Transition states solvation

Fig. 4.14. Reactant and transition-state solvation in the reaction of ethyl acetate with hydroxide ion. [From P. Haberfield, J. Friedman, and M. F. Pinkson, J. Am. Chem. Soc. 94 71 (1972).]...

Initial state and transition state solvation in inorganic reactions. M. J. Blandamer and J. Burgess, Coord. Chem. Rev., 1980, 31, 93-121 (78). 

Hu and Truhlar have recently reported a modeling transition state solvation at a single-water representation [295]. Recent experimental advances leading to the study of SN2 reactions of gas-phase microsolvated clusters which can advantageously been studied with ab initio electronic theory. These experiments and theoretical studies are quite relevant to chemical reactions in supercritical water. 

Hu, W.-P. and Truhlar, D. G. Modeling transition state solvation at the single-molecule level test of correlated ab initio predictions against experiment for the gas-phase SN2 reaction of microhydrated fluoride with methyl chloride, J.Am.Chem.Soc., 116 (1994), 7797-7800... 

The finding that 2 1 binding of [22] by -CD does not lead to cleavage, whereas it seems to be productive for /3-CD, must relate to subtle differences in the geometries of the 2 1 complexes formed by the two different CDs. More specifically, it probably reflects how tightly the esters [22] are held in the CD cavities and whether the solvent has sufficient access to the reaction centre for transition state solvation (Tee and Du, 1992). 

Although the intermolecular selectivity of the nitration of alkylbenzenes by nitric acid in trifluoroacetic acid is controlled by both electronic and steric factors, it is argued that intramolecular selectivity is controlled by steric effects on transition state solvation. 

The data for acid-catalyzed ester formation in cyclohexanol are doubly interesting. The activation parameters are closely similar to those for the acid-catalyzed hydrolysis of the corresponding ethyl esters. The enthalpy of activation is considerably higher than for esterification in methanol this is probably a result of steric inhibition of solvation, as well as non-bonded compression in the transition state, as suggested by the entropies of activation, which are also significantly higher than with methanol, especially for compounds without ortho substituents which presumably have more transition state solvation to lose. 

Proton abstraction from a model carbon acid, hydroxyacetaldehyde, by formate anion has been examined theoretically for the gas phase and for aqueous solution.152 The reaction shows an early transition state, whereas its enzymatic equivalent has a late transition state. Solvation brings the transition state foiward. The factors that contribute to producing the later transition state in enzymes are discussed. 

The observed decreases in catalysis of the substituted enzymes may be a consequence of increased energy barriers due to the losses of transition state solvation. The effect seems to be mainly on "galactosylation" (k2). This is supported by the results of the nucleophilic competition studies which showed that the addition of methanol to the assay did not result in an increase in the kcat-Furthermore, the kcat values for each enzyme were quite different depending upon which substrate was used. This indicates that "galactosylation" (ka) was rate determining, and shows that this step was affected much more than "degalactosylation" (ks) by the changes in solvation of the planar transition state. 

Since methyl iodide is in general less soluble (has more free energy) in protic than in dipolar aprotie solvents this cannot be the reason for faster reactions in dipolar aprotie vs. protic solvents. The question arises is the large protic-dipolar aprotie solvent effect on rate of reactions such as (27) due to differences in transition state solvation, in reactant anion solvation, or, as suggested by Fig. 1, to some combination of these effects ... 

The two extrathermodynamic assumptions used in Table 9 to derive solvent activity coefficients of anions, lead to different values of y cicHsi-)+ The assumption (i) that caesium cation is similarly solvated in methanol and in DMF, suggests that the large rate difference between reaction (27) in methanol and in DMF is as much due to differences in transition state solvation as to differences in solvation of chloride ion. This is the situation shown qualitatively in Fig. 1. On the other hand, the somewhat smaller rate difference between reaction (27) in formamide and in DMF is due entirely to differences in solvation of chloride ion, if the caesium assumption is applied to formamide and to DMF. 

The difference in rate between reaction in DMF (D), ethanol (E), and nitromethane (N), at ionic strength ca. 0-1m, is accounted for almost entirely by differences in transition state solvation. As discussed in Section Cl, log yf.g. = +1-5 and log yT.s. w 0-0 for (31), so that the rate data in Table 12 leads to log°yMeaS+ °ylr- = - 0-8 through equation (9). Although bromide ion is probably more solvated by ethanol than by DMF, the trimethylsulphonium cation is probably more solvated by DMF than by ethanol (Parker, 1962). 

Because of differences in transition-state solvation (Table 17), the relative ease of displacement of the halide ions and jj-toluenesulphonate from carbon, under otherwise identical conditions, is very dependent on the solvent and the reagent (Coniglio et al., 1966). The behaviour, illustrated in Table 18 for Sfj2 reactions of azide and thiocyanate ions... 

Scheme 2 gives typical half-lives for reactant molecules destined to react." Many encounters do not lead to reaction and only a small fraction of the complexes will have the appropriate transition state solvation in place to form a reaction complex and for reaction to proceed. 

Differential Solvation of Reactants and Transition States. It should always be kept in mind that solvent effects can modify the energy of both the reactants and the transition state. It is the difference in the solvation that is the basis for changes in activation energies and reaction rates. Thus, although it is common to discuss solvent effects solely in terms of reactant solvation or transition state solvation, this is an oversimplification. A case that illustrates this point is the base-promoted hydrolysis of esters by hydroxide ion. 

The reaction is faster in DMSO-water than in ethanol-water. Reactant solvation can be separated from transition state solvation by calorimetric measurement of the heat of solution of the reactants in each solvent system. The data in Figure 3.36 compare the energies of the reactants and TS for ethyl acetate and hydroxide ion reacting in aqueous ethanol versus aqueous DMSO. It can be seen that both the reactants and the TS are more strongly solvated in the ethanol-water medium. The enhancement... 

Two mechanisms have been proposed for this reaction. The first includes a step in which the first methanol is protonated and dehydrated to give a reactive methoxy group attached to the framework, whereas the second involves two methanol molecules undergoing an Sn2 reaction inside the zeolite cage, catalysed by protonation of one of the methanols and with the transition state solvated by the zeolite cage. The conclusion from QM studies (using both cluster and plane wave approaches) is that the reaction proceeds through the latter pathway, in which the zeolite stabilises the transition state. 

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