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 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.
ABSTRACT
The secondary alpha- and beta-deuterium, the alpha-carbon, the nucleophile carbon, the nucleophile nitrogen, and the chlorine leaving group kinetic isotope effects for the S(N)2 reaction between cyanide ion and ethyl chloride were determined in the very slightly polar solvent THF at 30 degrees C. A comparison of these KIEs with those reported earlier for the same reaction in the polar solvent DMSO shows that the transition state in THF is only slightly tighter with very slightly shorter NC-C(alpha) and C(alpha)-Cl bonds. This minor change in transition state structure does not account for the different transition structures that were earlier suggested by interpreting the experimental KIEs and the gas-phase calculations, respectively. It therefore seems unlikely that the different transition states suggested by the two methods are due to the lack of appropriate solvent modeling in the theoretical calculations. Previously it was predicted that the transition state of S(N)2 reactions where the nucleophile and the leaving group have the same charge would be unaffected by a change in solvent. The experimental KIEs support this view.
ABSTRACT
The secondary alpha-deuterium, the secondary beta-deuterium, the chlorine leaving-group, the nucleophile secondary nitrogen, the nucleophile (12)C/(13)C carbon, and the (11)C/(14)C alpha-carbon kinetic isotope effects (KIEs) and activation parameters have been measured for the S(N)2 reaction between tetrabutylammonium cyanide and ethyl chloride in DMSO at 30 degrees C. Then, thirty-nine readily available different theoretical methods, both including and excluding solvent, were used to calculate the structure of the transition state, the activation energy, and the kinetic isotope effects for the reaction. A comparison of the experimental and theoretical results by using semiempirical, ab initio, and density functional theory methods has shown that the density functional methods are most successful in calculating the experimental isotope effects. With two exceptions, including solvent in the calculation does not improve the fit with the experimental KIEs. Finally, none of the transition states and force constants obtained from the theoretical methods was able to predict all six of the KIEs found by experiment. Moreover, none of the calculated transition structures, which are all early and loose, agree with the late (product-like) transition-state structure suggested by interpreting the experimental KIEs.
ABSTRACT
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.