Alkyl Group Effects on the Rate Constants and Equilibrium Constants for Formation of Cyclic Tetrahedral Intermediates

Article abstract of DOI:10.1021/ja00217a036

2-Hydroxy-2-alkyl-1,3-dioxolanes T are the cyclic intermediates of the degenerate intramolecular ester interchange reactions of ethylene glycol monoalkanoates A, in which alkanoyl groups transfer from one end of ethylene glycol to the other.This study reports equilibrium constants for the cyclization A<=>T to the tetrahedral intermediate stage with 10 alkanoate derivatives.These equiilibrium constants, which when written as / are all large (1 E7-1 E9) in favor of the ring opened form, were obtained as the ratio of rate constants for equilibration occuring with H⁺ catalysis.Rate constants for the ring opening of T were directly measured through a study of kinetics of the hydrolysis of 2-methoxy-2-alkyl-1,3-dioxolane ortho esters.These hydrolysis proceed via T, and under acid conditions the breakdown of this intermediate is rate-limiting.Rate constants in the ring-closing direction were obtained by preparing HOCH2CD2OOCR and, with the use of ¹H NMR spectroscopy, measuring the kinetics of isomerization to an equilibrium mixture with RCOOCH2CD2OH.The reaction under investigation is an intramolecular analogue of H⁺-catalyzed alkanoate ester hydrolysis, whose rate constant define the steric substituent parameter E_s.The ring-closure rate constant for A -> T do show an excellent correlation with E_s.However, the rate constants for ring-opening T -> A and the overall equilibrium constant are badly correlated, showing quite different behavior for series with α and β branching in the alkyl group.Thus, for this system the E_s parameter does not correlate free energy differencies between the acyl derivative and tetrahedral intermediate.It is only the free energy differences between the acyl form and the transition state leading to the intermediate that fit E_s.