Metal ion promoted hydroxide ion and water catalyzed hydrolysis of amides. Effects of the acyl group and the leaving group

Article abstract of DOI:10.1021/ja00077a039

The hydrolysis of anilide derivatives of N-methyl-4-nitroaniline in H₂O is hydroxide ion catalyzed; plots of log k_obsd 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 10⁴- to 10⁵-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 × 10⁴ M^-1 s^-1 at 50 °C), even though the pK_a of the anilide N-H function is 5.5 and the second-order rate constant (k_OH') is tnat 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 °C, k_OH = 5 × 10⁶ 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 β is 0.3.