METAL-ION PROMOTED HYDROXIDE ION AND WATER CATALYZED-HYDROLYSIS OF AMIDES - EFFECTS OF THE ACYL GROUP AND THE LEAVING GROUP

The hydrolysis of anilide derivatives of N-methyl-4-nitroaniline in H2O is hydroxide ion catalyzed; plots of log k(obd) vs pH are linear with slopes of 1.0 at pH > 8. When there is a chelating functional group in the acyl portion of the molecule (1, 10-phenanthrolinyl or 6-carboxypicolinoyl) and in the presence of saturating concentrations of Cu2+, Co2+, or Zn2+, hydroxide ion catalyzed reactions are observed at pH > 4 (rate enhancements range from 10(4)- to 10(5)-fold), and pH-independent reactions occur from pH 1 to 4. Rate constants are very nearly the same in the metal ion promoted hydrolysis reactions for the anilides with these acyl groups. Thus, the negatively charged carboxylate ligand of N-(6-carboxypicolinoyl)-N-methyl-4-nitroaniline is equally good in facilitating the metal ion promoted hydrolysis reactions as the neutral ligands of the 1, 10-phenanthroline derivative. A trifluoroacetyl acyl group produces the same general effect as a chelated metal ion, i.e., a facile OH--catalyzed reaction and a pH-independent reaction at pH < 6. The metal ions very likely exert their principal effect in a similar manner, by strong electron withdrawal from the carbonyl group. The hydroxide ion catalyzed hydrolysis of N-(trifluoroacetyl)-2,4-dinitroaniline at pH > 6 is favorable (k(OH)' = 1.0 X 10(4) M-1 s-1 at 50-degrees-C), even though the pK(a) of the anilide N-H function is 5.5 and the second-order rate constant (k(OH)') is that for attack of OH- on the ionized species. Amide deprotonation does not have a large effect on the rate of hydrolysis; ionization of the amide N-H function of N-(trifluoroacetyl)-2-carboxy-4-nitroaniline produces only a 7-fold decrease in k(OH). An N-methyl group accelerates the rate of hydrolysis of the (trifluoroacetyl)-2,4-dinitroanilide. N-(Trifluoroacetyl)-N-methyl-2,4-dinitroaniline hydrolyzes very rapidly at 50-degrees-C, k(OH) = 5 X 10(6) M-1 s-1 and k0 = 10(-2) s-1. The pH-independent reaction governed by k0 proceeds 2. 1 -fold more slowly in D2O than in H2O. General base catalysis occurs, and the Bronsted coefficient beta is 0.3.