Determining the Geometries of Transition States by Use of Antihydrophobic Additives in Water

The quantitative effect of cosolvents on the water solubility of hydrophobic substrates can be correlated with the effect on reaction rates to determine the geometries of transition states for Diels−Alder reactions, the benzoin condensation, and alkylations of phenoxide ions and aniline. Some of these reactions have transition states with packing of hydrophobic surfaces and some do not. Methods were devised to sort out the effect of the cosolvents on solvation of hydrophobic surfaces and the effect on solvation of polar groups. The result is a set of geometries for these reactions that is consistent with theory.