Metal ion-assisted intramolecular nucleophilic attack of the amide oxygen at ester linkages in 2-pyridineoxime esters of ( Z)-α-(acetylamino)cinnamic acid

Abstract

Kinetics of the cyclization of 2-pyridinecarboxaldoxime ester ( 1a) or 2-acetylpyridineketoxime ester ( 1b) of ( Z)-α-(acetylamino)cinnamic acid were measured in the presence and absence of divalent metal ions (Zn(II), Ni(II), and Cu(II)). Rate data for the hydrolysis of 2-acetylpyridineketoxime ( E)-cinnamate were obtained in the presence and absence of Ni(II) or Cu(II) ion. The kinetic data measured in the presence of a divalent metal ion were analyzed in terms of complexation of the substrate with the metal ion and the subsequent conversion of the complex into products. Comparison of the rate data indicated that the metal ions catalyze the cyclization of 1a and 1b by enhancing the leaving ability of the oximate anions. The degree of acceleration of the expulsion of 2-acetylpyridineketoxime achieved by the bifunctional participation of Ni(II) ion and the amide group was much greater than the multiplication product of those achieved individually by Ni(II) ion and the amide group. The efficient cooperation between the metal ion and the amide group may also operate in the action of enzymes.