Acid-catalyzed ester hydrolysis correlation

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. 

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).

Because the ester hydrolysis leads to a change in acidity, as in hydrolytic lipase-or esterase-catalyzed kinetic resolution, an appropriate pH indicator can be used for quantification [14,15]). In an optimized version (Kazlauskas test) [15], a linear correlation between the amount of acid generated and the degree of protonation of the indicator was ensured by using a buffer (e. g., iV,iV-bis(2-hydroxyethyl)-2-(aminoethanesulfonic acid) (= BES), and a pH indicator (e. g., / -nitrophenol) having the same pKa value. The advantage of this system relates to the fact that p-nitrophenol esters are not necessary, i. e., normal substrates such as methyl esters 10 can be used. 

In principle, extrathermodynamic relationships that deviate from the simple Hammett equation (equation 8) can be treated by equation 14. The major problem is the determination of the different sets of o s, (e.g., set and 0 set) in a way that will indeed reflect their relation to independent properties. An example of such a procedure is the separation of polar and steric effects (10). The need for such a separation arose when a nearly complete lack of correlation was observed between substituent effects represented by the Hammet a constants and the rates for alkaline hydrolysis of aliphatic systems (12). Inspection of the structures indicated that the proximity of the substituents to the reaction site was a common feature. The steric interaction between R and X had to be considered separately from the electronic effects. Polar substituent constants were thus defined as the difference between the rate constants of base and acid catalyzed hydrolysis of esters. From the structural similarity of the transition states for these reactions (equation 15) it was assumed that the difference in their charge reflects only the polar effect of the substituent... 

Protein Hydrolysates. Instead of ethyl hippurate, a peptic hydrolysate of ovalbumin was used as substrate for the resynthesis reaction (64). This substrate (300 mg) was dissolved in water, adjusted to pH 6.0 with NaOH and to 0.9 ml with additional water. An amino acid ester was added to produce a 22.2mM solution and the mixture preincubated at 37°C for 15 min. Papain (3 mg), dissolved in 0.1M L-cysteine (0.1 ml), was combined with the above-mentioned preincubation mixture and incubation carried out at 37°C. After 2 hr, 0.1N NaOH (10 ml) was added to stop the enzymatic reaction and the resulting solution allowed to stand for 3 hr to hydrolyze completely the remaining amino acid ester as well as the ester group from the peptide product. The free amino acid produced from the base-catalyzed hydrolysis of the amino acid ester was determined with an amino acid analyzer. The amount of the amino acid incorporated was obtained by subtracting the determined value from the initial concentration of amino acid ester. The data obtained with the same L-amino acid esters as used in the model experiment (above) are plotted along the ordinate of Figure 3. An excellent correlation is found between the data from the model experiment and those from this experiment using a protein hydrolysate. In Table III data are shown for the extent of covalent incorporation after 2 hr of various amino acid ethyl esters into the protein hydrolysate. There is a close relationship between... 

Taft equation. Taft (1956) has extended the Hammett-type correlation to aliphatic systems. Because steric effects of substituents in aliphatic systems cannot be ignored as they were for m- and / -substituted benzene compounds, Taft recognized the need to develop separate terms for the polar and steric effects for substituent constants. Based on the observation that the acid-catalyzed hydrolysis of meta- and para-substituted benzoic acid esters are only slightly affected by the electronic nature of the substituent group (p values are near 0), Taft concluded that the acid-catalyzed hydrolysis of aliphatic esters would also be insensitive to polar effects of substituent groups. Any effect on rate due to substituent groups could therefore be attributed to steric effects. Taft defined a steric substituent constant, E, by ... 

The 8-parameter was used with good results in structure-activity correlations for modeling the acid-catalyzed carboxylic acid esterification and ester hydrolysis, and bimolecular substitution reactions (Chiriac et al. 1996). 

The question about the relation between the reactivity of reactants and their structure is one of the fundamental problems of chemistry. This problem as one of the main directions of chemical kinetics was formulated in the general form about 100 years ago by N.A. Menshutkin in his works on hydrolysis of esters. One of the most important directions in this area is correlation equations relating the reaction rate constant to thermodynamic and structural parameters of reactants. The first correlation was proposed by Ch. Taylor (1914) who noticed a proportionality between the ionization rate constant of the catalyst and rate constant of the catalyzed reaction. The systematic work on correlations in chemical kinetics started from the works of J. BrSnsted and K. Pedersen who, using the results of their study of the reactions catalyzed by acids ( ha) and bases ( a), proposed the equations relating the rate constants of catalytic reactions to the dissociation constants of acids ituA (1924)... 

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