Stabilisation of the thromboxane ring system by electron-withdrawing substituents. Mechanism and reactivity in the hydrolysis of alkyl and aryl oxetane acetals

Abstract

Rates of acid-catalysed hydrolysis are reported as a function of pH for eleven oxetane acetals (6) in 20% dioxane–water. The introduction of fluorine atoms into the 2-alkoxy group results in a 10³–10⁴-fold kinetic stabilisation, and the system is also stabilised by 2-aryl substituents. The pH–rate profiles for the two most reactive compounds (3b) and (12b) show that at low pH the reaction involves rapid conversion into the intermediate hemiacetal, followed by its rate-determining decomposition. For these compounds at pH > 6, and for all other oxetane acetals studied, the ring-opening step is rate determining. No general acid catalysis is apparent.