Esters Aac2 mechanism

The acid-catalyzed hydrolysis of enol esters (RCOOCR =CR) can take place either by the normal Aac2 mechanism or by a mechanism involving initial protonation on the double-bond carbon, similar to the mechanism for the hydrolysis of enol ethers given in 10-6, ° depending on reaction conditions. In either case, the products are the carboxylic acid RCOOH and the aldehyde or ketone R2" CHCOR. ... 

Further evidence for the Aa11 mechanism was obtained from a solvent kinetic isotope study. The theoretical kinetic isotope effects for intermediates in the three reaction pathways as derived from fractionation factors are indicated in parentheses in Scheme 6.143,144 For the Aa11 mechanism (pathway (iii)) a solvent KIE (/ch2o A d2o) between 0.48 and 0.33 is predicted while both bimolecular processes (pathways (i) and (ii)) would have greater values of between 0.48 and 0.69. Acid-catalysed hydrolysis of ethylene oxide derivatives and acetals, which follow an A1 mechanism, display KIEs in the region of 0.5 or less while normal acid-catalysed ester hydrolyses (AAc2 mechanism) have values between 0.6 and 0.7.145,146... 

Further evidence for this mechanism is that a small but detectable amount of 180 exchange (see p. 332) has been found in the acid-catalyzed hydrolysis of benzamide.551 (180 exchange has also been detected for the base-catalyzed process,562 in accord with the Bac2 mechanism). Kinetic data have shown that three molecules of water are involved in the ratedetermining step,563 suggesting that, as in the Aac2 mechanism for ester hydrolysis (0-10), additional water molecules take part in a process such as... 

With solutions of low acidity the increase in the concentration of the conjugate acid of the ester outweighs the decrease in activity of water, and the rate of hydrolysis by the A2 mechanism increases with increasing acid concentration, as expected. Most esters are, in fact, hydrolyzed by the Aac2 mechanism in less concentrated solutions of strong acids all the esters in Fig. 1, for ex-... 

In fact this pathway cannot be a great deal more favourable than the normal ester hydrolysis (Aac2) mechanism since this appears in the case of methoxy-methyl formate80, is dominant in the hydrolysis of /3-chloroethoxy methyl acetate81, CICH2CH2OCH2OCOCH3, and is apparently the sole important mechanism for the hydrolysis of methylene diacetate, CH ,COO CH2-OCOCH,82. 

The two unimolecular mechanisms for acid-catalyzed ester hycrolysis described above represent exceptional behaviour. They are generally observed only with compounds with narrowly defined structural characteristics, or under extreme conditions. The vast majority of esters are hydrolyzed under the vast majority of acidic conditions by the Aac2 mechanism, and since ester hydrolysis has been a traditional proving ground for theories relating structure and reactivity, a wealth of data is available. Yet the detailed mechanism of the reaction is still in dispute. 

A rather similar result has been obtained much more recently by Sadek et a/.108. These authors carried out a detailed investigation of the hydrolysis of benzyl acetate in aqueous dioxan, varying the solvent composition, and also the temperature (from 25 to 45°C). In the low-acidity region used (0.05 M HC1) the ester is hydrolyzed by the Aac2 mechanism, and the solvent effects are probably typical. The rate of hydrolysis decreases steadily as the proportion of dioxan in the medium is increased, as a result of a steady increase in AH, which is only partially offset by an increasingly favourable entropy of activation. However, the increase in AS1 eventually levels out at about 70% w/w dioxan, as illustrated by the data for 30°C ... 

If it is assumed that ester hydrolysis by the AAc2 mechanism involves fast pre-equilibrium protonation of the substrate, followed by rate-determining attack of water on the conjugate acid of the ester, the mechanism can be written as... 

The Aac2 mechanism (Figure 6.22) of ester hydrolysis represents an SN reaction at the carboxyl carbon, which follows the general mechanism of Figure 6.5. Acid-catalyzed hydrolyses of carboxyhc esters that are derived from primary or from secondary alcohols take place according to the Aac2 mechanism. The reverse reactions of these hydrolyses follow the same mechanism, namely, the acid-catalyzed esterifications of carboxylic acids with alcohols. In the esterifications, the same intermediates are formed as during hydrolysis, but in the opposite order. 

Fig. 6.19. Aac2 mechanism of the acid-catalyzed hydrolysis of carboxylic esters (read from left to right) Aac2 mechanism of the Fischer esterification of carboxylic acids (read from right to left). H+ means migration of a proton.

Unlike acetals, for which one mechanism seems to describe most of the hydrolysis reactions that have been studied, the mechanism of acid-catalyzed hydrolysis of an ester depends on the structure of the ester and on the reaction conditions. For example, Yates concluded that hydrolysis of primary esters occurs by the Aac2 mechanism below 90% H2SO4 but changes to the AacI mechanism in solutions with higher concentrations of sulfuric acid (and... 

Hydrolyses with maximum curve (type I and II behavior) are easily explained by the Aac2 mechanism. The initial rate increase is attributed to the increasing concentration of the protonated ester. The rate then decreases since concentration of water required for the hydrolysis step decreases rapidly with increasing acid concentration (Scheme 8). The final rate increase suggests a transition to the A1 process (Aac 1 for type I esters and Aal 1 for type II esters). There is also a change in the mechanism for type III esters. Since the participation of vinyl and phenyl cations are unlikely, a change to the Aac 1 mechanism was suggested. Finally, the hydrolysis pathway for type IV esters is the AalI mechanism. 

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