Esterification acid-catalyzed addition-elimination

Esterification proceeds through acid-catalyzed addition-elimination... 

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. 

The mechanism for the acid-catalyzed (sulfuric acid) Fischer esterification reaction below is addition, p.t., p.t., elimination write out the mechanism with all its steps. Remember to choose between the three types of additions, AdE2, AdN2, or AdgS, then choose between the three types of eliminations, El, E2, or ElcB. 

The results of the labeling experiment and the fact that esterifications are acid catalyzed are both consistent with the mechanism that follows. This mechanism is typical of acid-catalyzed nucleophilic addition-elimination reactions at acyl carbon atoms. 

For carboxylic acids, the success of an addition-elimination reaction depends on the transformation of the carboxyl hydroxyl group into a better leaving group. This conversion is often done through protonation in acid-catalyzed reactions. The best example is Fischer esterification, and its cyclic variation, lactone formation (Fig. 17.33). 

Esters undergo nucleophilic substitution reactions by means of addition-elimination pathways, albeit with reduced reactivity relative to halides and anhydrides. Thus, catalysis by acid or base becomes a frequent necessity. For example, esters are cleaved to carboxylic acids and alcohols in the presence of excess water and strong acid, and the reaction requires heating to proceed at a reasonable rate. The mechanism of this transformation is the reverse of acid-catalyzed esterification (Section 19-9). As in esterification, the acid serves two purposes It protonates the carbonyl oxygen to make the ester more reactive toward nucleophilic attack, and it protonates the alkoxy oxygen in the tetrahedral intermediate to make it a better leaving group. 

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