Acid-catalyzed ester hydrolysis rate constants

Acid-Catalyzed Hydrolysis. In acid-catalyzed ester hydrolysis the species that undergoes the rate-determining step is the protonated ester (Fig. 13.10). When the molecule is in this protonated form, the enhanced depletion of electrons near the central carbon promotes the approach of an electron-rich oxygen of a water molecule. Hence, the hydrolysis rate depends on the fraction of compound molecules that are protonated. This fraction, in turn, depends on how strong a base the ester function is. If we define an acidity constant (see Chapter 8) for the protonated species... 

For a given pesticide which undergoes hydrolysis, any or all of these hydrolytic pathways may be relevant at various pH s. Organophosphorothioates, for example, have measurable neutral and alkaline hydrolysis rate constants (7). Esters of 2,4-dichlorophenoxyacetic acid (2,4-D), on the other hand, hydrolyze by acid and alkaline catalyzed reactions, but have extremely small neutral hydrolysis rate constants ( ). Thus, any study of the hydrolysis of sorbed pesticides must be prefaced by an understanding of the hydrolytic behavior of individual pesticides in aqueous solution. 

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. 

Acid catalysis—hydrolysis. Several series of alkylsilane esters were studied to determine the effect of silane structure on the hydronium ion catalyzed hydrolysis reaction. The hydronium ion catalyzed hydrolysis rate constants for a series of alkyl tris-(2-methoxyethoxy)silanes in aqueous solution were used to define the modified Taft equation log(A /Ah ) = 0.39a + 1.06ES, where Ho is the rate of hydrolysis for methyl tris-2-(methoxyethoxy)silane [42], The hydronium ion catalyzed hydrolysis rate constants and the reaction half-lives are reported in Table 2. In a similar manner, the hydronium ion catalyzed hydrolysis rate constants for a series of trialkylalkoxysilanes in 55% aqueous acetone were used to obtain the modified Taft equation log(/cH//cHo) = -0.37 a + 2.48 E where kHo is the rate of hydrolysis for trimethylalkoxy-silane. 

Aqueous hydrolysis rate constants for esters, carbamates, epoxides, halomethanes, and selected alkyl halides. Acid- and base-catalyzed rate constants are estimated, but not neutral hydrolysis rate constants. 

The effect of increasing the hydrocarbon chain length from methyl to octadecyl on the acid catalyzed, neutral, and base catalyzed hydrolysis of n-alkyl sulfate esters has been examined (Kurz, 1962). The rate constants for the neutral hydrolysis decrease smoothly from methyl to dodecyl sulfate and hence are unaffected by micellization of the longer chain esters. The rate constants for the acid-catalyzed hydrolysis, however, are relatively constant for the non-micellar ester but increase dramatically with micelle formation (Table 7). Conversely, the hydroxide... 

Bransted LFER. Bronsted and Pederson (1923) were the first to describe a relationship between rates and equilibria for a series of compounds. They found that log/cB for base-catalyzed decomposition of nitramide, H2N202, varies linearly with log/CHB+, the acidity constant of the conjugate acid of the catalyst. Rate constants for many other acid- or base-catalyzed reactions (including the hydrolysis of amides, esters, carbamates, and organophosphates, and dissociation of acids and metal-ion complexes) are log-log related to the acid (or base) dissociation constant of the catalyst and follow either of the equations... 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

This property of organophosphate esters may be of environmental importance since phosphoric acid diesters are much more soluble and very little is known concerning the environmental toxicity of these compounds. The available data do not provide sufficient descriptions of the experimental methods to determine if the rates are reliable (Barnard et al. 1961 Ciba-Geigy 1984e, 1986 Howard and Deo 1979 Mayer et al. 1981 Wolfe 1980). The majority of reports provide only a minimum of information and exclude important facts such as the duration of the experiments and the concentration of buffers. Despite the lack of experimental detail, published rate constants for base-catalyzed hydrolysis appear to be reasonably consistent and suggest that the hydrolytic half-life of triphenyl phosphate will vary from... 

Quantitative measurements of simple and enzyme-catalyzed reaction rates were under way by the 1850s. In that year Wilhelmy derived first order equations for acid-catalyzed hydrolysis of sucrose which he could follow by the inversion of rotation of plane polarized light. Berthellot (1862) derived second-order equations for the rates of ester formation and, shortly after, Harcourt observed that rates of reaction doubled for each 10 °C rise in temperature. Guldberg and Waage (1864-67) demonstrated that the equilibrium of the reaction was affected by the concentration ) of the reacting substance(s). By 1877 Arrhenius had derived the definition of the equilbrium constant for a reaction from the rate constants of the forward and backward reactions. Ostwald in 1884 showed that sucrose and ester hydrolyses were affected by H+ concentration (pH). 

Similarly, chemical hydrolysis of a number of a-amino acyl prodrugs of metronidazole (8.100, R=H see Sect. 8.5.4) was compared to the serum-catalyzed reaction [135][136]. The amino acids used for esterification included alanine, glycine, isoleucine, leucine, lysine, phenylalanine, and valine. Under physiological conditions of pH and temperature, ty2 values for hydrolysis in human serum ranged from 4.5 min for the Phe ester to 96 h for the lie ester. A good linear relationship was established between the log of the rate constant of enzymatic hydrolysis and the log of the rate constant of HO-cata-... 

The enhanced reactivity in the cupric ion-catalyzed hydrolysis cannot be due solely to the electrostatic effect of an attack of hydroxyl ion on a positively charged a -amino ester, since the introduction of a positive charge, two atoms from the carbonyl group of an ester, increases the rate constant of alkaline hydrolysis by a factor of 103 (10), whereas there is a difference of approximately 106 between the cupric ion-catalyzed and the alkaline hydrolyses of DL-phenylalanine ethyl ester. The effective charge on the cupric ion-glycine (buffer)-ester complex is +1, so that the factor of 106 cannot be explained by an increase in charge over that present in the case of betaine. Furthermore, the reaction cannot be due to attack by a water molecule on a positively charged a-amino acid ester, since the rate constant of the acidic hydrolysis of phenylalanine ethyl ester is very small. It thus seems... 

Table 12.1 Reaction Rate Constants for the Base-Catalyzed Hydrolysis of Benzoic Acid Ethyl Ester (Ethyl Benzoate) in Various Organic Solvent-Water Mixturesa...

Figure 13.15 Effects of substituents on the base-catalyzed hydrolysis of benzoic acid ethyl esters in ethanoliwater (85 15) at 25°C. Relative reaction rates are correlated with Hammet Oj constants (data from Tinsley, 1979).

In fact p for the acid-catalyzed hydrolysis and formation of benzoate esters is small, and since the fit to the Hammett equation is characteristically rather poor for these reactions, p is often taken as zero. Some typical values are listed in Table 16. Too much weight should not be attached to the absolute values of the reaction constants given in the table. The data do not fit the Hammett equation accurately, and it is known that much of the earlier work was subject to considerable error, because no allowance was made for the slow reaction of the catalyst with the solvent. This could affect the observed rate coefficients in three ways—by reducing the catalyst concentration, by decreasing the acid content as measured by titration, and by producing water, e.g. 

The kinetic order in water for the spontaneous hydrolysis reaction, n, and the hydronium ion catalyzed reaction, m, varies depending on the structure of the silane ester and the solvent conditions [36, 40]. The difficulty in determining the kinetic order of water in aqueous-organic solvents arises from the observation that as the concentration of water is varied, the polarity of the solvent and the activity of the acid change [40], A plot of the logarithm of the rate constant vs. the logarithm of water concentration often does not yield a straight line. These... 

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