Acid catalysis of ester hydrolysis

Hydrophobic attractive interactions between a polymer and a small-molecule reactant often occur in reactions carried out in aqueous media [Imanishi, 1979 Morawetz, 1975 Overber-ger and Guterl, 1978, 1979]. Acid catalysis of ester hydrolysis by polysulfonic acids is most... 

However, in these reactions it is likely that breakdown of the tetrahedral intermediate is at least partly rate determining so the general acid catalysis is probably associated with this step rather than with attack of the nucleophile on the carbonyl group. The only example of general acid catalysis of ester hydrolysis where the rate limiting step is probably nucleophilic attack on the carbonyl group appears to be the hydrolysis of tetra-O-methyl-D-glucono-... 

Acid catalysis of ester hydrolysis is also very effective. Oxygen exchange from water is observed under most cases, supporting addition-elimination. Specific-acid catalysis is the most common mode of hydrolysis, although general-acid catalysis is observed with more electrophilic esters. 

The existence of attractive interactions between the polymer and the reagent is a classical phenomenon, particularly in aqueous media. Thus, acid catalysis of ester hydrolysis by sulfonic acids is most effective when either the ester or the poly(sulfonic acid) contains hydrophobic groups as this increases the concentration of the small reactants in the polymer domains where there is a high local hydrogen ion concentration. 

Fig. 7.1. a) Specific acid catalysis (proton catalysis) with acyl cleavage in ester hydrolysis. Pathway a is the common mechanism involving a tetrahedral intermediate. Pathway b is SN1 mechanism observed in the presence of concentrated inorganic acids. Not shown here is a mechanism of alkyl cleavage, which can also be observed in the presence of concentrated inorganic acids, b) Schematic mechanism of general acid catalysis in ester hydrolysis. 

Evidence comes from comparative rate studies.216 Thus 71 was hydrolyzed about 105 times faster than benzamide (PhCONH2) at about the same concentration of hydrogen ions. That this enhancement of rate was not caused by the resonance or field effects of COOH (an electron-withdrawing group) was shown by the fact both o-nitrobenzamide and terephthal-amic acid (the para isomer of 71) were hydrolyzed more slowly than benzamide. Many other examples of neighboring-group participation at a carbonyl carbon have been reported.2 7 It is likely that nucleophilic catalysis is involved in enzyme catalysis of ester hydrolysis. 

The extent of the apparent acid catalysis of the hydrolysis of this ester, like... 

A reaction exhibiting general acid catalysis, the ester hydrolysis (XXXVIII), has been discussed in Sect. 2.3. The present section deals with a classic reaction which is subject to both general acid and base catalysis in homogeneous media, the mutarotation of D-glucose. 

Catalysis of ester hydrolysis by metal cations is not restricted to esters of organic acids. Both magnesium(n) and zinc(n) cause marked rate enhancements of hydrolysis of phosphate diesters. Here there is parallel hydrolysis of the free ester and of its metal complex under the conditions examined. ... 

FIGURE 23.2 Catalysis of ester hydrolysis by acids or bases. 

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

Lipases are the enzymes for which a number of examples of a promiscuous activity have been reported. Thus, in addition to their original activity comprising hydrolysis of lipids and, generally, catalysis of the hydrolysis or formation of carboxylic esters [107], lipases have been found to catalyze not only the carbon-nitrogen bond hydrolysis/formation (in this case, acting as proteases) but also the carbon-carbon bond-forming reactions. The first example of a lipase-catalyzed Michael addition to 2-(trifluoromethyl)propenoic acid was described as early as in 1986 [108]. Michael addition of secondary amines to acrylonitrile is up to 100-fold faster in the presence of various preparations of the hpase from Candida antariica (CAL-B) than in the absence of a biocatalyst (Scheme 5.20) [109]. 

The study of both carbonyl and carbon acid participation in ester hydrolysis has been used by Bowden and Last (1971) to evaluate certain of the factors suggested for important roles in enzymic catalysis. A first model concerns a comparison of the three formyl esters and shows that the proximity of the formyl to the ester group and internal strain increase in passing along the series, 1,2-benzoate, 1,8-naphthoate and 4,5-phenanthroate. The very large rate enhancements result from the proximity of the internal nucleophile once formed and from internal strain. Strain is increased or induced by the primary... 

Mineral surfaces may accelerate the rate of ester hydrolysis (Stone, 1989 Hoffmann, 1990 Torrents and Stone, 1991). One plausible scheme for this heterogeneous catalysis assumes a nucleophilic addition of the ester to the surface functional group, e.g., in case of a carboxylic acid ester... 

There are many enzymes that have a specific binding site Ca in the active center and for which Ca has an essential role in catalysis. An example of a Ca -dependent enzyme is phospholipase A2. Phosphohpase A2 catalyses the hydrolysis of fatty acid esters at the 2 position of phosphohpids (see Fig. 5.24), whereby Ca plays an essential role. The enzyme has two Ca ions boimd tightly at the active center. One of the two Ca ions is directly involved in catalysis. It binds the substrate in the groimd state and also helps to neutralize charge in the transition state of ester hydrolysis. The second Ca ion is assigned a role in stabilization of the transition state, in addition to a structural fimction (White et al., 1990). 

Amides. Metal ions catalyze the hydrolysis of a variety of amides, including acylamino acids, dipeptides and tripeptides, and amino acid amides. In all these compounds it is possible for a metal ion to complex with one or more ligand groups, either amine or carboxylate ion functions, in addition to the amide group. Thus the structural prerequisites for the metal ion catalysis of amide hydrolysis are the same as those for ester hydrolysis. 

This sensitivity to substitution of neutral hydrolysis means that the pH-independent reaction gradually becomes more important than the hydroxide reaction at the high pH end of the region, and becomes much more rapidly more important than acid-catalyzed hydrolysis at low pH. Thus from Fig. 13, the acid-catalyzed reaction can be seen to be significant for the hydrolysis of ethyl acetate between pH 4 and 5, and for phenyl acetate about pH 2 but for 2,4-dinitrophenyl acetate the acid-catalyzed reaction is not detectable at pH 1, and is presumably important only in relatively strong acid. It seems certain that this fast neutral hydrolysis is at any rate a partial explanation for the low efficiency of acid catalysis in the hydrolysis of very weakly basic esters, such as the trifluoroacetates and oxalates, in moderately concentrated acid (see p. 145). 

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