Base catalysis of ester hydrolysis

E. l Intramolecular general base catalysis of ester hydrolysis 259, E.2 Intramolecular... 

The transition from nucleophilic to general base catalysis of ester hydrolysis has been demonstrated by Kirsch and Jencks300 for attack by imidazole on a series of acetate esters. Their data are given in Table 41, and include a figure for the catalysis by imidazole of the hydrolysis of ethyl acetate. This must... 

General base catalysis of ester hydrolysis by nucleophiles other than amines and oxyanions has not been characterized, though it would be expected to be closely similar to the reaction involving these bases. Cyanide ion, for example, would be expected to catalyze the hydrolysis of ethyl esters with activated acyl groups, such as ethyl dichloroacetate, by this mechanism. 

An alternative mechanism for base catalysis of ester hydrolysis is nucleophilic catalysis, as illustrated in Figure 7.26. In the first step of the reaction, a nucleophile replaces the alkoxy group. In the second step, that nucleophile is replaced by an OH group. The catalytic effect arises if (at the pH of the experiment) Nu is both a more effective nucleophile than hydroxide ion and is also a better leaving group than the alkoxide ion. 

Jencks WP, Carriuolo J (1961) General base catalysis of ester hydrolysis. J Am Chem Soc 83 1743-1750... 

General base and nucleophilic catalysis of ester hydrolysis and related reactions, 5, 237... 

F. l Catalysis of ester hydrolysis 264, F.2 Catalysis of enolization 265 G Intramolecular general base catalysis by nitrogen 266... 

G. 1 Catalysis of ester hydrolysis 266, G.2 Intramolecular general base catalysis of... 

F INTRAMOLECULAR GENERAL BASE CATALYSIS BY PHENOLATE OXYGEN F. 1 Catalysis of 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... 

Gaseous carbonium ions from the decay of tritiated molecules, 8, 79 General base and nucleophilic catalysis of ester hydrolysis and related reactions, 5, The Gomberg Century Free Radicals 1900-2000, 36, 1 Gomberg and the Nobel Prize, 36, 59... 

The hydrolysis of the more reactive carboxylic esters is catalyzed by a wide range of oxyanions. The mechanism proposed for the neutral hydrolysis of esters on p. 158 involves two molecules of water, one as a nucleophile and one as a general base. In principle an oxyanion or other nucleophile can replace either of these molecules, and both general base and nucleophilic catalysis of ester hydrolysis are well-known. The detailed mechanism of nucleophilic catalysis depends, to some extent, on the type of anion concerned, but the differences occur at a relatively late stage in the reaction, and the similarities are sufficient to allow generalizations about oxyanion reactions as a class. Some of the differences are not normally kinetically significant, and are best mentioned briefly at this point. 

The broad outline of the mechanism of catalysis of ester hydrolysis by hydroxide ion is not in doubt. The reaction is well known to involve acyl-oxygen cleavage, and seems invariably to be of the second order, being first order in both ester and hydroxide anion. General base catalysis in the usual sense is not a possibility, the partial removal of a proton from water cannot generate a species more reactive than hydroxide ion, so direct nucleophilic attack must be involved. (However, if it is accepted that the high ionic nobility of the hydroxide ion in water is explained by a Grotthus-type mechanism... 

It is found experimentally that the general-base catalysis of the hydrolysis of an ester is proportional to the basic strength of the catalyst (Figure 2.5).8 The... 

GENERAL BASE AND NUCLEOPHILIC CATALYSIS OF ESTER HYDROLYSIS AND RELATED REACTIONS... 

---