A Direct Comparison of Reactivity and Mechanism in the Gas Phase and in Solution

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.

Nucleophilic Substitution (SN2): Dependence on Nucleophile, Leaving Group, Central Atom, Substituents, and Solvent

“…The reaction barrier Δ H ≠,ovr at the G2(+) level was found to increase from 2.4 kcal mol −1 for R=methyl, to 4.5 kcal mol −1 for R=ethyl and 6.1 kcal mol −1 for R= iso ‐propyl. Recently, Bierbaum, Westaway, and co‐workers studied the reaction of cyanide with alkyl iodides experimentally and found a decrease in rate constant with increasing alkyl size. Specifically, for CH 3 I, the rate constant was 12.8±0.3 (10 −11 cm 3 s −1 ), which dropped to 2.99±0.02 (10 −11 cm 3 s −1 ) for CH 3 CH 2 I, and to less than 0.1 (10 −11 cm 3 s −1 ) for (CH 3 ) 3 CI .…”

“…Recently, Bierbaum, Westaway, and co‐workers studied the reaction of cyanide with alkyl iodides experimentally and found a decrease in rate constant with increasing alkyl size. Specifically, for CH 3 I, the rate constant was 12.8±0.3 (10 −11 cm 3 s −1 ), which dropped to 2.99±0.02 (10 −11 cm 3 s −1 ) for CH 3 CH 2 I, and to less than 0.1 (10 −11 cm 3 s −1 ) for (CH 3 ) 3 CI . Brauman and co‐workers studied steric effects in ionic S N 2 reactions for Cl − +RCH(CN)Cl and found similarly a decrease in the reaction rate for R=Me (10.0 ⋅ 10 −12 cm 3 s −1 ), R=Et (8.9 ⋅ 10 −12 cm 3 s −1 ), R= iso ‐propyl (2.7 ⋅ 10 −12 cm 3 s −1 ) and R= tert ‐butyl (1.1 ⋅ 10 −12 cm 3 s −1 ).…”

Influence of the leaving group on the dynamics of a gas-phase SN2 reaction

“…Usually, solvent effects are superimposed onto the intrinsic reaction dynamics, which strongly affects the reactivity. However, it is now becoming increasingly clear that on short time scales direct atomistic dynamics of chemical reactions can prevail -at least partially -in a solution phase environment [17][18][19] . By studying S N 2 reactions in the gas phase these intrinsic dynamics, mechanisms and structure-energy relations become accessible.…”

Activation parameter changes as a mechanistic tool in SN2 reactions in solution

“…The significant increase of the energetic barrier by over 63-71 kJ mol -1 for the SN2 reactions of CN -+ CH3I and CN -+ C2H5I occurs in protic and aprotic solvents in comparison with the gas phase. The magnitudes of the electrostatic attraction between the partial negative charges on the nucleophiles in the transition state and the partial positive charge on the α carbon are much larger in the gas phase than in solvent where solvation will reduce these interactions between ions in the transition state [131].…”