La3+-Catalyzed Methanolysis of N-Aryl-(beta)-lactams and Nitrocefin

The kinetics of the La3+-catalyzed methanolysis of N-phenyl-(beta)-lactam (2) and N-p-nitrophenyl-(beta)-lactam (3) as well as that of nitrocefin (1) were studied at 25 °C under buffered conditions. In the case of 2 and 3, the observed second-order rate constants (k2obs) for catalysis plateau at ~spH 7.5-7.8, reaching values of 1 × 10^-2 and 35 × 10^-2 M^-1 s^-1 respectively. Potentiometric titrations of solutions of 2 × 10^-3 M La(OTf)3 were analyzed in terms of a dimer model (La3+2(-OCH3)n), where the number of methoxides varies from 1 to 5. The species responsible for catalysis in the pH range investigated contain 1-3 methoxides, the one having the highest catalytic activity being La3+2(-OCH3)2, which comprises 80% of the total La3+ forms present at its pH maximum of 8.9. The catalysis afforded by the La3+ dimers at a neutral spH is impressive relative to the methoxide reactions: at spH 8.4 a 1 mM solution of catalyst (generated from 2 mM La(OTf)3) accelerated the methanolysis of 2 by ~2 × 10^7-fold and 3 by ~5 × 10^5-fold. As a function of metal ion concentration, the La3+-catalyzed methanolysis of 1 proceeds by pathways involving first one bound metal ion and then a second La3+ leading to a plateau in the kobs vs [La3+]total plots at all pH values. The kmaxobs pseudo-first-order rate constants at the plateaus, representing the spontaneous methanolysis of La3+2(1-) forms, has a linear dependence on [-OCH3] (slope = 0.84 ± 0.05 if all pH values are used and 1.02 ± 0.03 if all but the two highest spH values are used). The speciation of bound 1 at a La3+ concentrations corresponding to that of the onset of the kinetic plateau region was approximated through potentiometric titration of the nonreactive 3,5-dinitrobenzoic acid in the presence of 2 equiv of La(OTf)3. A total speciation diagram for all bound forms of La3+2(1-)(-OCH3)n, where n = 0-5, was constructed and used to determine their kinetic contributions to the overall spH vs kmaxobs plot under kinetic conditions. Two kinetically equivalent mechanisms were analyzed: methoxide attack on La3+2(1-)(-OCH3)n, n = 0-2; unimolecular decomposition of the forms La3+2(1-)(-OCH3)n, n = 1-3.