Equilibrium Fischer esterification

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... 

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. 

Preparation of esters Esters are obtained by refluxing the parent carboxylic acid and an alcohol with an acid catalyst. The equilibrium can be driven to completion by using an excess of the alcohol, or by removing the water as it forms. This is known as Fischer esterification. 

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. 

While still useful for large-scale esterification of fairly robust carboxylic acids, Fischer esterification is generally not useful in small-scale reactions because the esterification depends on an acid-catalyzed equilibrium to produce the ester. The equilibrium is usually shifted to the side of the products by adding an excess of one of the reactants—usually the alcohol—and refluxing until equilibrium is established, typically several hours. The reaction is then quenched with base to freeze the equilibrium and the ester product is separated from the excess alcohol and any unreacted acid. This separation is easily accomplished on a large scale where distillation is often used to separate the product from the by-products. For small-scale reactions where distillation is not a viable option, the separation is often difficult or tedious. Consequently Fischer esterification is not widely used for ester formation in small-scale laboratory situations. In contrast, intramolecular Fischer esterification is very effective on a small scale for the closure of hydroxy acids to lactones. Here the equilibrium is driven by tire removal of water and no other reagents are needed. Moreover the closure is favored entropically and proceeds easily. 

This reaction, known as Fischer esterification, requires the presence of an acid catalyst. Because the carboxylic acid and the ester have similar reactivities, the reaction is useful only if a method can be found to drive the equilibrium in the direction of the desired product—the ester. In accord with Le Chatelier s principle, this is accomplished by using an excess of one of the reactants or by removing one of the products. An excess of the alcohol is used if it is readily available, as is the case for methanol or ethanol. Or water can be removed by azeotropic distillation with a solvent such as toluene. 

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. 

RCOH + R OH RCOR Preparation of esters by Fischer esterification. The equilibrium... 

Fischer esterification is an equilibrium, and typical equilibrium constants for esterification are not very large. For example, if 1 mole of acetic acid is mixed with 1 mole of ethanol, the equilibrium mixture contains 0.65 mole each of ethyl acetate and water and 0.35 mole each of acetic acid and ethanol. Esterification using secondary and tertiary alcohols gives even smaller equilibrium constants. 

Driving the Fischer esterification toward a favorable equilibrium is rarely difficult, so this is a common method for making esters, both in the laboratory and in industry. Acid chlorides also react with alcohols to give esters (Section 20-15), but acid chlorides are more expensive, and they are more likely to promote side reactions such as dehydration of the alcohol. 

Propose a mechanism for a Fischer esterification, and show how the equilibrium Problems 20-37, 38, 41, and 47 can be driven toward the products or the reactants. 

Basic hydrolysis of esters, called saponification, avoids the equilibrium of the Fischer esterification. Hydroxide ion attacks the carbonyl group to give a tetrahedral intermediate. Expulsion of alkoxide ion gives the acid, and a fast proton transfer gives the carboxylate ion and the alcohol. This strongly exothermic proton transfer drives the saponification to completion. A full mole of base is consumed to deprotonate the acid. 

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 ... 

As noted above, Fischer esterification is an equilibrium process. Consider the reaction of acetic acid with 1-butanol to give n-butyl acetate ... 

Esterification (Section 15.8) In the presence of an acid catalyst, carboxylic acids and alcohols react to form esters. The reaction is called the Fischer esterification. It is an equilibrium process but can be driven to favor the ester by removing the water that is formed. 

The preparation of thioesters by Fischer esterification is not very effective, however, because the equilibrium is normally unfavorable. Under conditions in which ethanol is converted to ethyl benzoate to the extent of 68%, ethanethiol gives only 15% ethyl thiobenzoate. 

Fischer esterifications proceed very slowly in the absence of strong acids, but they reach equilibrium within a matter of a few hours when an acid and an alcohol are refluxed with a small amount of concentrated sulfuric acid or hydro n chloride. Since the position of equilibrium controls the amount of the ester formed, the use of an excess of either the carboxylic add or the alcohol increases the yield based on the limiting reagent. Just which component we choose to use in excess will depend on its availability and cost. The yield of an esterification reaction can also be ino-eased by removing water from the reaction mixture as it is formed. 

Acid-catalyzed esterification is reversible, and generally, at equilibrium, the quantities of remaining carboxylic acid and alcohol are appreciable. By controlling the experimental conditions, however, we can use Fischer esterification to prepare esters in high yields. If the alcohol is inexpensive compared with the carboxylic acid, we can use a large excess of the alcohol to drive the equilibrium to the right and achieve a high conversion of carboxylic acid to its ester. 

The process is called Fischer esterification after Emil Fischer (page 163), who developed the method. Although the reaction is an equilibrium, it can be shifted to the right in several ways. If either the alcohol or the acid is inexpensive, a large excess can be used. Alternatively, the ester and/or water may be removed as formed (by distillation, for example), thus driving the reaction forward. 

Fischer esterification reaction, 197-208 as equilibrium reaction, 198 mechanism, 197-199 with primary alcohols, 198 theory, 196-197... 

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