Nucleophilic
Gang Fu1, Siwei Zhao2, Hongyi Wang3
1Key Laboratory of Chemistry and Chemical Engineering on Heavy-Carbon Resources, School of Chemistry and Chemical Engineering, Yili Normal University, Yining 835000, P. R. China.
ACS Omega
|July 28, 2026
Summary
The hydroperoxide anion (HOO-) is more reactive than the methoxide anion (CH3O-) in reactions with methyl bromide (CH3Br). This enhanced reactivity is due to the α-effect nucleophile nature of HOO-, influenced by solvent interactions.
Area of Science:
- Physical Chemistry
- Computational Chemistry
- Reaction Mechanisms
Background:
- Microsolvent conditions can alter nucleophile reactivity.
- The hydroperoxide anion (HOO-) can abstract protons from methanol (CH3OH), forming the methoxide anion (CH3O-).
- Competition exists between direct HOO- substitution and proton transfer (PT)-induced CH3O- substitution.
Purpose of the Study:
- To explore the competition between the direct HOO--SN2 pathway and the PT-induced CH3O--SN2 pathway.
- To investigate the role of solvent molecules (CH3OH) on the reactivity of HOO- and CH3O- with methyl bromide (CH3Br).
- To understand the α-effect nucleophile's nature and solvent effects on enhanced reactivity.
Main Methods:
- Quantum chemistry calculations were employed.
- Potential energy profiles for HOO-(CH3OH)n and CH3O-(HOOH)0,1(CH3OH)n-1 reacting with CH3Br were analyzed.
- Activation strain analysis was used to compare reaction pathways.
Main Results:
- The direct HOO--SN2 pathway has lower energy barriers (0.4-3.8 kcal/mol) than the CH3O--SN2 pathway.
- Stronger interaction energy and orbital interactions stabilize the transition state of the HOO--SN2 pathway.
- Increased hydration raises barrier heights, but the PT-induced CH3O--SN2 pathway is significantly suppressed.
Conclusions:
- HOO-(CH3OH)n exhibits enhanced reactivity compared to CH3O-(HOOH)0,1(CH3OH)n-1 nucleophiles.
- The enhanced reactivity is attributed to the α-nucleophilic character of the HOO- anion.
- Solvent molecules play a crucial role in enhancing the reactivity of α-effect nucleophiles.
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