Towards mechanisms of bimolecular nucleophilic reactions in solution—probing the variation of the activation parameters in the reactions of aromatic compounds

Abstract

Variation of the activation parameters in the SN2, acyl‐transfer, SNAr, SNV, and AdN reactions offers a uniquely useful probe for the mechanistic features of these reactions in solution. New approach uses the substituent effects on the aromatic ring to the variation of the activation parameters, ΔH≠ and ΔS≠, in the above reactions in the frameworks of the Hammett‐like equations in order to evaluate the resultant δΔH≠ and δΔS≠ reaction constants. Compensation relationships of δΔH≠ versus δΔS≠ allow one to estimate the contribution of changes of the internal enthalpy, δΔH≠int, to the enthalpy reaction constant, δΔH≠, that is inherent to bimolecular nucleophilic reactions and gives a single linear dependence on the Hammett ρ reaction constants for these reactions. The deviations from dependence of δΔH≠int versus ρ serve as useful points of interpretation of changes of the transition state structure or reaction mechanism. The results obtained show that the substituent effects in the substrates, nucleophiles, and leaving groups on the mechanistic features in bimolecular nucleophilic reactions are governed by the magnitude of δΔH≠int. Copyright © 2011 John Wiley & Sons, Ltd.

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

“…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).…”

“…The lines II and III from Figure 1 combine a relatively fast reactions [50,[53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] and the compensation relationships for these lines are tested at a confidence level of >95% [27,43]. The slopes of the lines II and III correspond to compensation temperatures Tcomp equaling 380 and 370 K, respectively.…”

“…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].…”