Theoretical studies on the gas‐phase nucleophilic substitution reactions of benzyl chlorides with phenoxides and thiophenoxides

Abstract

Gas-phase nucleophilic substitution reactions of Y-benzyl chlorides with X-phenoxide and Xthiophenoxide nucleophiles were investigated theoretically using the PM3 semi-empirical MO method. The LefflerGrunwald rate-equilibrium and Brønsted correlations predict that the degree of bond formation in the transition state (TS) is approximately 45 and 40% on the reaction coordinate for the phenoxides and thiophenoxides, respectively. For a weaker nucleophile, a later TS is obtained with an increased bond making and breaking. The variation of the TS structure with substituents in the nucleophile is thermodynamically controlled and is well correlated by rateequilibrium relationships. In contrast, the TS variation (a tighter TS) with substituent (for a stronger acceptor Y) in the substrate is dependent only on variations of the intrinsic barrier and so cannot be correlated by such thermodynamically based rate-equilibrium relationships. The gas phase r X and r Y values are much greater in magnitude than those in solution. A similar gas-phase theoretical cross-interaction constant, r XY (ca À0.60), is obtained for both phenoxides and thiophenoxides, which is in good agreement with the experimental value (À0.62) for the thiophenoxide reactions in MeOH at 20.0°C. The oxy and sulfur anion bases lead to a similar TS structure, but a lower reactivity for the former is due to a greater endothermicity of the reaction. A relatively wide range variation of the reaction energies, DG°, can be ascribed to the loss of resonance stabilization of anion nucleophiles upon product formation.

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

“…Hence, analysis of the main factors responsible for the ratio between the enthalpy and entropy contribution to the energy barrier for the reaction is of great importance. In this regard, studies on substituent effects in BNRs have been the subject of intense interest . In most cases, substituent effects are quantified by the use of the Hammett or the Hammett‐like substituent constants for aromatic system …”

“…These include S N 2, acyl‐transfer, S N Ar, S N V, and Ad N reactions, etc . Various experimental kinetic and theoretical studies have therefore been devoted to obtain a better understanding of the mechanisms of these processes . Among traditional experimental methods, kinetic isotope effects and linear free energy relationship have most frequently been used to study mechanisms of BNRs, in particular the nature of transition states (TSs) .…”

“…The activation parameters are widely used for characterizing the TS structures . For example, it was found that solvolysis of benzyl‐ and benzhydryl halides follows the S N 2 and S N 1 mechanism, respectively, and S N 2 reactions show more negative values of Δ S ≠ .…”

“…For the effects of substituents on the BNRs, most studies have been done on the influence of structural variations for the single kind of the S N 2, acyl‐transfer, S N Ar reactions, and relatively fewer for the S N V, Ad N , and other BNRs. Therefore, a generalized analysis of the influence of structural variations on activation parameters in S N 2, acyl‐transfer, S N Ar, S N V, and Ad N reactions is of interest.…”

Robust generalized asymptotic regulation against non‐stationary sinusoidal disturbances with uncertain frequencies

“…The results from experimental kinetic and theoretical research on S N 2 reactions in the gas phase5–16 and in the solution17–31 have shown that a full understanding of the chemistry of such processes requires a detailed knowledge of the structural factors with respect to reactivity. Therefore, the effects of structural variations in the substrate, leaving group and nucleophile have received considerable attention 5–31. In this regard, linear free energy relationships (LFER) have been the most useful tool for studying S N 2 reactions in solution 1–4.…”