39651-54-2Relevant academic research and scientific papers
Metal ion promoted hydroxide ion and water catalyzed hydrolysis of amides. Effects of the acyl group and the leaving group
Fife, Thomas H.,Bembi, Ramesh
, p. 11358 - 11363 (1993)
The hydrolysis of anilide derivatives of N-methyl-4-nitroaniline in H2O is hydroxide ion catalyzed; plots of log kobsd 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 is favorable (kOH' = 1.0 × 104 M-1 s-1 at 50 °C), even though the pKa of the anilide N-H function is 5.5 and the second-order rate constant (kOH') 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 kOH. 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, kOH = 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.
Re-evaluation of Cyclodextrin as a Model of Chymotrypsin: Acceleration and Inhibition of Tertiary Anilide Hydrolysis
Palmer, David R. J.,Buncel, Erwin,Thatcher, Gregory R. J.
, p. 5286 - 5291 (2007/10/02)
The hydrolysis of p-nitro-N-methyltrifluoroacetanilide (1), p-chloro-N-methyltrifluoroacetanilide (2), N-methyltrifluoroacetanilide (3), and p-methoxy-N-methyltrifluoroacetanilide (4) in the presence and absence of α- and β-cyclodextrin has been studied at 7.5 pH 10.6.For 1-3, cyclodextrin (CD) exhibits simple Michaelis-Menten saturation kinetics, with no evidence for reaction via other than 1:1 CD-substrate complexes.The behavior of CD with 4 is more complex.Moreover, CD catalyzes the hydrolysis of 1 but inhibits the hydrolysis of 2-4 across the pH range studied.The nature of the buffer catalysis in the absence of CD, exhibited in the hydrolysis of 1, also shows marked differences with that exhibited by 2-4.The data are almost simply interpreted by a mechanism in which CD accelerates formation of a tetrahedral intermediate 5; in the case of 1, the rate of breakdown of this intermediate is greater than the rate of buffer-catalyzed breakdown of the hydrolysis intermediate.The CD cavity may provide an environment complementary to the transition state for expulsion of the anilide leaving group.These results are compared with the previously reported effects of CDs on trifluoroacetanilide and phenyl ester hydrolysis and proposal of CD as a model of chymotrypsin.
