The α‑Effect in Gas-Phase S N 2 Reactions of Microsolvated Anions: Methanol as a Solvent Ditte L. Thomsen, †,‡ Jennifer N. Reece, ‡ Charles M. Nichols, ‡ Steen Hammerum, † and Veronica M. Bierbaum* ,‡ † Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark ‡ Department of Chemistry and Biochemistry, University of Colorado, 215 UCB, Boulder, Colorado 80309, United States ABSTRACT: The α-effect, an enhanced reactivity of nucleophiles with a lone-pair adjacent to the reaction center, has been studied in solution for several decades. The gas- phase α-effect has recently been documented in studies of S N 2 reactions as well as in competing reactions for both bare and microhydrated anions. In the present work we extend our studies of the significance of microsolvation on the α-effect, employing methanol as the solvent, in the expectation that the greater stability of the methanol cluster relative to the water cluster will lower the reactivity and thereby allow studies over a wider efficiency range. We compare the gas-phase reactivity of the microsolvated α- nucleophile HOO - (CH 3 OH) to that of microsolvated normal alkoxy nucleophiles, RO - (CH 3 OH) in reactions with CH 3 Cl and CH 3 Br. The results reveal enhanced reactivity of HOO - (CH 3 OH) toward both methyl halides relative to the normal nucleophiles, and clearly demonstrate the presence of an α-effect for the microsolvated α-nucleophile. The highly exothermic reactions with methyl bromide result in a smaller Brønsted β nuc value than observed for methyl chloride, and the α-effect in turn influences the reactions with methyl chloride more than with methyl bromide. Computational investigations reveal that reactions with methyl bromide proceed through earlier transition states with less advanced bond formation compared to the related reactions of methyl chloride. In addition, solvent interactions for HOO - are quite different from those with the normal nucleophiles at the transition state, indicating that differential solvation may well contribute to the α-effect. The greater thermodynamic and kinetic stability of the anion-methanol clusters relative to the anion-water clusters accounts well for the differences in the influence of solvation with the two protic polar solvents. ■ INTRODUCTION Nucleophiles that possess a lone pair of electrons adjacent to the attacking center are known as α-nucleophiles. The term covers both ionic nucleophiles such as the hydrogen peroxide and hypochlorite anions, and neutral nucleophiles such as hydrazine and hydroxylamine. In solution, α-nucleophiles are known to display enhanced reactivity relative to normal nucleophiles of similar basicity, and the term α-effect 1 has been used to describe this modified reactivity which can be assessed with Brønsted type correlations. The effect has been observed in several different types of reactions including S N 2 reactions. 2-7 The magnitude of the α-effect for reactions with specific substrates can be determined as the ratio of rate constants for the reactions of an α-nucleophile (k α ) and a normal nucleophile (k normal ) of similar basicity. 8 α-Effects have been reported for numerous reactions in such diverse solvents as H 2 O, dimethylsulfoxide (DMSO), and CH 3 CN. 9 This has led to an active controversy about whether the α-effect is controlled by inherent properties of the α-nucleophile or by external solvent effects. Gas-phase studies provide a vital means to explore the intrinsic nature of the α-effect. Recently, the presence of an intrinsic component of the α-effect in S N 2 reactions was demonstrated by comparing the gas-phase reactivity of HOO - to that of the normal nucleophiles HO - , CH 3 O - ,C 2 H 5 O - , and i-C 3 H 7 O - in reactions with methyl fluoride, anisole, and fluoroanisole. 10 Furthermore, a gas-phase α-effect has been shown to affect reactions of HOO - with methyl formate 11,12 and dimethyl methylphosphonate, 13 and theoretical studies support the premise that the α-effect has a component that can be attributed to intrinsic properties of the nucleophile. 14-19 The influence of solvent on the α-effect still remains intriguing. It is possible in gas-phase ion-molecule studies to investigate reactions in an environment with a controlled number of solvent molecules, known as microsolvation. In a recent paper 20 describing S N 2 reactions of microsolvated anions (HOO - , HO - , CH 3 O - ,C 2 H 5 O - , and i-C 3 H 7 O - ) with methyl chloride, we demonstrated how associating the anions with a single water molecule uncovered the presence of an α-effect otherwise not apparent for the reactions of the unsolvated anions. 21 In the absence of solvation large reaction efficiencies mask the α-effect, 22 but the association of a single water Special Issue: A. W. Castleman, Jr. Festschrift Received: August 1, 2013 Revised: October 9, 2013 Published: October 11, 2013 Article pubs.acs.org/JPCA © 2013 American Chemical Society 8060 dx.doi.org/10.1021/jp407698a | J. Phys. Chem. A 2014, 118, 8060-8066