On the mechanism of dehydration of a beta-hydroxycyclopentanone analogue of prostaglandin E1

Abstract

The dehydration of the beta-hydroxycyclopentanone, 11,16-dihydroxy-16-methyl-9-oxo-13-trans-protenoic acid methyl ester, an analogue of prostaglandin E1, proceeds with acid catalysis (pH less than 3), by uncatalyzed routes (pH congruent to 4 and congruent to 7), and with base catalysis (pH congruent to 5-6 and greater than 8). Deuterium from the solvent is not introduced alpha to the reactant keto function at 60% reaction at pH congruent to 1, but approximately 30% exchange has occurred at pH congruent to 5, 50% at pH congruent to 7, and 80% at pH congruent to 9. The data are consistent with a mechanism in which the substrate is initially enolized with catalysis by acid, base, and water to a 1,3-enediol, which looses water with catalysis by acid, base, and water. The first stage is rate determining in very acidic solution, while the second stage assumes the limitation of rate to an ever greater degree as the solution becomes more basic.