Fischer esterification. See

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (see Section 5.5.5). 

Because the acidic hydrogen is the usual cause of undesired reactivity, carboxylic acids are commonly protected as esters. Most often, simple methyl esters are used. The ester can be prepared via the acyl chloride or by Fischer esterification (see Section 19.4). The ester group can be converted back to the carboxylic acid by hydrolysis under acidic or basic (saponification) conditions (see Section 19.5). 

Fischer esterification. See Esterification Esters Fischer projection formulas, 271-272, 278, 280, 292, 595 a-amino acids, 1056, 1103 carbohydrates, 973-974, 1007 of meso stereoisomer, 280 tartaric acids, 286... 

With Fischer esterification and ester hydrolysis, we can see the principle of microscopic reversibility by comparing the mechanism for Fischer esterification. (See Primer II (page 699) and the ester hydrolysis mechanism box immediately... 

Section 20.7 Esters occur naturally or are prepared from alcohols by Fischer esterification or by acylation with acyl chlorides or acid anhydrides (see Table 20.3). 

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 Fischer esterification, named after the eminent German chemist Emil Fischer, is the Bronsted acid-catalyzed reaction of an alcohol with a carboxylic acid to form an ester (see Table 1). Sulfuric acid is often the catalyst. Esters are widely used in the soap, perfume, and food industries. 

The Fischer esterification mechanism (see the Key Mechanism box) is an acid-catalyzed nucleophilic acyl substitution. The carbonyl group of a carboxylic acid is not sufficiently electrophilic to be attacked by an alcohol. The acid catalyst proto-nates the carbonyl group and activates it toward nucleophilic attack. Loss of a proton gives the hydrate of an esto-. 

Complete these examples of Fischer esterification (assume an excess of the alcohol) (See Example 13.5)... 

The experiments described in this chapter illustrate some of the representative reactions of carboxylic acids and their derivatives. For example, you will perform a Fischer esterification, one of the classic reactions in organic chemistry that was discovered by the Nobel laureate Emil Fischer (see the Historical Highlight at the end of Chapter 23 for an account of the life of this famous chemist), to prepare the anesthetic agent benzocaine from p-aminobenzoic acid (Sec. 20.2). In another experiment, you will synthesize the mosquito repellent N,N-diethyl-7n-toluamide (DEET) by a two-step process that involves the conversion of a carboxylic acid into an acid chloride and subsequent reaction with an amine to produce the desired amide (Sec. 20.3). 

You have learned several methods to make carhoxylic acids. We have also discussed how to make esters and amides from organic acids. Notice the similarity between amide formation and ester formation. Amide formation is in fact merely a collection of steps closely resembling those in Fischer esterification. We are beginning to see the generality of the addition—elimination process. The addition—elimination reaction will continue to be prominent throughout this and other chapters. 

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

From carboxylic acids (see Sections 15.8 and 18.14) In the presence of an acid catalyst, alcohols and carboxylic acids react to form an ester and water. This is the Fischer esterification. The yield of ester can be increased beyond the equilibrium amount by removing the water as it is formed. 

Hydrolysis (see Sections 19.8 and 19.9) Ester hydrolysis may be catalyzed either by acids or by bases. Acid-catalyzed hydrolysis is an equilibrium-controlled process and the reverse of the Fischer esterification. Hydrolysis in base, called saponification, Is Irreversible and is the method usually chosen for preparative purposes. 

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