Fischer esterification reaction mechanism

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. 

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. 

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... 

Emil Fischer was the first to discover that an ester could be prepared by treating a carboxylic acid with excess alcohol in the presence of an acid catalyst, so the reaction is called a Fischer esterification. Its mechanism is the exact reverse of the mechanism for the acid-catalyzed hydrolysis of an ester shown on page 742. Also... 

The mechanisms of the Fischer esterification and the reactions of alcohols with acyl chlorides and acid anhydrides will be discussed m detail m Chapters 19 and 20 after some fundamental principles of carbonyl group reactivity have been developed For the present it is sufficient to point out that most of the reactions that convert alcohols to esters leave the C—O bond of the alcohol intact... 

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... 

Mechanism of Fischer esterification. The reaction is an acid-catalyzed, nucleophilic acyl substitution of a carboxylic acid. 

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. 

Tanaka and Kakiuchi (6) proposed catalyst activation via a hydrogen donor such as an alcohol as a refinement to the mechanism discussed by Fischer (7) for anhydride cured epoxies in the presence of a tertiary amine. The basic catalyst eliminates esterification reactions (8). Shechter and Wynstra ( ) further observed that at reaction conditions BDMA does not produce a homopolymerization of oxiranes. 

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. 

Transesterification Transesterification occurs when an ester is treated with another alcohol. This reaction can be acid catalysed or base catalysed. This is where the alcohol part of the ester can be replaced with a new alcohol component. The reaction mechanism is very similar to the Fischer esterification. 

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 ... 

Most of the Fischer esterification mechanism is identical with the mechanism of acetal formation. The difference is in the final step, where a carbocation loses a proton to give the ester. Write mechanisms for the following reactions, with the comparable steps directly above and below each other. Explain why the final step of the esterification (proton loss) cannot occur in acetal formation, and show what happens instead. 

The mechanism of the Fischer esterification was controversial until 1938, when Irving Roberts and Harold Urey of Columbia University used isotopic labeling to follow the alcohol oxygen atom through the reaction. A catalytic amount of sulfuric acid was added to a mixture of 1 mole of acetic acid and 1 mole of special methanol containing the heavy lsO isotope of oxygen. After a short period, the acid was neutralized to stop the reaction, and the components of the mixture were separated. 

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