Mechanism of bimolecular nucleophilic substitution. Part 9. Stereochemical course of ortho-alkylation of phenoxide ion with optically active alkyl halides under SN2 reaction conditions

Abstract

The rate, product distribution, and stereochemical course for reactions of sodium phenoxide with 1-phenylethyl chloride and butyl bromide, respectively in acetone and in 2,2,2-trifluoroethanol at 100.0°, have been investigated as a function of phenoxide concentration. Alkylation with both halides obeys second-order kinetics. The rate constants increase at lower phenoxide concentrations, indicating that dissociated phenoxide ion has higher nucleophilic reactivity than the ion-pair or higher aggregates. The results of product analyses for the reactions at various phenoxide concentrations reveal that the dissociated phenoxide ion does not afford the C- but solely the O-alkyl derivative, where the ion-pair can give rise to both C- and O-alkyl derivatives. Alkylations with optically active 1-phenylethyl chloride and [1-²H]butyl bromide show that O- and para-alkylation (one of the possible C-alkylations) proceed with complete inversion of configuration, whereas the ortho-alkyl derivatives possess inverted configurations but accompanied by considerable (30–70%) racemization, despite their formation under S_N2 reaction conditions. This is explained by ortho-alkylation proceeding partly by front-side attack of the phenoxide ion-pair, probably via a cyclic six-membered transition state. The possibility of a correlation between the mechanism of this sterically unexpected bimolecular ortho-alkylation and Sneen's ion-pair mechanism, proposed for bimolecular S_N reactions, is discussed.