Hydrolysis of carboxylic esters

Hydrolysis of carboxylic esters to a carboxylic acid and an alcohol occurs in an alkaline or an acid medium  

Acid hydrolysis requires only catalytic amounts of an acid however, for alkaline hydrolysis (saponification) an equimolar amount of alkali is necessary since this is not merely a catalyst but also acts by withdrawing the acid as salt from the equilibrium mixture.47 48 

The rate of hydrolysis of carboxylic esters can be increased by raising the temperature. It is also advantageous to remove the alcohol produced by continuous distillation. Acid hydrolysis is dependent on the hydrogen ion concentration it is usually considerably slower than alkaline hydrolysis of esters. 

Hydrolysis by alkali The usual reagent is a solution of sodium hydroxide or potassium hydroxide in water or an alcohol (methanol, ethanol, or diethyleneglycol). Milder reagents are solutions of barium or calcium hydroxide. If fission of an ester gives products that are sensitive to strong alkali, it can often be effected with advantage by a solution of sodium carbonate, sodium hydrogen carbonate, or sodium methoxide.52 For hydrolysis of particularly stable esters, such as n,n -disubstituted aromatic carboxylic esters, it is sometimes necessary to use an alkali melt. 

The concentration of the alkali and the temperature to be used depend on the ease of hydrolysis of the ester and on the stability of the products. 

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Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

Taft, following Ingold," assumed that for the hydrolysis of carboxylic esters, steric, and resonance effects will be the same whether the hydrolysis is catalyzed by acid or base (see the discussion of ester-hydrolysis mechanisms. Reaction 10-10). Rate differences would therefore be caused only by the field effects of R and R in RCOOR. This is presumably a good system to use for this purpose because the transition state for acid-catalyzed hydrolysis (7) has a greater positive charge (and is hence destabilized by —I and stabilized by +1 substituents) than the starting ester. 

Of fhe eight mechanisms, seven have actually been observed in hydrolysis of carboxylic esters. The one that has not been observed is the BacI mechanism. 

Buchwald P. Structure-metabolism relationships steric effects and the enzymatic hydrolysis of carboxylic esters. Mini Rev Med Chem 2001 1 101-11. 

Just as intramolecular catalysis has been observed in the hydrolysis of carboxylate esters, a variety of neighbouring groups can participate in the hydrolysis of phosphates. The alkaline hydrolysis of dimethyl phosphoacetoin [47] has found to be ca. 2 x 106 times faster in water at 25°C than that of... 

Heymann, E. (1982) Hydrolysis of carboxylic esters and amides. In W.B. Jakoby, J.R. Bend and J. Caldwell (Eds.), Metabolic Basis Detoxification, Academic Press, New York, pp. 229-245. 

The Mechanism of, and Constitutional Factors Controlling, the Hydrolysis of Carboxylic Esters. Pt. I. The Constitutional Significance of Hydrolytic Stability Maxima," JCS (1930) 10321057, on 1037. 

E. Heymann, Hydrolysis of Carboxylic Esters and Amides in Metabolic Basis of Detoxication , Eds. W. B. Jakoby, J. R. Bend, J. Caldwell, Academic Press, New York, 1982, p. 229-245. 

The occurrence of isotopic exchange of between water and carbonyl compounds has been observed to take place slowly with acetone (Cohn and Urey, 1938) and much more rapidly with acetaldehyde (Herbert and Lauder, 1938). This gives qualitative evidence for reversible hydration (since no other reasonable mechanism exists for isotopic exchange), but gives no quantitative information about the equilibrium position. Similarly, the fact that exchange occurs in the unhydrolysed ester during the hydrolysis of carboxylic esters (Bender, 1951) shows that the species RC(0H)20R is a stable intermediate rather than a transition state. 

Torrents, A. Stone, A.T (1994) Oxide surface-catalysed hydrolysis of carboxylate esters and phosphorothioate esters. Soil Sd. Soc. Am. J. 58 738-745... 

The possibility that the reactions of derivatives of carboxylic acids might pass through tetrahedral intermediates (l) has long been considered (Lowry, 1926). In their important paper in which they classified the mechanisms of hydrolysis of carboxylic esters Day and Ingold (1941) wrote bimolecular... 

In discussing Reaction (F), we remarked that other anions are observed to compete with OH " in the Stern layer. This sort of electrolyte inhibition is widely observed, and the dependence of the inhibition on both the size and charge of the ions generally corresponds to expectations. For example, in the base-catalyzed hydrolysis of carboxylic esters in the cationic micelles, anions inhibit the reaction in the order N03 > Br " > Cl > F. For acid-catalyzed ester... 

Hydrolysis of carboxylic esters 0-17 Transetherification 0-18 Payne rearrangement 0-23 Transesterification 0-55 Ammonolysis of carboxylic esters 0-68 Cleavage of ethers with concentrated acids... 

Hydrolysis of carboxylic esters 0-11 Hydrolysis of amides 0-70 Cleavage of carboxylic esters with Lil... 

Since in numerous cases of hydrolysis of nitric esters the presence of a large amount of nitrate ion has been established, which could be liberated only by rupture of the C—0 bond, the factors that influence the direction of this process should be discussed. Several investigations have thrown light on this problem, which is more complicated than with carboxylic esters, since during the hydrolysis of the latter compounds whether in acid or in alkaline medium only rupture of the ester bond can take place. This has been established in various ways including the use of water containing an 180-isotope. In general the hydrolysis of carboxylic esters can be defined by the equation ... 

Fig. 6.3. Alkaline hydrolysis of carboxylic esters according to the mechanism of Figure 6.2 proof of the reversibility of the formation of the tetrahedral intermediate. In the alkaline hydrolysis of ethyl pora-methylbenzoate in H20, for example, the ratio kretlo/kelj is at least 0.13 (but certainly not much more).

The hydrolysis of carboxylic esters can in principle take place either as carboxyl-O cleavage, i.e., as an SN reaction at the carboxyl carbon—... 

Fig. 6. 22. Aa[2 mechanism of the acid-catalyzed hydrolysis of carboxylic esters (read from left to right) Aa[2 mechanism of the Fischer esterification of carboxylic acids (read from right to left). H means migration of a proton.

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