Reactions between Neutral, Apolar Molecules

In any solution reaction, cavities in the solvent must be created to accommodate reactants, activated complex, and products. Thus, the ease with which solvent molecules can be separated from each other to form these cavities is an important factor in solute solubility cf. Section 2.1). Furthermore, because solubility and reactivity are often related phenomena, the intermolecular forces between solvent molecules must also influence rates of reaction. The overall attractive forces between solvent molecules gives the solvent as a whole a cohesion which must be overcome before a cavity is created. The degree of cohesion may be estimated using the surface tension, but a more reliable estimate is obtained by considering the energy necessary to separate the solvent molecules. This is known as the cohesive pressure c (also called cohesive energy density) [228- 

The cohesive pressure is defined as the energy of vapourization, Ally, per unit molar volume, Fm, as shown in Eq. (5-76) cf. also Eq. (3-5) in Section 3.2. 

Values of c are calculated from experimentally determined enthalpies (heats) of vapourization of the solvent to a gas of zero pressure, AH, at a temperature T, as well as from the molecular mass M, the density of the solvent g, and the gas constant, R. The cohesive pressure characterizes the amount of energy needed to separate molecules of a Hquid and is therefore a measure of the attractive forces between solvent molecules. The cohesive pressure c is related to the internal pressure n, because cohesion is related to the pressure within a liquid cf. Eq. (3-6) in Section 3.2 for the precise definition of n.  

In mixtures which are regular solutions the mutual solubility of the components depends on the cohesive pressure, hence Hildebrand termed the square root of c the solubility parameter 8, according to Eq. (5-77) cf. also Eq. (2-1) in Section 2.1 [228, 229, 231, 238]. 

A good solvent for a certain nonelectrolyte solute should have a 8 value close to that of the solute [cf Section A.l). Extensive compilations of 8 values are given in references [231, 238] a selection ofd values for various organic solvents is given in Table 3-3 in Section 3.2. 

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In summary, the acceleration in water of reactions between neutral molecules arises from an enforced hydrophobic effect (especially when apolar reactants are involved), and a charge development in transition states in particular when one of the reactants is a hydrogen donor or acceptor. In both cases a negative volume of activation is expected. The two contributions (hydrophobic effects and polarity) could be active in the same reaction, which means a greater destabilization of the hydrophobic reactants in the initial state than in the transition state, and a greater stabilization of a more polar transition state. 

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