Quantitative antihydrophobic effects in water and the geometries of transition states

3 Quantitative antihydrophobic effects in water and the geometries of transition states 

Throughout this account we have been using antihydrophobic additives such as guanidinium cation or alcohols to show that there was some hydrophobic overlap in the transition states of various reactions. We realized that this could be made quantitative - the magnitude of the effect of the antihydrophobic additive on a rate could be related to the amount of hydrophobic surface that becomes hidden from the water in the transition state. This work was reviewed recently. 

In our first study, we examined the effect of added alcohols on the solubility of benzalde-hyde in water and on the rate of the benzoin condensation in water. We saw — in a plot with 15 points - that there was a good parallel between the log of the solubility and the log of the rate constant effect (increased solubility and decreased rate with added alcohols in water). Since the effect of added alcohols on the solubility ofbenzaldehyde simply reflects the antihydrophobic role of the additives, this must also be true of the rate effects. That is, apparently there was no extra effect relating to solvation of charges in the rate changes with additives they simply reflected the fact that the transition state for the benzoin condensation -under these conditions the transition state occurs during the addition of the cyanohydrin anion to the aldehyde - is less stabilized by additives than is the starting material. Some 

From the slope of the plot, we could see that about 40% of one face of each phenyl group is inaccessible to water solvent in the transition state. We will return to such quantitative calculations later. In that paper, we also examined the effect of antihydrophobic additives on the rates of some displacement reactions, such as the reaction of N-methylaniline with the sodium salt of p-carboxybenzyl chloride (the carboxylate group was added to achieve water solubility). We must return later to such displacement reactions to see how much the additives affect the solvation of charges in these cases. 

In the second early paper in this series, we examined the quantitative effect of antihy-drophobic additives on some Diels-Alder reactions. We plotted the effect of three different 

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