METAL-ION CATALYSIS OF AMIDE HYDROLYSIS - VERY LARGE RATE ENHANCEMENTS BY COPPER(II) IN THE HYDROLYSIS OF SIMPLE LIGAND-FUNCTIONALIZED TERTIARY AMIDES

The factors which govern the ability of exchange-labile metal ions to catalyze amide hydrolysis remain incompletely understood. Only small rate enhancements have historically been observed for simple coordinating amides such as glycylglycine. This now appears to be a consequence of the formation of hydrolytically inert "amido" chelate complexes in the (neutral) pH range where maximal catalytic effects of metal ions would otherwise be seen. Indeed, rate enhancements of 10(7)-10(8) are induced by Cu(II) for the hydroxide-dependent hydrolysis of N-picolinylsarcosine and other tertiary amides lacking a dissociable NH.