THIAZOLIDINE RING-OPENING IN PENICILLIN DERIVATIVES .2. ENAMINE FORMATION

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.