A Unified Framework for Understanding Nucleophilicity and Protophilicity in the SN2/E2 Competition

Pascal Vermeeren, Thomas Hansen, Paul Jansen, Marcel Swart, Trevor A. Hamlin*, F. Matthias Bickelhaupt

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


The concepts of nucleophilicity and protophilicity are fundamental and ubiquitous in chemistry. A case in point is bimolecular nucleophilic substitution (SN2) and base-induced elimination (E2). A Lewis base acting as a strong nucleophile is needed for SN2 reactions, whereas a Lewis base acting as a strong protophile (i.e., base) is required for E2 reactions. A complicating factor is, however, the fact that a good nucleophile is often a strong protophile. Nevertheless, a sound, physical model that explains, in a transparent manner, when an electron-rich Lewis base acts as a protophile or a nucleophile, which is not just phenomenological, is currently lacking in the literature. To address this fundamental question, the potential energy surfaces of the SN2 and E2 reactions of X+C2H5Y model systems with X, Y = F, Cl, Br, I, and At, are explored by using relativistic density functional theory at ZORA-OLYP/TZ2P. These explorations have yielded a consistent overview of reactivity trends over a wide range in reactivity and pathways. Activation strain analyses of these reactions reveal the factors that determine the shape of the potential energy surfaces and hence govern the propensity of the Lewis base to act as a nucleophile or protophile. The concepts of “characteristic distortivity” and “transition state acidity” of a reaction are introduced, which have the potential to enable chemists to better understand and design reactions for synthesis.

Original languageEnglish
Pages (from-to)15538-15548
Number of pages11
JournalChemistry - A European Journal
Issue number67
Early online date31 Aug 2020
Publication statusPublished - 1 Dec 2020

Bibliographical note

Special Issue: 1000th Issue (December 1, 2020).


  • activation strain model
  • bond theory
  • density functional calculations
  • nucleophilicity
  • protophilicity


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