Thiazolidine ring opening in penicillin derivatives. Part 2. Enamine formation

Abstract

The alkaline hydrolysis of (3S,5R,6R)-methyl benzylpenicilloate, and the corresponding carboxamide and N-ethylamide, is accompanied by an absorbance increase at 285 nm. This is attributed to a competing elimination reaction across C6–C5 to open the thiazolidine ring and reversibly generate an enamine intermediate. Kinetic analysis and hydrolysis in D₂O do not indicate a significant build-up of this intermediate during hydrolysis of the methyl ester. However, over the pH range 4–11 the rate of thiazolidine ring opening is competitive with hydrolysis of the ester function. The deuterium solvent kinetic isotope effect on the ring closure reaction is 7.5.