Carboxylic esters, hydrolysis rates

Because of the relative simplicity of carboxylic ester hydrolysis, in general, and that of base catalyzed ester hydrolysis, in particular, these reactions have served well as model systems in investigations of micellar effects on reaction rates and activation parameters. In addition, the prevalence in biological systems of carboxylic ester hydrolyses catalyzed by nucleophiles and by enzymes renders the investigation of micelle-catalyzed ester hydrolyses of obvious importance. 

Again by analogy with peptide hydrolysis, metalloenzymes catalyzing ester hydrolysis may take advantage of additional chemical features provided by amino-acid residues present in the active-site cavity. This situation occurs with car-boxypeptidase, " which shows esterase activity in vitro. Although the rate-limiting steps for carboxylic esters and peptides may differ, several features, such as the pH dependences of cat and and the presence of two spectroscopically observable intermediates, point to substantially similar mechanisms. On the other hand, carboxylic ester hydrolysis catalyzed by carbonic anhydrase seems to rely on fewer additional features of the active-site cavity, perhaps only on the presence of a metal-coordinated hydroxide that can perform the nucleophilic attack on the carbonyl carbon atom." ... 

Complexatlon with Ni to form 17 gives a 56x increase in the ester-hydrolysis rate, while ionization of the sallcyl carboxyl produces a further 1.7x increase, leading to the postulate of biTfunctlonal (carboxylate-metal Ion) catalysis. The carboxylate effect is in the wrong direction for... 

The first was proposed by Iraoto and Otsuji (511) and Otsuji et al (512) and concerned the pK of substituted 2-, 4-, and 5-carboxylic acids and the alkaline hydrolysis rate k of their respective ethyl esters (259, 260, and 261, where Y = Et). When Hammett cr , values were used for... 

Table 7-17. Relative Rates of Intramolecular Catalysis of Ester Hydrolysis by Carboxylate Groups...

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. 

The intermediates 74 and 76 can now lose OR to give the acid (not shown in the equations given), or they can lose OH to regenerate the carboxylic ester. If 74 goes back to ester, the ester will still be labeled, but if 76 reverts to ester, the 0 will be lost. A test of the two possible mechanisms is to stop the reaction before completion and to analyze the recovered ester for 0. This is just what was done by Bender, who found that in alkaline hydrolysis of methyl, ethyl, and isopropyl benzoates, the esters had lost 0. A similar experiment carried out for acid-Catalyzed hydrolysis of ethyl benzoate showed that here too the ester lost However, alkaline hydrolysis of substimted benzyl benzoates showed no loss. This result does not necessarily mean that no tetrahedral intermediate is involved in this case. If 74 and 76 do not revert to ester, but go entirely to acid, no loss will be found even with a tetrahedral intermediate. In the case of benzyl benzoates this may very well be happening, because formation of the acid relieves steric strain. Another possibility is that 74 loses OR before it can become protonated to 75. Even the experiments that do show loss do not prove the existence of the tetrahedral intermediate, since it is possible that is lost by some independent process not leading to ester hydrolysis. To deal with this possibility. Bender and Heck measured the rate of loss in the hydrolysis of ethyl trifluorothioloacetate- 0 ... 

The rate of appearance of p-nitrophenolate ion from p-nitrophenyl methylphosphonate (7), an anionic substrate, is moderately accelerated in the presence of cycloheptaamylose (Brass and Bender, 1972). The kinetics and pH dependence of the reaction are consistent with nucleophilic displacement of p-nitrophenolate ion by an alkoxide ion derived from a cycloheptaamylose hydroxyl group to form, presumably, a phosphonylated cycloheptaamylose. At 60.9° and pH 10, the cycloheptaamylose-induced rate acceleration is approximately five. Interestingly, the rate of hydrolysis of m-nitrophenyl methylphosphonate is not affected by cycloheptaamylose. Hence, in contrast to carboxylate esters, the specificity of cycloheptaamylose toward these phosphonate esters is reversed. As noted by Brass and Bender (1972), the low reactivity of the meta-isomer may, in this case, be determined by a disadvantageous location of the center of negative charge of this substrate near the potentially anionic cycloheptaamylose secondary hydroxyl groups. 

