Intramolecular aldol condensations: Rate and equilibrium constants

Rate and equilibrium constants have been determined for both the aldol addition and the elimination steps in the intramolecular condensation reactions of 2,5-hexanedione, 2,6-heptanedione, l-phenyl-l,5-hexanedione, and 5-oxohexanal. The overall thermodynamics are similar for cyclization of 2,5-hexanedione and 2,6-heptanedione; conversion of 2,5-hexanedione to the corresponding enone is actually more favorable, but the cyclization of 2,5-hexanedione is 2400 times slower than that of 2,6-heptanedione. As expected on the basis of intermolecular analogs, the addition step is less favorable and slower for 1-phenyl-1,5-hexanedione, and the addition step for 5-oxohexanal is more favorable though similar in rate to that for heptanedione. Detailed analysis of the kinetics and equilibrium for all of these compounds, as well as 2-(2-oxopropyl)benzaldehyde, in terms of Marcus theory, leads to the same intrinsic barriers for the intramolecular reactions as were seen previously for the intermolecular reactions. This means that rate constants for intramolecular aldol reactions should be predictable from the energetics of the reactions and that the effective molarity can be calculated. Methods for estimating thermodynamic quantities for reactants and products of these reactions have been examined.