Reactivity of N-pyridylcarbamates in basic media

Article abstract of DOI:10.1039/b200445n

New secondary aryl N-pyridylcarbamates were prepared by reaction of the aminopyridine anion with aryl chloroformates and their hydrolysis was studied over the pH range from 12 to 13.7. The pH-rate profile points to an E1cB mechanism, involving pre-equilibrium deprotonation of the nitrogen atom to form an anion that undergoes rate-limiting decomposition into pyridyl isocyanate and a phenoxide ion. Further reaction of the highly reactive isocyanate with water affords N-pyridylcarbamic acid, which spontaneously decomposes to aminopyridine and carbon dioxide. The absence of significant base catalysis and the isolation of a new product resulting from trapping of the intermediate with the base piperidine are also consistent with an elimination addition mechanism. Finally the observed substituent effect (σ^-) gives ρ 2.45 which is in accordance with a rate-determining departure of the phenoxide group from the anion intermediate formed in a pre-equilibrium step. Blocking the E1cb mechanism of the secondary carbamates by introduction of N,N-disubstitution in the substrate led to a rate-limiting decrease of ca. 10⁶.