The rates of intramolecular condensation of a series of monoesters of dicarboxylic acids havebeen shown to be highly dependent on the nature of the intervening groups. To underst
and the origin ofthis effect, we estimated
SNAC,S, the entropy difference between the ensemble of accessible ground stateconformers
and a single ground state conformer having transition-state-like geometry.
SNAC,S differs fromthe activation entropy for the reaction by
STS,NAC, the difference in vibrational entropy between the selectedground state conformer
and the transition state. The estimated values of
SNAC,S correlate well (
R2 = 0.96
and 0.73 using dielectric constant values of 80
and 1, respectively) with experimentally determined reactionrate constants. Normal-mode analysis performed on minimized ground state conformations of each moleculesuggests that the change in vibrational entropy makes only a small contribution to the total activation entropy.These results indicate that the conformational entropy difference between the transition
and the groundstates contributes significantly to the free energy of activation.