Catalytic intramolecular participation of amide group in the acid hydrolysis of methyl ether linkage

Article abstract of DOI:10.1016/0040-4020(95)00556-N

Evidence for the acid catalyzed hydrolysis or methyl ether linkage assisted by the neighboring amide function was obtained. The hydrolysis rate of 1 to 3 was measured at least 1.7 x 10³ fold higher than that of the reference compound 5. The values of thermodynamic parameters suggest that the participation of neighboring amide group in 1 is accompanied by a lower activation enthalphy with respect to the unassisted reaction in 5. Experimental evidence, such as the kinetic isotope ratio, the positive Φ value of Bunnett-Olsen equation and ΔS++ value suggests an A₂ mechanism.