Oxidative cleavage of β-​lactam ring of cephalosporins with chloramine T in alkaline medium: a kinetic, mechanistic, and reactivity study

摘要

Cephalosporins are β-​lactam antibiotics, and the important drugs of this group are cephalexin, cefadroxil and cephradine. In the present research, the kinetics and mechanism of oxidn. of cephalexin (CEX)​, cefadroxil (CFL)​, and cephradine (CPD) with chloramine-​T (CAT) in alk. medium were investigated at 301 K. All the three oxidn. reactions follow identical kinetics with a first-​order dependence each on [CAT]​o and [substrate]​o. The reaction is catalyzed by hydroxide ions, and the order is found to be fractional. The dielec. effect is neg. Proton inventory studies in H2O-​D2O mixts. with CEX as a probe have been made. Activation parameters and reaction consts. have been evaluated. Oxidn. products were identified by mass spectral anal. An isokinetic relation was obsd. with β = 378 K, indicating that enthalpy factors control the rate. The rate increases in the following order: CPD > CFL > CEX. The proposed mechanism and the derived rate law are consistent with the obsd. kinetics.