Reverse of Fischer esterification

As indicated by the position of lsO in the product, the acid-catalyzed hydrolysis of r-butyl acetate in water enriched in lsO does not follow the mechanism for the reverse of Fischer esterification, shown in Figure 19.3. Suggest a mechanism that explains the position of the lxO in the product and explain why this mechanism is favored in this case. 

Show how an ester can react with H /H20 to give a carboxylic acid and an alcohol (H/nt This is the reverse of Fischer esterification) ... 

Esters react with water in the presence of an acid catalyst to produce a carboxylic acid and alcohol. The mechanism is exactly the reverse of Fischer esterification, explaining why Fischer esterification is an equilibrium process. 

Ester hydrolysis (Section 18.8) The conversion of an ester into an acid through treatment with an acid catalyst in excess water. The reverse of Fischer esterification. This reaction also occurs in base, and is called saponification in that case. 

The net effect of Fischer esterification is substitution of an -OH group by —OR. Aii steps are reversible, and the reaction can be driven in either direction by choice of reaction conditions. Ester formation is favored when a large excess of alcohol is used as solvent, but carboxylic acid formation is favored when a large excess of water is present. 

Fischer esterification is reversible and the position of equilibrium lies slightly to the side of products when the reactants are simple alcohols and carboxylic acids When the Fis cher esterification is used for preparative purposes the position of equilibrium can be made more favorable by using either the alcohol or the carboxylic acid m excess In the following example m which an excess of the alcohol was employed the yield indicated IS based on the carboxylic acid as the limiting reactant... 

Hydrolysis (Sections 20 10 and 20 11) Ester hydrolysis may be catalyzed either by acids or by bases Acid catalyzed hydrolysis is an equilibrium controlled process the reverse of the Fischer esterification Hydrolysis in base IS irreversible and is the method usual ly chosen for preparative purposes... 

Section 2010 Ester hydrolysis can be catalyzed by acids and its mechanism (Figure 20 4) is the reverse of the mechanism for Fischer esterification The reaction proceeds via a tetrahedral intermediate... 

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. 

This method is called the Fischer esterification. It s a condensation reaction where the loss of a water molecule accompanies the joining of the alcohol portion to the acid portion. The acid gives up the OH and the alcohol gives up the H to make the water molecule. All steps in the mechanism are reversible (that is, it establishes an equilibrium), so removing the ester as soon as it forms is helpful. Removal of the ester is normally easy since esters typically have lower boiling points than alcohols and carboxylic acids. Figure 12-20 illustrates the mechanism for the acid-catalyzed formation of an ester by the reaction of an alcohol with a Ccirboxylic acid. 

Acid hydrolysis is the reverse of the Fischer esterification, seen earlier in the section Acid plus alcohol. Figure 12-34 illustrates the mechanism. 

The acid-catalysed hydrolysis of an ester is the reverse reaction of the Fischer esterification. Addition of excess water drives the equilibrium towards the acid and alcohol formation. The base-catalysed hydrolysis of esters is also known as saponification, and this does not involve the equilibrium process observed for the Fischer esterification. 

Ester hydrolysis is the most studied and best understood of all nucleophilic acyl substitutions. Esters are fairly stable in neutral aqueous media but are cleaved when heated with water in the presence of strong acids or bases. The hydrolysis of esters in dilute aqueous acid is the reverse of the Fischer esterification (Sections 15.8 and 19.14) ... 

Esters can be hydrolyzed to carboxylic acids under either acidic or basic conditions. Under acidic conditions the mechanism is the exact reverse of the Fischer esterification mechanism shown in Figure 19.3. Again, because the acid and the ester have comparable reactivities, some method must be used to drive the equilibrium toward the desired product—the acid in this case. This can be accomplished by using water as the solvent, providing a large excess of this reagent that, by Le Chatelier s principle, shifts the equilibrium toward the carboxylic acid. 

Butyl esters can be cleaved by reaction with dilute acid under milder conditions than those required to hydrolyze a methyl ester. The reaction follows an SNI mechanism, rather than the reverse of the Fischer esterification mechanism, because of the stability of the /-butyl carbocation ... 

First all three ester bonds and both amide bonds are hydrolyzed to carboxylic acid groups by the aqueous acid. The mechanisms for these reactions are discussed in Section 19.5. The ester hydrolyses follow the exact reverse of the Fischer esterification mechanism shown in Figure 19.3, and the amide hydrolysis occurs by a very similar mechanism. The product of these hydrolysis steps has three carboxylic acid groups and one amino group. Two of these acid groups are attached to the same carbon so that one can be eliminated as carbon dioxide by the cyclic mechanism described in Section 20.4 for the malonic ester synthesis ... 

Hydrolysis of ethyl formate follows the reverse path of the Fischer esterification. This part of the mechanism is left to you as an exercise. 

This Fischer esterification reaction reaches equilibrium after a few hours of refluxing. The position of the equilibrium can be shifted by adding more of the acid or of the alcohol, depending on cost or availability. The mechanism of the reaction involves initial protonation of the carboxyl group, attack by the nucleophilic hydroxyl, a proton transfer, and loss of water followed by loss of the catalyzing proton to give the ester. Because each of these steps is completely reversible, this process is also, in reverse, the mechanism for the hydrolysis of an ester ... 

Whereas Z-stilbene is less stable and lower-melting than -stilbene, the reverse is true of the a-carboxylic acids, and in this preparation the more stable, higher-melting -acid is the predominant product. Evidently the steric interference between the carboxyl and phenyl groups in the Z-acid is greater than that between the two phenyl groups in the E-acid. Steric hindrance is also evident from the fact that the Z-acid is not subject to Fischer esterification (ethanol and an acid catalyst) whereas the -acid is. 

---