Mechanism acid-catalyzed ester hydrolysis

The mechanism of acid catalyzed ester hydrolysis is presented m Figure 20 4 It IS precisely the reverse of the mechanism given for acid catalyzed ester formation m Section 19 14 Like other nucleophilic acyl substitutions it proceeds m two stages A... 

On the basis of the general mechanism for acid catalyzed ester hydrolysis shown in Figure 20 4 write an analogous sequence of steps for the spe cific case of ethyl benzoate hydrolysis... 

Kinetic Considerations. Extensive kinetic and mechanistic studies have been made on the esterification of carboxyHc acids since Berthelot and Saint-GiHes first studied the esterification of acetic acid (18). Although ester hydrolysis is catalyzed by both hydrogen and hydroxide ions (19,20), a base-catalyzed esterification is not known. A number of mechanisms for acid- and base-catalyzed esterification have been proposed (4). One possible mechanism for the bimolecular acid-catalyzed ester hydrolysis and esterification is shown in equation 2 (6). 

Although the previous two sections of this chapter emphasized hydrolytic processes, two mechanisms that led to O- or N-acylation were considered. In the discussion of acid-catalyzed ester hydrolysis, it was pointed out that this reaction is reversible (p. 475). Thus, it is possible to acylate alcohols by reaction with a carboxyhc acid. To drive the reaction forward, the alcohol is usually used in large excess, and it may also be necessary to remove water as it is formed. This can be done by azeotropic distillation in some cases. 

FIGURE 20.4 The mechanism of acid-catalyzed ester hydrolysis. Steps 1 through 3 show the formation of the tetrahedral intermediate. Dissociation of the tetrahedral intermediate is shown in steps 4 through 6. 

Acid-catalyzed ester hydrolysis can occur by more than one mechanism, depending on the structure of the ester. The usual pathway, however, is just the reverse of a Fischer esterification reaction (Section 21.3). The ester is first activated toward nucleophilic attack by protonation of the carboxyl oxygen atom, and nucleophilic addition of water then occurs. Transfer of a proton and elimination of alcohol yields the carboxylic acid (Figure 21.8). Because this hydrolysis reaction is the reverse of a Fischer esterification reaction, Figure 21.8 is the reverse of Figure 21.4. 

Active Figure 21.8 MECHANISM Mechanism of acid-catalyzed ester hydrolysis. The forward reaction is a hydrolysis the back-reaction is a Fischer esterification and is thus the reverse of Figure 21.4. Sign in afwww.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

The acid-catalyzed ester hydrolysis provides a good target for MM treatments. DeTar first used hydrocarbon models in which an ester was approximated by an isoalkane (74) and the intermediate (75) by a neoalkane (76). He assumed that if the rate of reaction truly is not influenced by polar effects but is governed only by steric effects of R, as has been generally postulated, the rate must be proportional to the energy difference (AAH ) between 74 and 76. The AAH f is mainly determined by the van der Waals strain in these branched alkanes. Nonsteric group increment terms were carefully adjusted, and statistical mechanical corrections for conformer populations... 

Scheme 1. Mechanism (Aac2) for acid-catalyzed ester hydrolysis.

The first step in acid-catalyzed ester hydrolysis is protonation on oxygen, the same first step of any mechanism involving an oxygen-containing starting material and an acid. 

The first step in the mechanism for acid-catalyzed ester hydrolysis is protonation of the carbonyl oxygen by the acid. Recall that HB" " represents any species in the solution that is capable of donating a proton and =B represents any species in the solution that is capable of removing a proton. 

Now let s see how the acid increases the rate of ester hydrolysis. The acid is a catalyst. Recall that catalyst is a substance that increases the rate of a reaction without being consumed or changed in the overall reaction (Section 4.5). For a catalyst to increase the rate of a reaction, it must increase the rate of the slow step of the reaction. Changing the rate of a fast step will not affect the rate of the overall reaction. Four of the six steps in the mechanism for acid-catalyzed ester hydrolysis are proton transfer steps. Proton transfer to or from an electronegative atom such as oxygen or nitrogen is a fast step. So there are two relatively slow steps in the mechanism formation of a... 

Fig. 15.4 Mechanism for acid-catalyzed ester hydrolysis and carboxylic acid hydrolysis...

In this procedure we shift the equilibrium to the right by allowing the low-boiling alcohol to distill from the reaction mixture. The mechanism for transesterification is similar to that for an acid-catalyzed esterification (or an acid-catalyzed ester hydrolysis). Write a detailed mechanism for the following transesterification ... 

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