A Unified Framework for Understanding Nucleophilicity and Protophilicity in the S_N2/E2 Competition

Abstract

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.

Suppressing carboxylate nucleophilicity with inorganic salts enables selective electrocarboxylation without sacrificial anodes

“…S17 †). 77,78 The acid-to-S N 2 ratios here are not perfectly intrinsic values since in some of the experiments, especially when using benzylic halides, there was also substrate and product oxidation. Moreover, the acid-to-S N 2-ratio can also be sensitive to how long the reaction mixture remains in the cell before workup since S N 2 reactions can happen in the absence of current.…”

Not Carbon s–p Hybridization, but Coordination Number Determines C−H and C−C Bond Length

“…Importantly, our analyses also shed light on the nature, especially the orbital energy, of the σ*‐orbital of the sp n ‐hybridized R n C−X bonds (n = 3, 2, 1; X = H, alkyl, halogen, etc. ), which is of direct relevance for understanding various types of reactions and supramolecular aggregates featuring these bonds [32–34] . We find that the σ*‐orbital of R n C−X bonds becomes increasingly more stabilized, on going from sp 3 to sp 2 to sp carbon centers, again, due to a reduction in the number of substituents around the pertinent carbon atom.…”

“…), which is of direct relevance for understanding varioust ypes of reactionsa nd supramolecular aggregates featuring these bonds. [32][33][34] We find that the s*-orbital of R n CÀXb onds be- comes increasingly more stabilized, on going from sp 3 to sp 2 to sp carbon centers, again,d ue to ar eduction in the number of substituents aroundt he pertinent carbon atom. The s*-orbital of the sp n -hybridized R n CÀHb ond lowers in energy alongn = 3, 2, 1, from 1.7 eV for R 3 CÀHt o1 .4 eV for R 2 CÀHt o1 .0 eV for RCÀH, respectively,b ecauset he R n CC SOMO becomesg radually more stabilized.…”

A benchmark ab initio study of the complex potential energy surfaces of the OH− + CH3CH2Y [Y = F, Cl, Br, I] reactions

“…In organic chemistry the bimolecular nucleophilic substitution (SN2) and the base-induced bimolecular elimination (E2) are elemental reactions and the competitions of these processes have been widely studied both experimentally and theoretically over the past 40 years. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] The traditional Walden-inversion and front-side attack mechanisms of SN2 reactions were described by Ingold and co-workers in the center of the 20th century. 19,20 In a simple SN2 reaction, X − + CH3Y → CH3X + Y − , the Walden-inversion mechanism goes through X − •••CH3Y and XCH3•••Y − minima connected by a central [X•••CH3•••Y] − transition state.…”