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

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

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.
- Teaching ideas,
- S_N2 reaction,
- Quantum chemical calculations,
- Potential energy profiles,
- Solvent effect
1. [1]
  J.A. Marshall, J.D.Trometer, D.G. Cleary, Chem. Rev. 1989, 89, 1503.
2. [2]
  D. Soorukram, P. Knochel, Org. Lett. 2004, 6, 2409.
3. [3]
  M.I. Calaza, E. Hupe, P. Knochel, Org. Lett. 2003, 5, 1059.
4. [4]
  T. Hansen, P. Vermeeren, L.D. Jong, F.M. Bickelhaupt, T.A. Hamlin, J. Org. Chem. 2022, 87, 8892.
5. [5]
  M.B. Smith, March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed., Wiley: New York, NY, USA, 2013.
6. [6]
7. [7]
8. [8]
9. [9]
  T.H. Dunning Jr, J. Chem. Phys. 1989, 90, 1007.
10. [10]
  P.J. Hay, W.R. Wadt, J. Chem. Phys. 1985, 82, 299.
11. [11]
  K. Fukui. Acc. Chem. Res. 1981, 14, 363.
12. [12]
  M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A.G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, et al., Gaussian 09, Revision A.01, Gaussian, Inc.: Wallingford, CT, USA, 2009.
1. [1]
  Hong Wu , Yuxi Wang , Hongyan Feng , Xiaokui Wang , Bangkun Jin , Xuan Lei , Qianghua Wu , Hongchun Li . Application of Computational Chemistry in the Determination of Magnetic Susceptibility of Metal Complexes. University Chemistry, 2025, 40(3): 116-123. doi: 10.12461/PKU.DXHX202405141
2. [2]
  Juan Yang . From qualitative to quantitative taking dipole moment and polarizability as examples: a case of general chemistry in the Chemistry “101 Plan”. University Chemistry, 2026, 41(6): 18-23. doi: 10.12461/PKU.DXHX202605042
3. [3]
  Bing Yuan , Fengli Yu , Congxia Xie . Teaching Cases Design of Catalysis Courses for Emerging Engineering Education. University Chemistry, 2024, 39(3): 191-198. doi: 10.3866/PKU.DXHX202309032
4. [4]
  Juan Yang . Design and writing ideas for the teaching cases of general chemistry in the Chemistry “101 Plan”. University Chemistry, 2026, 41(6): 1-4. doi: 10.12461/PKU.DXHX202605043
5. [5]
  Wanqun Hu , Pingping Zhu , Yuan Zheng , Wanqun Zhang , Wei Shao , Hong Wu , Qiang Zhou , Kaiping Yang , Xiang Sheng . Design and Practice of Ideological and Political Case Study in Instrumental Analysis Experiment Course: the Extraction and Structural Identification of Artemisinin. University Chemistry, 2024, 39(2): 203-207. doi: 10.3866/PKU.DXHX202310062
6. [6]
  Jianfeng Yan , Yating Xiao , Xin Zuo , Caixia Lin , Yaofeng Yuan . Comprehensive Chemistry Experimental Design of Ferrocenylphenyl Derivatives. University Chemistry, 2024, 39(4): 329-337. doi: 10.3866/PKU.DXHX202310005
7. [7]
  Zhengli Hu , Jia Wang , Yi-Lun Ying , Shaochuang Liu , Hui Ma , Wenwei Zhang , Jianrong Zhang , Yi-Tao Long . Exploration of Ideological and Political Elements in the Development History of Nanopore Electrochemistry. University Chemistry, 2024, 39(8): 344-350. doi: 10.3866/PKU.DXHX202401072
8. [8]
  Supin Zhao , Jing Xie . Understanding the Vibrational Stark Effect of Water Molecules Using Quantum Chemistry Calculations. University Chemistry, 2025, 40(3): 178-185. doi: 10.12461/PKU.DXHX202406024
9. [9]
  Ling Fan , Meili Pang , Yeyun Zhang , Yanmei Wang , Zhenfeng Shang . Quantum Chemistry Calculation Research on the Diels-Alder Reaction of Anthracene and Maleic Anhydride: Introduction to a Computational Chemistry Experiment. University Chemistry, 2024, 39(4): 133-139. doi: 10.3866/PKU.DXHX202309024
