Base catalysis ester hydrolysis

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... 

The reaction of an amine with an ester generally produces an amide, and catalysis of hydrolysis occurs only in two special situations. Tertiary amines cannot give amides, and may act as nucleophiles or general bases to catalyze ester hydrolysis, and general base catalysis of hydrolysis may be observed with any amine, as long as competing reactions (in particular aminolysis) are relatively slow. 

Intramolecular general base catalysis of hydrolysis (21a) was unexpected since the ester has a phenolic leaving group. Felton and Bruice (1968, 1969) reasoned that, if nucleophilic attack occurred, the leaving phenolate ion group would be properly positioned to attack the intermediate acylimidazole and thereby reverse the reaction. The normally less efficient general base reaction then becomes the favoured pathway, as in hydrolysis of acetyl salicylate (see Section 4). Likewise, Fife and McMahon (1970) explained bimolecular general base catalysis by imidazole (21b) in hydrolysis of o-(4-nitrophenylene) carbonate = 3-49) by reversibility... 

A catalyst is defined as a substance that influences the rate or the direction of a chemical reaction without being consumed. Homogeneous catalytic processes are where the catalyst is dissolved in a liquid reaction medium. The varieties of chemical species that may act as homogeneous catalysts include anions, cations, neutral species, enzymes, and association complexes. In acid-base catalysis, one step in the reaction mechanism consists of a proton transfer between the catalyst and the substrate. The protonated reactant species or intermediate further reacts with either another species in the solution or by a decomposition process. Table 1-1 shows typical reactions of an acid-base catalysis. An example of an acid-base catalysis in solution is hydrolysis of esters by acids. 

Poly(L-malate) decomposes spontaneously to L-ma-late by ester hydrolysis [2,4,5]. Hydrolytic degradation of the polymer sodium salt at pH 7.0 and 37°C results in a random cleavage of the polymer, the molecular mass decreasing by 50% after a period of 10 h [2]. The rate of hydrolysis is accelerated in acidic and alkaline solutions. This was first noted by changes in the activity of the polymer to inhibit DNA polymerase a of P. polycephalum [4]. The explanation of this phenomenon was that the degradation was slowest between pH 5-9 (Fig. 2) as would be expected if it were acid/base-catalyzed. In choosing a buffer, one should be aware of specific buffer catalysis. We found that the polymer was more stable in phosphate buffer than in Tris/HCl-buffer. 

A reaction with a rate constant that conforms to Eq. (10-21)—particularly to the feature that the catalysts are H+ and OH-, and not weak acids and bases—is said to show specific acid-base catalysis. This phenomenon is illustrated by the kinetic data for the hydrolysis of methyl o-carboxyphenyl acetate16 (the methyl ester of aspirin— compare with Section 6.6) ... 

The same framework of eight possible mechanisms that was discussed for ester hydrolysis can also be applied to amide hydrolysis. Both the acid- and base-catalyzed hydrolyses are essentially irreversible, since salts are formed in both cases. For basic catalysis the mechanism is Bac2-... 

Base catalysis, general, of ester hydrolysis and related reactions, 5, 237 Basicity of unsaturated compounds, 4, 195... 

Catalysis, enzymatic, physical organic model systems and the problem of, 11,1 Catalysis, general base and nucleophilic, of ester hydrolysis and related reactions, 5,237 Catalysis, micellar, in organic reactions kinetic and mechanistic implications, 8,271 Catalysis, phase-transfer by quaternary ammonium salts, 15,267 Catalytic antibodies, 31,249... 

Ester hydrolysis, general base and nucleophilic catalysis, 5,237... 

In aqueous solution, the rates of many reactions depend on the hydrogen-ion (H+ or h3o+) concentration and/or on the hydroxyl-ion (OH-) concentration. Such reactions are examples of acid-base catalysis. An important example of this type of reaction is esterification and its reverse, the hydrolysis of an ester. 

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