Aac2 hydrolysis

If we now extend our consideration of base-catalysed (BAC2), and acid-catalysed (Aac2), hydrolysis to esters in general, including aliphatic ones (RC02Et), we see that there is a close similarity between the transition states (42b or 42a) for the rate-limiting step in each of the two pathways they are both tetrahedral and differ... 

The effects of added salts are shown in Fig. 8. Sodium chloride has a small positive effect on the hydrolysis rate, and sodium chloride and sodium perchlorate have a similar, rather larger, effect on the rate of lactone formation. This is the expected result, for many salts increase the protonating power of the medium as measured by Hammett s acidity function116, and thus assist acid-catalyzed reactions. Sodium perchlorate, unusually, has a small negative effect on the hydrolysis rate. Qualitatively similar results have been found by Bunton et al,56, who studied the effects of added salts on the acid-catalyzed hydrolysis of ethyl acetate. Added lithium and sodium chloride assist the Aac2 hydrolysis of ethyl acetate, but the perchlorates have essentially no effect. In each case the effect is a little more positive than for y-butyrolactone hydrolysis, and, in particular, chloride anions appear to assist Aac2 hydrolysis more effectively than do the perchlorates. 

The most likely transition state for the AAc2 hydrolysis of these esters is the model given below, which corresponds to nucleophilic attack of water onto the carbonyl carbon of the carbonyl oxygen protonated ester, viz. 

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. ... 

For acid catalysis, matters are less clear. The reaction is generally second order, and it is known that amides are primarily protonated on the oxygen (Chapter 8, Ref. 24). Because of these facts it has been generally agreed that most acid-catalyzed amide hydrolysis takes place by the Aac2 mechanism. 

That the major factor responsible for this shift in reaction pathway is indeed a steric one is demonstrated by the observation that the acids (191) and (192), and their simple esters, undergo ready esterification/hydrolysis by the normal Aac2 mode ... 

Considering first the simpler of the two cases, the straight line for the methyl esters (34a) which has a p value of -3-25. From this p value it is apparent that this reaction cannot be proceeding via the normal (Aac2) pathway (p. 241) for acid-catalysed ester hydrolysis which, as we know (reaction 6, p. 364), has a p value of +0-03. That value refers, however, to hydrolysis being carried out with dilute sulphuric acid, while here 99-9% sulphuric acid is being used one... 

T.S. for base-catalysed T.S. for acid-catalysed hydrolysis (BAC2) hydrolysis (Aac2)... 

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... 

Figure 2.3 Aac2 mechanism for esterification/hydrolysis and transesterification/ glycolysis...

Esterification, hydrolysis, transesterification and glycolysis have equilibrium constants close to unity and proceed via an AAc2 mechanism (Figure 2.3) [9, 18],... 

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... 

These considerations can be formulated by schemes (e)—(g) below (R1 = H or alkyl). Scheme (e), in which the acid (ester) is protonated and alcohol reacts in non-adsorbed state, corresponds to the mechanisms Aac1 or Aac2 proposed for homogeneous esterification and hydrolysis with ion exchanger catalysts, the mechanism (e) was assumed to be operating in the liquid phase esterification of salicyclic acid with methanol [449] and in the transesterification of ethyl acetate with the same alcohol in dioxan 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-... 

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