Content area
Full text
Rates of S^sub N^2 reactions of chloride ion with methyl- and tert-butyl-substituted chloroacetonitrile were measured by using Fourier transform-ion cyclotron resonance spectrometry to follow the isotopic exchange reaction. Barrier heights for these reactions indicate that steric effects in the gas phase are diminished relative to apparent steric effects in solution. We attribute the increased barrier in solution to a solvation effect. Monte Carlo simulations done using statistical perturbation theory confirm that steric hindrance to solvation contributes to S^sub N^2 barriers in solution.
In the S^sub N^2 nucleophilic displacement reaction, a nucleophile, Z (often negatively charged), reacts with a saturated carbon and displaces a leaving group, Y (Scheme 1). Increasing the size of the substituents, R, decreases the rate of the reaction by creating nonbonded interactions (steric effects) that raise the energy of the transition state.
The idea of a steric effect was first proposed by Hofmann (1, 2) 130 years ago, but a quantitative understanding of this effect in the S^sub N^2 reaction remains elusive (3, 4). In solution, there is a dramatic reduction in rates and an increase in activation barriers associated with increasing alkyl substitution at the central carbon atom, regardless of the solvent. Early theoretical attempts using classical models to quantitatively understand the effect of structure on the energetics were mixed (3, 5, 6). Ingold's discussion of steric effects is the benchmark for other studies (3, 7). This early work indicated that steric effects might not account for all of the barrier in solution (8), but only internal effects, such as the change in polar effects with substitution, were proposed to explain the rest of the barrier seen in solution (7). Solvation of transition states was considered equivalent in all cases. However, although structural interference clearly affects chemical behavior (5), we believe that steric effects in ionic reactions in solution are convoluted with solvent effects in a way that has not been explored.
Much of the barrier to the reaction of ions in solution is due to the desolvation of the nucleophile and the greater charge dispersal in the transition state (3, 9, 10). To isolate the role of solvation, however, it is necessary to look at thermoneutral reactions (11), such as isotopic exchange. Interpretation of an activation barrier for exothermic...