A Unified Framework for Understanding Nucleophilicity and Protophilicity in the S(N)2/E2 Competition

The concepts of nucleophilicity and protophilicity are fundamental and ubiquitous in chemistry. A case in point is bimolecular nucleophilic substitution (S(N)2) and base‐induced elimination (E2). A Lewis base acting as a strong nucleophile is needed for S(N)2 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 S(N)2 and E2 reactions of X(−)+C(2)H(5)Y 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.