Theoretical studies on the acid hydrolysis of methyl carbamate

The mechanism of the A2 acid hydrolysis of methyl carbamate was investigated using MNDO method. The reaction was found to proceed in two steps: (1) the rate-determining nucleophilic attack of water on the carbonyl carbon of the N-protonated tautomer involving the tetrahedral TS; and (2) the fast subsequent proton abstraction by the leaving group, NH₃, to form products. The mechanism is similar to that involved in the A2 hydrolysis of acetamide. Effects of substituents, R¹, R², and R³ in R¹OCONR²R³, on rates can be predicted by the changes in electron densities on alkoxy oxygen and N, in complete agreement with the experimental results. We concluded that there is no need for invoking two different mechanisms for amides and carbamates since a common mechanism can easily accommodate all the experimental results.