Mechanism of esters

FIGURE 20 5 The mechanism of ester hydrolysis in basic solution... 

The mechanism of ester (and lactone) reduction is similar to that of acid chloride reduction in that a hydride ion first adds to the carbonyl group, followed by elimination of alkoxide ion to yield an aldehyde. Further reduction of the aldehyde gives the primary alcohol. 

See the lUPAC rules Guthrie, R.D. Pure Appl. Chem., 1989, 61, 23. As given here, the lUPAC designations for BacI and BalI are the same, but Rule A.2 adds further symbols so that they can be distinguished Su-AL for BalI and Su-AC for BacI- por reviews of the mechanisms of ester hydrolysis and formation, see Kirby, A.J. in Bamford Tipper, Ref 193, vol. 10, 1972, p. 57 Euranto, E.K. in Patai, Ref 216, p. 505. This is an Sn 1 mechanism with OR as leaving group, which does not happen. 

Suggest syntheses for TMs (9) and (10) needed as intermediates TM (9) in the synthesis of brominated hydroxy benzoic acids and TM (10) in the synthesis of model compounds for studying biological mechanisms of ester hydrolysis,... 

Before discussmg the mechanism of cleavage of carboxylic acid esters and amides by hydrolases, some chemical principles are worth recalling. The chemical hydrolysis of carboxylic acid derivatives can be catalyzed by acid or base, and, in both cases, the mechanisms involve addition-elimination via a tetrahedral intermediate. A general scheme of ester and amide hydrolysis is presented in Fig. 3. / the chemical mechanisms of ester hydrolysis will be... 

Although the mechanism of ester formation has been the subject of some controversy, this process is related to polyborate formation in that both cases likely involve nucleophilic attack of an HO oxygen on B(OH)3 followed by elimination of water from a tetrahedral intermediate, Eq. (4). 

Scheme 5.3 (a) Mechanism of ester and anilide ethanolysis catalyzed by dinuclear complexes, showing productive (II) and non-productive (I and III) species and (b) the corresponding intermolecular model reaction based on monomolecular complexes. 

So far we have described reactions strictly in terms of their reactants and products. That doesn t tell us much about how or why a reaction proceeds from reactants to products. The reaction mechanism sometimes is quite a complex process, and for many well-known reactions we still don t understand the mechanism. We confine this discussion to consideration of the relatively simple mechanism of ester hydrolysis. Ester hydrolysis entails the reaction of a water molecule with an ester, leading to the production of an alcohol and a carboxylic acid. It is depicted in equation 1, going from right to left. 

The mechanisms of ester hydrolysis are distinguished with abbreviations of the type medium.. .., . , , reaction order. The medium of acid-catalyzed hydroly-... 

Camino G, Costa L, Trossarelli L, Costanzi F, Pagliari A. Study on the mechanism of intumescence in fire retardant polymers. 6. Mechanism of ester formation in ammonium polyphosphate pentaerythritol mixtures. Polym. Degrad. Stab. 1985 12 213-228. 

The reaction proceeds via the normal six-membered transition state mechanism of ester elimination. The intermediate chlorobutyric acid yielded butyrolactone through participation of the COOH group under the reaction conditions. The pure chlorobutyric acid was pyrolyzed and gave butyrolactone in quantitative yield. The mechanism is similar to that of bromobutyric acid pyrolysis (equation 76). The data are shown in Table 23. 

With this reaction as a model, you should be able to work out the mechanism of ester formation from acetic anhydride and cyclohexanol. Try to write it down without looking at the acyl chloride mechanism above, and certainly not at the answer below. Here it is, with pyridine as the base. Again, addition of the nucleophile gives an unstable intermediate, which undergoes an elimination reaction, this time losing a carboxylate anion, to give an ester. 

The mechanism is very similar to the mechanism of ester formation. 

Mechanism Mechanism of esters reduction involves the electron transfer from metal, followed by protonation by EtOH as shown in Scheme 6.29. 

The mechanism of ester hydrolysis in acid (shown in Mechanism 22.8) is the reverse of the mechanism of ester synthesis from carboxylic acids (Mechanism 22.6). Thus, the mechanism consists of the addition of the nucleophile and the elimination of the leaving group, the two steps common to all nucleophilic acyl substitutions, as well as several proton transfers, because the reaction is acid-catalyzed. 

The mechanism of amide hydrolysis in acid is exactly the same as the mechanism of ester hydrolysis in acid (Section 22.11 A) except that the leaving group is different. 

Early research on the mechanism of ester hydrolysis in aqueous base considered the following one-step Sn2 mechanism as a possibility. 

For esters, all of the steps of the hydrolysis reaction are reversible, and the mechanism of ester formation is the reverse of ester hydrolysis. The course of the reaction is controlled by adjusting the reaction conditions, chiefly the choice of solvent and the concentration of water, to drive the equilibrium in the desired direction. For hydrolysis, the reaction is carried out in an excess of water for ester formation, the reaction is carried out with an excess of the alcohol component under anhydrous conditions. Frequently, an experimental set-up is designed to remove water as it is formed in order to favor ester formation. 

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