A Direct Comparison of Reactivity and Mechanism in the Gas Phase and in Solution John M. Garver, † Yao-ren Fang, ‡ Nicole Eyet, †,§ Stephanie M. Villano, † Veronica M. Bierbaum,* ,† and Kenneth Charles Westaway* ,‡ Department of Chemistry and Biochemistry, UniVersity of Colorado, Boulder, Colorado 80309, and Department of Chemistry and Biochemistry, Laurentian UniVersity, Sudbury Ontario, P3E 2C6, Canada Received November 5, 2009; E-mail: veronica.bierbaum@colorado.edu; kwestaway@laurentian.ca Abstract: Direct comparisons of the reactivity and mechanistic pathways for anionic systems in the gas phase and in solution are presented. Rate constants and kinetic isotope effects for the reactions of methyl, ethyl, isopropyl, and tert-butyl iodide with cyanide ion in the gas phase, as well as for the reactions of methyl and ethyl iodide with cyanide ion in several solvents, are reported. In addition to measuring the perdeutero kinetic isotope effect (KIE) for each reaction, the secondary R- and -deuterium KIEs were determined for the ethyl iodide reaction. Comparisons of experimental results with computational transition states, KIEs, and branching fractions are explored to determine how solvent affects these reactions. The KIEs show that the transition state does not change significantly when the solvent is changed from dimethyl sulfoxide/methanol (a protic solvent) to dimethyl sulfoxide (a strongly polar aprotic solvent) to tetrahydrofuran (a slightly polar aprotic solvent) in the ethyl iodide-cyanide ion S N 2 reaction in solution, as the “Solvation Rule for S N 2 Reactions” predicts. However, the Solvation Rule fails the ultimate test of predicting gas phase results, where significantly smaller (more inverse) KIEs indicate the existence of a tighter transition state. This result is primarily attributed to the greater electrostatic forces between the partial negative charges on the iodide and cyanide ions and the partial positive charge on the R carbon in the gas phase transition state. Nevertheless, in evaluating the competition between S N 2 and E2 processes, the mechanistic results for the solution and gas phase reactions are strikingly similar. The reaction of cyanide ion with ethyl iodide occurs exclusively by an S N 2 mechanism in solution and primarily by an S N 2 mechanism in the gas phase; only ∼1% of the gas phase reaction is ascribed to an elimination process. Introduction The influence of solvent on reactions has intrigued chemists for many years. Ions in the gas phase often react differently than the same ions in solution, where coordinating solvent molecules stabilize charges. These effects are evident in the large differences between reaction rate constants of identical gas and condensed phase reactions, 1,2 in the reversal of ordering of acidities and basicities in solution versus the gas phase, 3,4 as well as in the enhanced nucleophilicity of polarizable nucleo- philes in solution versus the gas phase. 5 While gas phase studies allow one to probe the intrinsic reactivity of a molecule, a comparison of these results to solution allows one to directly probe the role of the solvent. For example, Figure 1 shows a potential energy diagram for an S N 2 reaction in the gas phase (curve a), in an aprotic solvent (curve b), and in a protic solvent (curve c). In the gas phase, the ion and neutral molecule are attracted by ion-dipole and ion-induced-dipole forces, resulting in the formation of an encounter complex. Because the energy † University of Colorado. ‡ Laurentian University. § Current address: Department of Chemistry, Saint Anselm College, 100 Saint Anselm Dr. #1760, Manchester, NH 03102. (1) Bohme, D. K.; Mackay, G. I. J. Am. Chem. Soc. 1981, 103, 978–979. (2) Bohme, D. K.; Rakshit, A. B.; Mackay, G. L. J. Am. Chem. Soc. 1982, 104, 1100–1101. (3) Brauman, J. I.; Blair, L. K. J. Am. Chem. Soc. 1970, 92, 5986–5987. (4) Taft, R. W. Prog. Phys. Org. Chem. 1983, 14, 247–350. (5) Olmstead, W. N.; Brauman, J. I. J. Am. Chem. Soc. 1977, 99, 4219– 4228. Figure 1. Potential energy diagram of a generic S N 2 reaction in the gas phase (curve a), in an aprotic solvent (curve b), and in a protic solvent (curve c). Published on Web 02/26/2010 10.1021/ja909399u  2010 American Chemical Society 3808 9 J. AM. CHEM. SOC. 2010, 132, 3808–3814