Effects of substituents on activation parameters in S_N2 reactions at aliphatic carbon in solution

Abstract

Changes of the activation parameters in aliphatic SN2 reactions with anionic and neutral nucleophiles in various solvents, ΔH≠ and ΔS≠, were correlated with σ constants of the substituents. The resultant δΔH≠ and δΔS≠ reaction constants are linearly related for variations of substituents at the substrate, leaving group and nucleophile. Correlations of δΔH≠ versus δΔS≠ allow the estimation of the contribution of changes of the internal enthalpy, δΔH ≠int, to the enthalpy reaction constant, δΔH≠, which gives a single linear dependence on the Hammett ρ reaction constants. The deviations from the dependence of δΔH ≠int versus ρ can be interpreted in terms of changes in the transition state structure in SN2 reactions. The results obtained show that the substituent effects on the charge development in the transition state are governed by the magnitude of δΔH ≠int. Copyright © 2009 John Wiley & Sons, Ltd.

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

“…The latter have a large positive value of δΔS ≠ . Obviously, the arrangement of lines I -III and entries 14 and 40 on Figure 1 reflects the reactivity order of SN2 reactions with decreasing the values of δΔН ≠ [24,27]. The plots of δΔН ≠ versus δΔS ≠ for SN2 reactions with the substituents R in the leaving group YCH2ZC6H4R (I), nonleaving group RC6H4ZCH2X (II) and nucleophile RC6H4Z -(RC6H4ZH) (III); values of δΔН ≠ and δΔS ≠ are taken from Table 1; line I, δΔН ≠ = (-8.0 ± 0.3) + (0.29 ± 0.03) δΔS ≠ , r = 0.950, s = 1.1, n = 13; line II, δΔН ≠ = (-1.5 ± 1.2) + (0.38 ± 0.03) δΔS ≠ , r = 0.973, s = 4.1, n = 11; line III, δΔН ≠ = (11.4 ± 0.9) + (0.37 ± 0.02) δΔS ≠ , r = 0.990, s = 3.32, n = 12; the compensation equations for lines I -III are tested at the 92%, 95.7% and 97.6% confidence level, respectively [43]; the identity of the numbers is the entry number in Table 1.…”

“…Variations of the activation parameters δΔН ≠ and δΔS ≠ in the SN2 reactions with neutral and charged nucleophiles in various solvents in Table 1 reflect the sensitivity of activation parameters to substituent nature in the leaving groups, nucleophiles and nonleaving groups and strongly depend on solvation of reactants and TSs (Scheme 1) [24][25][26][27][37][38][39][40]. Negative values of δΔН ≠ and δΔS ≠ indicate enhanced solvation of the corresponding TS-1 upon introduction of electronwithdrawing substituents R (entries 15-17, 25-28, 34-36 in Table 1).…”

“…There are three compensation relationships between δΔН ≠ and δΔS ≠ for SN2 reactions at saturated carbon atom including the changes of the substituents R in the leaving group (entries 1-13 in Table 1), nonleaving group (entries [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and nucleophiles (entries 30-42) ( Figure 1).…”

“…There is the one deviation from line I (Figure 1) depicting the dependence of δΔН ≠ versus δΔS ≠ for the reactions of substituted N-methylpyridinium salts with iodide ion (entry 14 in Table 1). These reactions are characterized by very low rate constants (k2 = 1×10 -12 -1×10 -9 dm 3 •mol -1 •s -1 ) [50] and by a large negative value of δΔН ≠ [24,27]. An analogous deviation from the dependence of δΔН ≠ versus δΔS ≠ for the line III ( Figure 1) is connected with a large positive value of δΔS ≠ for the reactions of N-substituted anilines with benzyl bromide in methanol (entry 40 in Table 1).…”

“…Among traditional experimental methods, kinetic isotope effects [12][13][14][15] and linear free energy relationships (LFER) [16][17][18][19] have most frequently been used to study mechanisms of BNRs, in particular the nature of transition states (TSs) [20][21][22]. Besides, the influence of the variations of substituents in reactants on activation parameters in BNRs including SN2 reactions was demonstrated [23][24][25][26][27].…”