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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 alpha- and beta-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 alpha 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 approximately 1% of the gas phase reaction is ascribed to an elimination process.

The effect of inert salts on the structure of the transition state has been determined by measuring the secondary alpha deuterium and the chlorine leaving group kinetic isotope effects for the S(N)2 reaction between n-butyl chloride and thiophenoxide ion in both methanol and DMSO. The smaller secondary alpha deuterium isotope effects and very slightly larger chlorine isotope effects found in both solvents when the inert salt is present suggests that the S(N)2 transition state is tighter and more product-like, with a shorter S-C(alpha) and very a slightly longer C(alpha)-Cl bond when the added salt is present. The salt effect on the reaction in methanol where the reacting nucleophile is the solvent-separated ion-pair complex is much greater than the salt effect on the reaction in DMSO where the reacting nucleophile is the free ion. This greater change in transition-state structure found when the inert salt is present in methanol is consistent with the solvation rule for S(N)2 reactions. The greater change in the S-C(alpha) bond is predicted by the bond strength hypothesis. A rationale for the changes found in transition-state structure when the inert salt is present is suggested for both the free-ion and the ion-pair reactions.

The primary hydrogen−deuterium incoming nucleophile KIEs for the SN2 reactions between para-substituted benzyl chlorides and borohydride ion in DMSO at 30.000 ± 0.002 °C are small (≤1.14) and insensitive to a change in substituent at the α-carbon. The small Hammett ρ (0.51) and ρr (−0.52) values found when the para substituent on the benzene ring of the substrate is altered indicate there is very little charge on the α-carbon in the transition state. The large, constant secondary α-deuterium KIEs of 1.089 ± 0.002 and the large chlorine leaving group KIEs of 1.0076, 1.0074, and 1.0078 found for the p-methyl-, the p-hydrogen-, and the p-chlorobenzyl chloride reactions suggest that the transition states for these reactions are unsymmetric with short H−Cα and long B−Η and Cα−Cl bonds. The decrease in the chlorine leaving group KIE from 1.0076 ± 0.0003 for the p-methylbenzyl chloride reaction to 1.0036 ± 0.0003 for the p-nitrobenzyl chloride reaction indicates the Cα−Cl bond shortens markedly when a strongly e...

Two methods have been used to measure the chlorine leaving group kinetic isotope effect for the S(N)2 reduction of benzyl chloride to toluene by sodium borohydride in DMSO at 30.000 °C. The reaction was monitored by titrating the unreacted borohydride ion. One method involved determining the chlorine isotope effect using the classical IRMS method, which requires the conversion of the chloride ions into gaseous methyl chloride that is analyzed in an isotope ratio mass spectrometric analyses (Hill, J. W.; Fry, A. J. Am. Chem. Soc. 1962, 84, 2763. Taylor, J. W.; Grimsrud, E. P. Anal. Chem. 1969, 41, 805.). Two different measurements using this method yielded isotope effects of k(35)/k(37) = 1.007 19 ± 0.000 19 and 1.007 64 ± 0.000 19. The second method was a new technique where the ratio of the chlorine isotopes was obtained by fast atom bombardment mass spectrometry on the silver chloride recovered from the reaction, i.e., from the first step in the classical procedure. Therefore, the new method is much simpler and avoids the time-consuming preparation, purification, and recovery of the gaseous methyl chloride. Although the experimental error is larger (k(35)/k(37) = 1.008 03 ± 0.00 10 and 1.008 02 ± 0.000 65) when the new technique is used to analyze the silver chloride samples from the same set of experiments that were used to measure the isotope effect by the classical method, the chlorine isotope effect found by the two methods is identical within experimental error. This large chlorine kinetic isotope effect indicates there is considerable C(α)-Cl bond rupture in the S(N)2 transition state.

The secondary α deuterium and heavy atom kinetic isotope effects found for two different SN2 reactions suggest that the magnitude of secondary α deuterium kinetic isotope effects can be determined by the length of only the shorter (stronger) reacting bond in an unsymmetrical SN2 transition state rather than by the usual nucleophile−leaving group distance. Although this means the interpretation of these isotope effects is more complex than has been recognized, the results suggest that they can be used to determine whether an SN2 transition state is symmetrical or unsymmetrical.

A large incoming group 11C/14C kinetic isotope effect of 1.0104 ± 0.0023 has been measured for the SN2 reaction between benzyl chloride and labeled cyanide ion in 20% aqueous DMSO at 30.00 °C. These large incoming group kinetic isotope effects have also been measured for the SN2 reactions of other para-substituted benzyl chlorides with cyanide ion. A combination of the incoming group 11C/14C and chlorine (Hill J. W.; Fry, A., J. Am. Chem. Soc. 1962, 84, 2763) leaving group kinetic isotope effects have been used to model the SN2 transition states for these reactions. Adding a more electron-withdrawing para substituent to the substrate does not affect the stronger N⋮C- - -Cα reacting bond significantly but shortens the weaker Cα- - -Cl reacting bond markedly.