计算化学驱动S<sub>N</sub>2反应教学改革——竞争性反应路径的量化分析与教学实践

引用本文: 刘旭, 吴承雪, 李辉, 吴阳. 计算化学驱动S_N2反应教学改革——竞争性反应路径的量化分析与教学实践[J]. 大学化学, 2026, 41(7): 441-448. doi: 10.12461/PKU.DXHX202504109 shu

Citation: Xu Liu, Chengxue Wu, Hui Li, Yang Wu. Computational chemistry-driven teaching reform of S_N2 reactions: quantitative analysis of competitive reaction pathways and pedagogical practice[J]. University Chemistry, 2026, 41(7): 441-448. doi: 10.12461/PKU.DXHX202504109 shu

计算化学驱动S_N2反应教学改革——竞争性反应路径的量化分析与教学实践

刘旭 ,
吴承雪 ,
李辉 ^, ,
吴阳 ^,

辽宁大学化学院, 辽宁沈阳 110036

通讯作者: 李辉,Email:lihui@lnu.edu.cn; 吴阳,Email:wuyang@lnu.edu.cn

基金项目:
国家自然科学基金(22203039,22473051)

辽宁大学本科教学改革项目(JG2024PTXM10)

摘要: 亲核取代反应(S_N2)是基础有机化学的核心教学内容，但传统教学对烯丙基S_N2'反应的讨论不足，导致学生普遍存在“S_N2是唯一可能路径”的认知偏差。本研究以CH₃S^-/CH₃O^- + CH₂=CHCH₂Br为教学模型体系。采用M06-2X方法和SMD溶剂模型进行理论计算，定量分析了S_N2与S_N2'反应的竞争关系。研究结果表明，在气相和水溶剂中，S_N2反应路径的活化能垒显著低于S_N2'反应，且水环境使二者能垒明显增加，但未改变路径选择性。进一步分析揭示，溶液中几何畸变率大幅增加导致溶液中更高的活化能垒。特别地，水溶剂环境使CH₃S^-的亲核性强于CH₃O^-，这与硫原子更小的几何畸变增幅密切相关。在教学实践中，通过展示过渡态结构演变和势能曲线特征，使学生对竞争性路径深入理解。本研究不仅为亲核取代反应教学提供了量化分析模式，更建立了“量化计算-结构分析-结果讨论”的教学方法，为计算化学融入本科教学提供了成功案例。

关键词:

English

Computational chemistry-driven teaching reform of S_N2 reactions: quantitative analysis of competitive reaction pathways and pedagogical practice

College of Chemistry, Liaoning University, Shenyang 110036, Liaoning Province, China

Corresponding author: Hui Li, ; Yang Wu,

Received Date: 29 April 2025
Revised Date: 19 June 2025
Available Online: 22 September 2025

Abstract: Nucleophilic substitution (S_N2) reactions constitute a core component of fundamental organic chemistry education. However, conventional teaching approaches often inadequately address allylic S_N2' reactions, resulting in students’ prevalent misconception that the S_N2 pathway represents the exclusive reaction mechanism. This study employs the CH₃S^-/CH₃O^- + CH₂=CHCH₂Br system as a pedagogical model, utilizing M06-2X methodology with SMD solvation models to quantitatively examine the competition between S_N2 and S_N2' pathways. Computational results reveal that the S_N2 pathway maintains significantly lower activation barriers than S_N2' in both gas phase and aqueous solution, with aqueous solvation substantially increasing the energy barriers for both pathways while preserving their relative selectivity. Further analysis demonstrates that the elevated barriers in solution arise from increased geometric distortion during the reaction process. Notably, aqueous conditions enhance the nucleophilicity of CH₃S^- relative to CH₃O^-, which correlates with sulfur’s smaller solvation-induced geometric distortion. Through visualization of transition state evolution and potential energy profiles, this approach facilitates students’ mechanistic understanding of competitive reaction pathways. The study establishes an effective “quantitative calculation-structural analysis-discussion” pedagogical framework, providing a successful case study for integrating computational chemistry into undergraduate chemistry education.

Key words:

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沈阳化工大学材料科学与工程学院沈阳 110142

计算化学驱动S_N2反应教学改革——竞争性反应路径的量化分析与教学实践

通讯作者: 李辉,Email:lihui@lnu.edu.cn; 吴阳,Email:wuyang@lnu.edu.cn

English

Computational chemistry-driven teaching reform of S_N2 reactions: quantitative analysis of competitive reaction pathways and pedagogical practice

Corresponding author: Hui Li, ; Yang Wu,

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计算化学驱动SN2反应教学改革——竞争性反应路径的量化分析与教学实践

通讯作者: 李辉,Email:lihui@lnu.edu.cn; 吴阳,Email:wuyang@lnu.edu.cn

English

Computational chemistry-driven teaching reform of SN2 reactions: quantitative analysis of competitive reaction pathways and pedagogical practice

Corresponding author: Hui Li, ; Yang Wu,

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