Rate-Limiting Deprotonation in Tetrahedral Intermediate Breakdown

Article abstract of DOI:10.1021/ja00336a044

A kinetic study in acetate and formate buffers is reported of the breakdown to β-hydroxyethyl benzoate of the hemiorthoester-type tetrahedral intermediate 2-phenyl-2-hydroxy-1,3-dioxolane.This species is generated as a transient intermediate in acid solutions in the hydrolysis of the amide acetals 2-phenyl-2-(dimethylamino)-1,3-dioxolane and 2-phenyl-2-(1-imidazolyl)-1,3-dioxolane.Plots of observed rate constant vs. buffer concentration exhibit pronounced curvature in dilute buffers suggestive of a change in rate-limiting step with changing buffer concentration.A mechanism is proposed involving deprotonation of the hydroxy group of the hemiorthoester to produce a highly reactive anion.In the absence of buffer and in very dilute buffers the deprotonation step is rate limiting, the anionic hemiorthoester going on to product at a rate faster than it is reprotonated.In more concentrated buffers the deprotonation step becomes reversible because of the availability of the acid component of the buffer for the reprotonation.A kinetic analysis is presented, providing a rate constant of approximately 5 x 10⁷ s^-1 for breakdown of the anionic hemiorthoester.This intermediate is comparable to that which would be encountered during the hydrolysis of a benzoate ester, and some consequences of the large reactivity are discussed.This is suggested to be a contributing factor behind the small amount of carbonyl (18)O exchange observed during the base hydrolysis of esters.It is also pointed out that with leaving groups significantly better than alcoxide, the lifetime may become so short that the tetrahedral intermediate anion could not exist.In this case an acyl transfer reaction proceeding via this anion would have to be regarded as being concerted with the anion as a transition state, not an intermediate.