10. [10]
  Tingbo Wang , Yao Luo , Bingyan Hu , Ruiyuan Liu , Jing Miao , Huizhe Lu . Quantitative Computational Study on the Claisen Rearrangement Reaction of Allyl Phenyl Ethers: An Introduction to a Computational Chemistry Experiment. University Chemistry, 2024, 39(11): 278-285. doi: 10.12461/PKU.DXHX202403082
11. [11]
  Jiaxun Wu , Mingde Li , Li Dang . The R eaction of Metal Selenium Complexes with Olefins as a Tutorial Case Study for Analyzing Molecular Orbital Interaction Modes. University Chemistry, 2025, 40(3): 108-115. doi: 10.12461/PKU.DXHX202405098
12. [12]
  Danwei Zhang . Instructional design for the knowledge points of named reactions in amine synthesis based on the BOPPPS model: selected teaching cases from the “101 plan” organic chemistry curriculum. University Chemistry, 2026, 41(6): 48-52. doi: 10.12461/PKU.DXHX202511060
13. [13]
  Qian Huang , Zhaowei Li , Jianing Zhao , Ao Yu . Quantum Chemical Calculations Reveal the Details Below the Experimental Phenomenon. University Chemistry, 2024, 39(3): 395-400. doi: 10.3866/PKU.DXHX202309018
14. [14]
  Xiaolong Zhang , Mingshan Jin , Shaoli Liu , Bingfei Yan , Yun Li . Constructing High-Precision Potential Energy Surfaces Based on Physical Models: A Comprehensive Computational Chemistry Experiment. University Chemistry, 2025, 40(10): 257-262. doi: 10.12461/PKU.DXHX202411049
15. [15]
  Jiang Liu , Can Hu , Shunli Li . Design and practical exploration of teaching cases for metal-oxygen clusters: an introduction to the inorganic chemistry teaching case under the Chemistry “101 Plan”. University Chemistry, 2026, 41(6): 30-34. doi: 10.12461/PKU.DXHX202510023
16. [16]
  Qun Jing , Xiuhua Cui , Xu Ji , Yi Jiang . Application of Research Case-Based Teaching Method in the Computational Materials Science Course. University Chemistry, 2025, 40(11): 175-183. doi: 10.12461/PKU.DXHX202505050
17. [17]
  Lijun Zhou , Dongmei Wang , Jiameng Wang , Tongjie Yao , Mei Qi , Yin Kong , Yan Song . Teaching Case Design of “Degradation and Aging” as an Ideological and Political Demonstration Course. University Chemistry, 2025, 40(4): 80-86. doi: 10.12461/PKU.DXHX202405113
18. [18]
  Changsheng Lu . Discovering-and-Sharing Model: a Case of the Inorganic Chemistry Course in the Chemistry “101 Plan”. University Chemistry, 2024, 39(10): 78-83. doi: 10.12461/PKU.DXHX202408028
19. [19]
  Dongju Zhang , Rongxiu Zhu . Construction of Ideological and Political Education in Quantum Chemistry Course: Several Teaching Cases to Reveal the Universal Connection of Things. University Chemistry, 2024, 39(7): 272-277. doi: 10.3866/PKU.DXHX202311032
20. [20]
  Jia Zhou . Constructing Potential Energy Surface of Water Molecule by Quantum Chemistry and Machine Learning: Introduction to a Comprehensive Computational Chemistry Experiment. University Chemistry, 2024, 39(3): 351-358. doi: 10.3866/PKU.DXHX202309060

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(94)
HTML views(17)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

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

Metrics

通讯作者: 陈斌, bchen63@163.com

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