Do the solvolysis reactions of secondary substrates occur by the SN1 or SN2 mechanism: or something else?

Abstract

Primary and methyl aliphatic halides and tosylates undergo substitution reactions with nucleophiles in one step by the classic S N 2 mechanism, which is characterized by second-order kinetics and inversion of configuration at the reaction center. Tertiary aliphatic halides and tosylates undergo substitution reactions with nucleophiles in two (or more) steps by the classic S N 1 mechanism, which is characterized by first-order kinetics and incomplete inversion of configuration at the reaction center due to the presence of ion pairs. When the nucleophile is also the solvent, the substitution reaction is called a solvolysis, and both the S N 2 and S N 1 reactions now obey first-order kinetics. Schleyer and Bentley have provided solid, but not conclusive, evidence that secondary substrates undergo solvolysis by a merged mechanism, one that blends characteristics of both the S N 2 and S N 1 mechanisms. The following paper presents the history of their sustained pursuit of a merged mechanism and subsequent rebuttals to this claim. Several issues related to the philosophy and sociology of science are also discussed.

Exploring borderline SN1–SN2 mechanisms: the role of explicit solvation protocols in the DFT investigation of isopropyl chloride

“…Along the continuum between these two mechanisms, the S N 2 may gradually shift toward S N 1 as the transition state develops a carbocation character. 3–6…”

“…3 Some studies describe the solvolysis reactions of secondary substrates following a merged mechanism, exhibiting both S N 1 and S N 2 characteristics. [5][6][7][8] This process oen involves active nucleophilic solvent assistance (NSA) in the rate-determining step (sometimes referred as S N 3). 9,10 While extensive efforts have been devoted to unraveling the intricate effects of solvation in chemical processes, accounting for precise solvent effects into quantum simulations of chemical reactions remains a substantial challenge.…”

“…Along the continuum between these two mechanisms, the S N 2 may gradually shi toward S N 1 as the transition state develops a carbocation character. [3][4][5][6] A key factor inuencing the gradual transition from S N 1 to S N 2 mechanisms is the solvent activity. 3 Some studies describe the solvolysis reactions of secondary substrates following a merged mechanism, exhibiting both S N 1 and S N 2 characteristics.…”

“…This phenomenon is recognized as a merged or borderline mechanism, displaying characteristics of both S N 1 and S N 2 reactions. [5][6][7][8] Nucleophilic substitution reactions, such as hydrolysis, play pivotal roles in numerous biochemical and synthetic transformations. [27][28][29] Our primary goal is to evaluate the nature of borderline mechanisms in the hydrolysis reaction and investigate how the number (n) and the conguration of explicit water molecules inuence the overall energy prole and the nature of the transition state structures.…”