Mineral surfaces may accelerate the rate of ester hydrolysis (Stone, 1989 Hoffmann, 1990 Torrents and Stone, 1991). One plausible scheme for this heterogeneous catalysis assumes a nucleophilic addition of the ester to the surface functional group, e.g., in case of a carboxylic acid ester... 

It has been known that a micelle of l-hydroxyethyl-2-dimethylhexadecyl-ammonium bromide [21] exhibits high nucleophilic reactivity towards phosphate esters, carboxylic esters, 2,4-dinitrohalobenzene, etc. (Bunton et al., 1970 Bunton and Minch, 1970 Bunton and Ionescu, 1973 Martinek et al., 1975b Bunton and Diaz, 1976 Moss et al., 1975 Bunton and McAneny, 1977 Pillersdorf and Katzhendler, 1979). In the hydrolysis of PNPA, for example, the apparent rate constant for [21] is greater by a factor of 14 than that for choline (CH3 instead of C16Hjj in [21]) (Moss et al., 1975). However,... 

Base-Catalyzed Hydrolysis. Let us now look at the reaction of a carboxylic ester with OH", that is, the base-catalyzed hydrolysis. The reaction scheme for the most common reaction mechanism is given in Fig. 13.11. As indicated in reaction step 2, in contrast to the acid-catalyzed reaction (Fig. 13.10), the breakdown of the tetrahedral intermediate, I, may be kinetically important. Thus we write for the overall reaction rate ... 

When comparing the hydrolysis rate constants of a series of carboxylic acid esters (Table 13.8), it can be seen that the values for the acid-catalyzed reactions are all of the same magnitude, whereas the rate constants for the base-catalyzed reactions vary by several orders of magnitude. Explain these findings. 

The rate of hydrolysis of a carboxylic ester in strong sulphuric acid generally shows one of the three types of dependence on acid concentration illustrated in Fig. 1. The simplest behaviour, a continuous increase in hydrolysis rate with increasing acid concentration, is shown by esters of tertiary alcohols, which are hydrolyzed very rapidly even in moderately concentrated acid, and by phenol esters, which are somewhat less reactive, but are hydrolyzed much faster than esters of simple primary and secondary alcohols with above about 60% H2S04. Substituted phenyl acetates behave very much like the parent compound, the p-chlorophenyl ester being hydrolyzed at almost the same rate as the unsubstituted compound, while p-nitrophenyl acetate is somewhat less reactive at low acid concentrations, but more reactive in above 70% sulphuric acid. 

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... 

Succinate esters serve as examples of derivatives that exhibit less than optimal pH-hydrolysis rate behavior owing to their increased reactivity in water as a result of intramolecular catalysis of hydrolysis by the terminal carboxylic acid functionality (Anderson and Taphouse, 1981 Anderson etal., 1984 Damen etal., 2000). Since intramolecular catalytic effects are quite sensitive to geometric factors and distances separating the interactive groups (Anderson and Conradi, 1987), intramolecular catalysis by a terminal ionizable group should be easily controlled by varying the alkyl chain length. 

Log of the alkaline hydrolysis rate constant vs. difference in carbon-oxygen stretching frequency for 12 carboxylic acid esters. 

Estimation methods for the hydrolysis rates of several types of carboxylic acid esters, carbamates, aromatic nitriles, and phosphoric acid esters have been reported. Hydrolysis rates are subject to substituent effects, and consequently LFERs, as represented by Hammett or Taft correlations, have been applied to their estimations. Reviews (e.g., Harris, 1990 Peijnenburg, 1991 Nendza, 1998) reveal that QSARs are available only for a few compound classes and are based mostly on... 

To understand the role of metal ions in hydrolysis reactions, it is useful to first consider the background hydrolysis reactions. Table 6.1 lists the second-order rate constants for hydroxide-catalyzed hydrolysis of various substrates. The reactivity of methyl acetate (first entry in Table 6.1) [16] is comparable to those of other unactivated esters found in nature (e.g. acetyl choline and carboxyl esters in phospholipids). The reactivity of N-methylacetamide (second entry in Table 6.1) [17] is comparable to those of typical peptides (1.1 x 10 6 m-1 s 1) [18] and that of dimethyl phosphate (P-O bond... 

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