A change in rate-determining step in the hydrolysis of cyclic ketals

Abstract

A kinetic study is reported of the hydrolysis of 2-methoxy-2-phenyltetrahydrofuran and 2-ethoxy-2-phenyltetrahydrofuran. At pH > 6 the rate-determining step involves H+-catalyzed formation of the oxocarbocation, this reaction occurring with cleavage of the exocyclic alkoxy group to produce a cyclic cation. Between pH 5 and pH 6 a change-over occurs and at pH < 5, the rate-determining step in product formation is breakdown of the cyclic hemiketal intermediate, 2-hydroxy-2-phenyltetrahydrofuran. The changeover occurs because the H+-catalyzed breakdown of this intermediate is a slower process than the H+-catalyzed oxocarbocation-forming step. Hydroxide ion catalysis makes the hemiketal decomposition faster at higher pH. Analogous cyclic ortho esters (2-alkoxy-1,3-dioxolanes) show this same change in rate-determining step between high pH and low pH, while acyclic acetals, ketals, and ortho esters generally have the oxocarbocation-forming stage rate determining at all acidities. It is concluded that the structural features inherent in the cyclic systems are responsible for the difference. In particular, the oxocarbocation-forming stage involves exocyclic bond cleavage, giving it an entropic advantage over the hemiketal or hemiorthoester breakdown which is endocyclic.