Catalyzed hydrolysis of esters

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Figure 2.6 Mechanism of lipase-catalyzed hydrolysis of esters [34].

Taft was also able to isolate steric effects. For the acid-catalyzed hydrolysis of esters in aqueous acetone, long (kJh was shown to be insensitive to polar effects. In cases where resonance interaction was absent, this value was proportional only to steric effects (and any others that are not field or resonance). The equation is... 

Syntheses of aliphatic polyesters by fermentation and chemical processes have been extensively studied from the viewpoint of biodegradable materials science. Recently, another approach to their production has been made by using an isolated lipase or esterase as catalyst via non-biosynthetic pathways under mild reaction conditions. Lipase and esterase are enzymes which catalyze hydrolysis of esters in an aqueous environment in living systems. Some of them can act as catalyst for the reverse reactions, esterifications and transesterifications, in organic media [1-5]. These catalytic actions have been expanded to... 

FIGURE 6.3 Mechanism for esterase-catalyzed hydrolysis of esters and amides. 

Lipases can catalyze hydrolysis of esters, synthesis of esters, trans-esterification, and synthesis of some polymers. They have been applied in many fields including the food industry, fine chemistry, and the pharmaceutical industry. The low stability of native lipases makes them unsuitable for industrial applications. In order to use them more economically and efficiently, their operational stability can be improved by immobilization. Numerous efforts have been focused on the preparation of lipases in immobilized forms involving a variety of both support materials and immobilization methods [278],... 

In proton-catalyzed hydrolysis (specific acid catalyzed hydrolysis), protonation of the carbonyl O-atom leads to polarization of the carbonyl group, facilitating addition of the nucleophile, i. e., a H20 molecule (Fig. 3.1, Pathway a). The acid-catalyzed hydrolysis of esters is reversible because the neutral alcohol or phenol released is nucleophilic, whereas hydrolysis of amides is irreversible because the amine released is protonated in the acidic medium and, hence, has considerably reduced nucleophilicity. 

Fig. 7.2. a) The most common mechanism of base-catalyzed ester hydrolysis, namely specific base catalysis (HCT catalysis) with tetrahedral intermediate and acyl cleavage. Not shown here are an W mechanism with alkyl cleavage observed with some tertiary alkyl esters, and an 5n2 mechanism with alkyl cleavage sometimes observed with primary alkyl esters, particularly methyl esters, b) Schematic mechanism of general base catalysis in ester hydrolysis. Intermolecular catalysis (bl) and intramolecular catalysis (b2). c) The base-catalyzed hydrolysis of esters is but a particular case of nucleophilic attack. Intermolecular (cl) and intramolecular (c2). d) Spontaneous (uncatalyzed) hydrolysis. This becomes possible when the R moiety is... 

Parenthetically, it should be noted that there is evidence for the accumulation of an acylenzyme (i.e., a mixed anhydride with Glu-270) in the carboxypeptidase A-catalyzed hydrolysis of esters at low temperature, but this evidence does not include confirmation by chemical trapping experiments (Makinen et al, 1979 Kuo and Makinen, 1982 Suh et al., 1985). This would imply a nucleophilic, rather than promoted-water, pathway for ester hydrolysis. Sander and Witzel (1985) provided the only... 

The mechanism for esterification given in Problem 16.16 is reversible, the reverse being the mechanism for acid-catalyzed hydrolysis of esters. As an example of the principle of microscopic reversibility, the forward and reverse mechanisms proceed through the same intermediates and transition states. 

Metal Ion-Catalyzed Hydrolysis of Esters, Amides, and Thiol Esters... 

Before we turn to discussing neutral and base-catalyzed hydrolysis of ester functions, we need to reflect on what structural features determine how good a leaving... 

One of the characteristics of the acid-catalyzed hydrolysis of esters, that is shared by ester formation also, is that substituent effects on the rate coefficients are small, and not simply related to a values (see below, p. 131). The data in Table 14 show that this is also true for the, sO-exchange reaction of substituted benzoic acids. This is borne out by the relative constancy of the ratio khyJkexch for the different substituted acids it was not possible to obtain a meaningful p value from the data of Table 14, because of the small number of points and the large amount of scatter evident on the Hammett plot. Mesitoic acid is highly unreactive, compared with the m- and p-substi-tuted esters used, as is its methyl ester towards alkaline hydrolysis138, and presumably reacts by the seriously hindered Aac2 route. 

Acid-catalyzed hydrolysis of esters is the reverse of acid-catalyzed ester formation discussed previously. Base-induced ester hydrolysis (saponification) is an irreversible reaction. The initial step is the attack of hydroxide ion at the carbonyl carbon ... 

Now that the steric parameter can be evaluated, the inductive parameter is available. Taft noted that the transition-state structures for acid- and base-catalyzed hydrolysis of esters (15 and 16, respectively) differ from each other by only tiny protons. Therefore the steric effect of a substituent should be approx-... 

Charton, M. Steric Effects I. Esterification and Acid-Catalyzed Hydrolysis of Esters. J. Am. Chem. Soc. 1975, 91, 1552-1556. 

Hydrolytic enzymes such as lipases catalyze hydrolysis of esters in aqueous media, but when used in non-aqueous media such as organic solvents, ionic liquids and supercritical fluids, they catalyze reverse reactions the synthesis of esters. For example, lipases in natural environment catalyze the hydrolysis of fatty acid esters as shown in Figure 6(a). However, when they are used in organic solvents, they catalyze the esterification reaction (Figure 6(b)). 

Acetal resins are generally stable in mildly alkaline environments. However, bases can catalyze hydrolysis of ester end groups, resulting in a less thermally stable polymer. 

A relatively low pH (pH 4.5) was necessary to obtain a selective MIP-catalyzed hydrolysis of ester 77 (Scheme 13.19) this was most likely due to the involvement of the carboxylic acid moieties in substrate binding. In addition, at this pH, the... 

Fig. 11.17. Optional (S)- or (R)-selectivity in the lipase-catalyzed hydrolysis of ester 9 [9, 42,43,75],...

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