Concurrent S_N1 and S_N2 reactions in the benzylation of pyridines

Abstract

The Menschutkin reactions of 3,4‐methylenedioxybenzyl and 3,4‐dimethoxybenzyl bromides and also p‐methoxybenzyl bromide with Y‐substituted pyridines were kinetically studied for a range of amine concentration in acetonitrile. The strongly activated benzyl bromides showed a significant positive intercept in the plot of the pseudo‐first‐order rate constants against the concentrations of nucleophiles, while less activated benzyl bromides did not give such significant intercepts. The rate data for respective substrates were fitted to the equation kobs = k1 + k2[Nu]. The first‐order rate constant, k1, is unaffected by the nature of the nucleophile, whereas the second‐order rate constant, k2, increased with increasing nucleophilicity. This was ascribed to the simultaneous occurrence of SN1 and SN2 reactions without an intermediate mechanism. These results are taken as evidence for the duality of SN1 and SN2 mechanisms in the Menschutkin reaction in the non‐solvolyzing solvent acetonitrile. Copyright © 2001 John Wiley & Sons, Ltd.

Hydrogen-Bonding Catalysis and Inhibition by Simple Solvents in the Stereoselective Kinetic Epoxide-Opening Spirocyclization of Glycal Epoxides to Form Spiroketals

“…21 The resulting Hammett correlation exhibited a negative slope with a ρ value of −1.3, consistent with an S N 2 (or S N 2-like) transition state. 14f,15c,d,18,24 The slope was significantly shallower than that observed for the S N 1 process above ( ρ = −5.1), indicating the smaller electronic influence of the aryl substituents upon this S N 2 reaction.…”

“…Alternatively, an S N 1 mechanism (pathway B) might still afford high stereoselectivity if the C2-alkoxide could sterically and/or electronically block one face of the oxocarbenium ion-pair intermediate. While there is a wealth of literature devoted to describing the influence of nucleophiles, electrophiles, and reaction conditions in promoting S N 1 and S N 2 manifolds in glycosylation 11,12 and solvolysis 12,13 reactions, at benzylic positions 14,15 and at acetals, 16 the majority of these studies have involved inter molecular reactions of relatively simple substrates. Moreover, attempts to distinguish between S N 1 and S N 2 manifolds are complicated by the fact that some of the reactions cited above fall into a gray area along the S N 1–S N 2 continuum and, in some cases, are described as having concurrent, competing reaction manifolds.…”

“…Moreover, attempts to distinguish between S N 1 and S N 2 manifolds are complicated by the fact that some of the reactions cited above fall into a gray area along the S N 1–S N 2 continuum and, in some cases, are described as having concurrent, competing reaction manifolds. 15,17,18 We envisioned that detailed kinetic studies of a series of electronically-tuned glycal epoxide substrates would allow us to distinguish between these two pathways in this intra molecular reaction of these complex substrates.…”

“…To explore this idea further, we first characterized reactions known to proceed by an S N 1 mechanism to serve as a benchmark against which to compare our proposed S N 2 MeOH-catalyzed epoxide-opening spirocyclization. 15,18 …”

Guidelines for O-Glycoside Formation from First Principles

“…In an alternative approach, glycosylation reactions can be considered as taking place via two concurrent competing pathways, namely, the S N 1 and S N 2 pathways, with the operative mix being dependent on a number of factors. Such a scenario has been considered by multiple authors for various types of nucleophilic substitution reaction under nonsolvolytic conditions, − as exemplified by Mayr and co-worker’s study of the substitution reactions of benzyhydryl halides, and their kinetics are typically described by equations of the form of eq , which has been written here for the glycosylation reaction.…”