Esters hydrolysis and formation

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. 

Ester hydrolysis and formation in strongly acidic media... 

Two other possible reactions of acyl cations, which do not seem to be of general importance under the conditions of ester hydrolysis and formation, are ketene formation... 

Positive evidence that the acyl-oxygen bond is broken on ester hydrolysis and formation is available from experiments using H2,80. Hydrolysis in the enriched solvent results in a net incorporation of, sO into the carboxylic acid produced if acyl-oxygen cleavage occurs, viz-... 

Thus, to define the mechanism of either reaction under given experimental conditions is to define the mechanisms of both, since the transition state or states of lowest energy are necessarily the same in either direction. In practice, however, ester hydrolysis and formation are not carried out under the same conditions. Hydrolysis is carried out in water, but esterification reactions... 

Two types of esterification reaction that can be studied with water as solvent are lactone formation, in which the alcohol is part of the same molecule as the acid, and the lsO-exchange reaction of carboxylic acids, which makes it possible to examine A-2 reactions of carboxylic acids under the conditions used for ester hydrolysis. Work in both these fields confirms the similarities between ester hydrolysis and formation. The hydrolysis and formation of y-butyrolactone have already been discussed (p. 109). We deal here with the lsO-exchange reactions of carboxylic acids. 

Roberts and Urey99 were the first to demonstrate the similarities between ester hydrolysis and formation, and the 180-exchange reaction of carboxylic acids. Not only are all three reactions of the first order in carboxylic acid or ester and the hydronium ion, but the rates of all three are closely similar... 

This would have both a solvent effect and a mass law effect on the rate of ester formation. The error is systematic, since it is most serious for the slower ester formation reactions, and consequently the p value calculated by Jaffe144 from the data of Hartman and Borders142 is not accurate. Later workers allowed for this side-reaction 46 or used aromatic sulphonic acids rather than HC1 as the catalyst145147. However, whatever the exact p values, it is quite clear that the polar effects of substituents on acid-catalyzed ester hydrolysis and formation are small. 

HAMMETT REACTION CONSTANTS, p, FOR ACID-CATALYZED ESTER HYDROLYSIS AND FORMATION... 

The ortho substituent constants, s°, on the other hand, gave no significant correlation with van der Waal s radii. The effects of groups in the ortho position are fully accounted for in terms of o-, and steric effects of groups in the ortho position are constant, negligible, or non-existent251. This result was confirmed by an analysis of the data for acid-catalyzed ester hydrolysis and formation, including those of Tables 20 and 22. 

Another approach, called kinetic resoiution, depends on the different rates of reaction of two enantiomers with a chiral reagent. A very effective form of kinetic resolution uses enzymes as chiral biocatalysts to selectively bring about the reaction of one enantiomer of a racemic mixture (enzymatic resoiution). Lipases, or esterases—enzymes that catalyze ester hydrolysis and formation—have been successfully used in many kinetic resolutions. In a representative procedure, one enantiomer of an ester undergoes hydrolysis and the other is left unchanged. 

Finally, it s useful to remember what we saw in Section 15.3 enzymes can be used to catalyze useful synthetic transformations, and sometimes only limited purification of the enzyme is necessary for it to be effective. In that section, we studied enantioselective ester hydrolysis and formation reactions, such as that in Figure 23.43. However, both isolated enzymes and microorganisms have the capacity to catalyze a wide range of transformations (Figure 23.44). 

JBA van Tol, RMM Stevens, WJ Veldhizen, JA Jongejan, JA Duine. Do organic solvents affect the catal5dic properties of lipase Intrinsic kinetic parameters of lipases in ester hydrolysis and formation in various organic solvents. Biotechnol Bioeng 47 71-81, 1995. 

J. P. Guthrie, Hydration and Dehydration of Phosphoric Acid Derivatives Free Energies of Formation of the Pentacoordinate Intermediates for Phosphate Ester Hydrolysis and of Monomeric Metaphosphate, J. Am. Chem. Soc. 1977, 99, 3391. 

Fig. 3 Mechanisms for enzymatic supramolecular polymerisation (a) Formation of supramolecular assembly via bond cleavage, (b) Formation of supramolecular assemblies via bond formation. Examples are shown of biocatalytic supramolecular polymerisation of aromatic peptide amphiphiles via (i) phosphate ester hydrolysis, (ri) alkyl ester hydrolysis, and (iii) amide condensation or reversed hydrolysis using protease...

With the (S)-PGA enamine-amide route, sitagliptin was prepared in 65% overall yield from 2,4,5-trifluorophenylacetic acid (9) in 4 chemical steps [18]. Two addi-honal crystallization steps are required for enanhomeric purity upgrade and final salt formation. The (S)-PGA enamine-amide hydrogenahon approach eliminated the ester hydrolysis and amide formation steps of the (S)-PGA enamine-ester route by incorporating the newly developed Meldrum s acid chemistry, which enabled direct amidahon with triazole 3. 

Although the quantitative theory of reactions in moderately concentrated solutions of strong acids is unsatisfactory, we do have a good qualitative idea of the processes involved in the acid-catalyzed hydrolysis and formation of esters. Under conditions where the degree of protonation of the substrate is small it is not possible to separate with confidence the factors which affect the solvolytic process and those which affect the preliminary protonation equilibrium. But there have been a number of recent studies of t ie behaviour of carboxylic acids and esters in very strongly acidic media, in. which they are essentially completely protonated. Under these conditions it is possible to observe the behaviour of the protonated species directly. It is appropriate to summarize the results of this research before discussing the reactions under more normal solvolytic conditions. 

The hydrolysis and formation of esters in solutions of strong acids show very varied behaviour, and depend on a rather large number of different factors. Our understanding of the quantitative behaviour of these reactions has become much clearer in recent years, and since an attempt to follow the historical development of the subject might obscure parts of the pattern that has emerged, it seems best to base a discussion on recent results. 

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