Hydrolysis solvent kinetic isotope effects

The carboethoxy stabilized secondary enamines, 25 and 26, were studied by Guthrie and Jordan68. In the absence of buffer, and at pH 5 to 6, acid catalysis is evident and a solvent kinetic isotope effect, (kH+/kD+) = 2.3, is found for 25. These results clearly support rate-controlling C-protonation of the enamine the catalytic constants are included in Table 9. Both 25 and 26 show general-acid catalysis of hydrolysis in the pH... 

Further evidence for the Aa11 mechanism was obtained from a solvent kinetic isotope study. The theoretical kinetic isotope effects for intermediates in the three reaction pathways as derived from fractionation factors are indicated in parentheses in Scheme 6.143,144 For the Aa11 mechanism (pathway (iii)) a solvent KIE (/ch2o A d2o) between 0.48 and 0.33 is predicted while both bimolecular processes (pathways (i) and (ii)) would have greater values of between 0.48 and 0.69. Acid-catalysed hydrolysis of ethylene oxide derivatives and acetals, which follow an A1 mechanism, display KIEs in the region of 0.5 or less while normal acid-catalysed ester hydrolyses (AAc2 mechanism) have values between 0.6 and 0.7.145,146... 

Recently, Noyce and Pollack306 have found kinetic evidence for a changeover from acyl to alkyl-oxygen cleavage in the hydrolysis of a-acetoxystyrenes. At low acidities (1 M H2S04) compounds with electron-withdrawing substituents are hydrolyzed in a reaction which behaves as expected for the Aac2 mechanism. The solvent deuterium isotope effect, kH/kD = 0.75, and the effect of substituents on the rate is small. As the acidity of the medium is increased... 

The kinetics of hydrolysis of N-salicylidene-2-aminothiazole (119 = HL) have been studied in aqueous 5% methanol in the presence and absence of Co11, Ni, Cu11 and Zn11.408 The solvent deuterium isotope effect on the rate of spontaneous and hydroxide-catalyzed hydrolysis of the Schiff-base anion (L ) is consistent with intramolecular catalysis by the phenoxide ion. Only... 

Solvent D2O kinetic isotopic effect kn/ko > 2 for general base, 0.8-1.9 for nucleophilic catalysis (usually) W D = 3,1 for imidazole-catalyzed hydrolysis of ethyl trifluorothiolacetate 90... 

Both a- and p-NeuNAcOPNP hydrolyse through four processes the spontaneous departure of the phenolate from the substrate anion, an acid-catalysed process of the neutral molecule, a base-catalysed process of the anion and an apparently spontaneous process of the neutral molecule. This last process was shown to be the kinetically equivalent acid-catalysed hydrolysis of the anion of p-NeuNAcOAr by a jSig value of 0.14, and of the anion of a-NeuNAcOAr by a jSig value of 0.00 and a solvent deuterium kinetic isotope effect of 0.96, when any intramolecular general acid catalysis would give rise to negative jSig values and direct solvent isotope effects. 

Several studies on intramolecular catalysis of the solvolysis of phosphate esters have been reported. The larger hydrolysis rate of the zwitterion of 8-hydroxyquinoline phosphate (20) compared with that of pyridyl 3-phosphate (21) was attributed, on the basis of the kinetic isotope effect, to intramolecular general acid catalysis. A similar general acid catalysis by the hydroxy-group seems to operate in the (3-hydroxy-2-pyridyl)methyl phosphate dianion (22), which hydrolyses faster than either the monoanion or the neutral molecule. From a study of 4- and 5-substituted derivatives of salicyl phosphate (23) it is suggested that the negligible solvent isotope effect is inconsistent with preliminary proton transfer, and that here also intramolecular general acid catalysis by the... 

An often occurring mechanistic problem is the diagnosis of general base or nucleophilic catalysis which give identical kinetics. Imidazole is a well known catalyst for the hydrolysis of 4-nitrophenyl acetate in water and it is known to involve nucleophilic attack because iV-acetylimidazole has been observed from ultraviolet spectral work [17]. The absence of a solvent deuterium isotope effect confirms the operation of the nucleophilic pathway (Table 7) because a primary isotope effect is expected for the general base mechanism. 

It is noteworthy that there is a pH-independent water reaction in the hydrolysis of compound XLIII [126]. That this involves general acid catalysis by a water molecule is shown by the strongly negative entropy of activation ( — 21 eu) and a solvent deuterium kinetic isotope effect = 1.61). Effective general acid... 

This variation from the ester hydrolysis mechanism also reflects the poorer leaving ability of amide ions as compared to alkoxide ions. The evidence for the involvement of the dianion comes from kinetic studies and from solvent isotope effects, which suggest that a rate-limiting proton transfer is involved. The reaction is also higher than first-order in hydroxide ion under these circumstances, which is consistent with the dianion mechanism. 

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