Esterification reactions, Fischer

Esters can also be synthesized by an acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol, a process called the Fischer esterification reaction. Unfortunately, the need to use an excess of a liquid alcohol as solvent effectively limits the method to the synthesis of methyl, ethyl, propyl, and butyl esters. 

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. 

Fischer esterification reaction (Section 21.3) The acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol to yield an ester. 

Diels-Alder reaction, 493 El reaction, 391-392 ElcB reaction, 393 E2 reaction, 386 Edman degradation, 1032 electrophilic addition reaction, 147-148. 188-189 electrophilic aromatic substitution, 548-549 enamine formation, 713 enol formation, 843-844 ester hydrolysis, 809-811 ester reduction, 812 FAD reactions. 1134-1135 fat catabolism, 1133-1136 fat hydrolysis, 1130-1132 Fischer esterification reaction, 796 Friedel-Crafts acylation reaction, 557-558... 

Step 3 Fischer esterification (reaction of a carboxylic acid with excess alcohol and a strong acid catalyst). 

Fischer esterification reaction. Thus, reaction of cyclohexanol with benzoyl chloride is the preferred method for preparing cyclohexyl benzoate. 

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 ... 

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. 

Steps (1) and (2) are the aldol condensation between the thioester (acetyl CoA) and the keto group of oxaloacetic acid. Step (3) is a reverse Fischer esterification reaction the ester is hydrolyzed to form the carboxylic acid and the thiol, CoA-SH. 

SYNTHESIS The first step involves the s)mthesis of the amino acid 7-benzyl-L-glutamate by a standard Fischer esterification reaction of L-glutamic acid with benzyl alcohol in the presence of strong acid. The amino acid is subsequently converted to the N-carboxyanhydride (NCA) monomer by reaction with phosgene gas, or by reaction with the less hazardous compound triphosgene.The NCA is polymerized by initiation with a variety compounds such as primary and secondary amines, and alkoxides. Typical comonomers include other amino acid NCAs. 

Show how each of the esters in the table can be synthesized using a Fischer esterification reaction. 

Show how each sunscreen can be synthesized from a carboxylic acid and alcohol using the Fischer esterification reaction (Section 13.6). 

The Fischer esterification reaction, shown in Scheme 9, has been investigated by a number of groups using different imidazolium and pyridinium PILs and SO3H functionalized Bronsted acidic AILs as solvents and catalysts. The conversions, selectivities, and reaction conditions are summarized in Table 7. Generally, the conversions and selectivities were very good, though some of the ILs trialed did not promote the reaction. 

Mechanism of the Fischer Esterification Reaction. The Fischer esterification proceeds by nucleophilic attack of the alcohol on the protonated carbonyl group of the carboxylic acid to form a tetrahedral intermediate. Collapse of the tetrahedral intermediate regenerates the carbonyl group and produces the ester and water. The overall sequence is outlined here ... 

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

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