Vibrational Activation. 2.1 Acceleration of Bond-Making Reactions by Solvent Viscosity as a Model for Enzymic Catalysis. The Claisen Rearrangement and the Diels-Alder Reaction

Article abstract of DOI:10.1021/jo00323a037

The vibrational activation theory holds that enzymes catalyze reactions in part by simply immobilizing the reactants.Typical bond-making reactions should then go faster at high viscosities.This prediction has now been verified for two different reactions.At 138 deg C the Claisen rearrangement of phenyl allyl ether goes at relative rates of 1.00, 0.98, 1.13, and 1.36 in n-octane, isooctane, n-octacosane, and Nujol, whose relative viscosities at 100 deg C are 1.00, 0.94, 4.92, and 11.8, respectively.The relationship is linear with slope 0.041.Addition of polyethylene to the Nujol raises the relative viscosity to 48.5 and the relative rate to 1.70.The intramolecular Diels-Alder cyclization of N-propargyl-9-anthroamide at 100 deg C goes at relative rates 1.00, 1.16, 1.25, and 1.38 in mono-, di-, tri- and tetraglyme, whose relative viscosities at 100 deg C are 1.00, 1.28, 1.54, and 1.99, respectively.The relationship is again linear, with slope 0.37.In addition, the following examples from the literature are analyzed in terms of viscosity-induced accelerations: the dimerization of cyclopentadiene, pressure-accelerated reactions where /-ΔV(excit.)/ > /-ΔV/ and liquid/gas rate ratios are > 1.A test of the theory that the liquid/gas phenomenon stems from hyperpolarizability of the transition state was made by measuring Claisen relative rates in five solvents of widely varying refractive indices.No relationship between rate and solvent polarizability was found.