Phenyl acetate hydrolysis

Phenyl acetates, hydrolysis of, and derivatives, catalytic action of cycloamyloses on, 23 222-228, 254 Phenylacetylene hydration, 41 155... 

First-order and second-order rate constants have different dimensions and cannot be directly compared, so the following interpretation is made. The ratio ki k,ma has the units mole per liter and is the molar concentration of reagent Y in Eq. (7-72) that would be required for the intermolecular reaction to proceed (under pseudo-first-order conditions) as fast as the intramolecular reaction. This ratio is called the effective molarity EM), thus EM = kimnJk,Ma- An example is the nucleophilic catalysis of phenyl acetate hydrolysis by tertiary amines, which has been studied as both an intermolecular and an intramolecular process. ... 

Figure 7.3. Transition state analogue hapten used for the generation of catalytic antibodies for phenyl acetate hydrolysis.

The work of Kawanami et al., who produced a MIP to catalyse p-nitro-phenyl acetate hydrolysis, serves to illustrate the methodology (Fig. 6) [124]. p-Nitrophenyl phosphate, employed as a template molecule, was observed to form an insoluble complex when mixed in solution with a 10-fold excess of the chosen functional monomer, 1-vinylimidazole this was then copolymerised with a 20-fold excess of divinylbenzene. Following polymerisation. 

Nucleophilic catalysis is catalysis by a general base (electron-pair donor) acting by donating its electron pair to an atom (usually carbon) other than hydrogen. Nucleophilic catalysis is exemplified by the imidazole-catalyzed hydrolysis of a phenyl acetate. (The tetrahedral intermediates are not shown.)... 

We should distinguish between the phrases nucleophilic attack and nucleophilic catalysis. Nucleophilic attack means the bond-forming approach by an electron pair of the nucleophile to an electron-deficient site on the substrate. In nucleophilic catalysis this results in an increase in the rate of reaction relative to the rate in the absence of the catalyst. However, nucleophilic attack may not result in catalysis. Thus, if methylamine is reacted with a phenyl acetate, the reaction observed is amide formation, not hydrolysis, because the product of the nucleophilic attack is more stable than is the ester to hydrolysis. 

Nishioka and Fujita78) have also determined the Kd values fora- and (S-cyclodextrin complexes with p- and/or m-substituted phenyl acetates through kinetic investigations on the alkaline hydrolysis of the complexes. The Kd values obtained were analyzed in the same manner as those for cyclodextrin-phenol complexes to give the Kd(X) values (Table 5). The quantitative structure-activity relationships were formulated as Eqs. 30 to 32 ... 

Quantitative structure-reactivity analysis is one of the most powerful tools for elucidating the mechanisms of organic reactions. In the earliest study, Van Etten et al. 71) analyzed the pseudo-first-order rate constants for the alkaline hydrolysis of a variety of substituted phenyl acetates in the absence and in the presence of cyclodextrin. The... 

Michaelis-Menten kinetics. Consider the hydrolysis of phenyl acetate catalyzed by acetyl cholinesterase,... 

There have been a number of hydrolysis studies. The mechanism of alkaline hydrolysis of phenyl dimethylthiophosphinate has been compared to that of phenyl acetate.27 Evidence for the formation of five coordinate oxyphosphorane intermediates in the alkaline hydrolysis of aryl diphenylthiophosphinates is based on the lack of development of negative charge on the leaving group in the transition state.279... 

Phosphate ester crystal structures have been determined of zinc 1,5,9-triazacyclononane including an interesting structure containing an oligophosphate bridged zinc unit.450 The zinc complex of 1,5,9-triazacyclododecane was studied as a hydrolysis catalyst for substituted phenyl acetates.451 Kinetic analysis suggested that hydrolysis occurs by a mechanism involving hydroxide attack of a metal-bound carbonyl. 

Figure 1. Hydrolysis pH-rate profiles of phenyl acetate (lower) and a substituted 2-phenyl-l,3-dioxane (HND). Phenyl acetate profile constructed from data of Mabey and Mill (32), HND profile from data of Bender and Silver (33). Phenyl acetate reacts via specific-acid catalyzed, neutral, and base-catalyzed transformation pathways. The pseudo-first-order rate constant is given by Kobs = K(h+) [H+] + Kn + K(qh-) [0H—]. HND hydrolyzes only via an acid-catalyzed pathway the phenolate anion is some 867 times more reactive than its conjugate acid.

As a simple model for the enzyme penicillinase, Tutt and Schwartz (1970, 1971) investigated the effect of cycloheptaamylose on the hydrolysis of a series of penicillins. As illustrated in Scheme III, the alkaline hydrolysis of penicillins is first-order in both substrate and hydroxide ion and proceeds with cleavage of the /3-lactam ring to produce penicilloic acid. In the presence of an excess of cycloheptaamylose, the rate of disappearance of penicillin follows saturation kinetics as the cycloheptaamylose concentration is varied. By analogy to the hydrolysis of the phenyl acetates, this saturation behavior may be explained by inclusion of the penicillin side chain (the R group) within the cycloheptaamylose cavity prior to nucleophilic attack by a cycloheptaamylose alkoxide ion at the /3-lactam carbonyl. The presence of a covalent intermediate on the reaction pathway, although not isolated, was implicated by the observation that the rate of disappearance of penicillin is always greater than the rate of appearance of free penicilloic acid. 

More recently, Kaiser and coworkers reported enantiomeric specificity in the reaction of cyclohexaamylose with 3-carboxy-2,2,5,5-tetramethyl-pyrrolidin-l-oxy m-nitrophenyl ester (1), a spin label useful for identifying enzyme-substrate interactions (Flohr et al., 1971). In this case, the catalytic mechanism is identical to the scheme derived for the reactions of the cycloamyloses with phenyl acetates. In fact, the covalent intermediate, an acyl-cyclohexaamylose, was isolated. Maximal rate constants for appearance of m-nitrophenol at pH 8.62 (fc2), rate constants for hydrolysis of the covalent intermediate (fc3), and substrate binding constants (Kd) for the two enantiomers are presented in Table VIII. Significantly, specificity appears in the rates of acylation (fc2) rather than in either the strength of binding or the rate of deacylation. 

Photolysis of 4- and 3-nitrophenyl acetates (176 —> 177 178 —> 179) in neutral aqueous solution leads to the corresponding phenols with quantum yields 0.002 and O.OO6105 (equation 84). A greater difference in the photoreactivity (quantum yields of 0.002 and 0.129, respectively) is shown between 2-mcthoxy-4-nitrophenyl acetate 180 and 2-methoxy-5-nitrophenyl acetate 182. The nitro substituent clearly exhibits a meta-activating effect in the hydrolysis of phenyl acetates. 

For example, the hydrolysis of phenyl acetate (7.15) by carboxylesterase isozymes was investigated over a broad pH range, allowing many insights into their catalytic mechanisms [30] (see Chapt. 3). This substrate was also used together with various inhibitors to characterize esterases in human and rat tissues [31], Thus, the approximate values of Km (in pM) and Vmax (in pmol min 1 (g tissue)-1) in human tissues were 300 and 60 in liver micro-somes, 200 and 40 in liver cytosol, and 1500 and 250 in plasma, respective-... 

Reactions of a wide range of substituted phenyl acetates with six a-effect nucleophiles have revealed little or no difference, compared with phenolate nucleophiles, in the values of the Leffler parameters. As a result, the case for a special electronic explanation of the a-effect is considered unproven. Studies of the kinetics and mechanism of the aminolysis and alkaline hydrolysis of a series of 4-substituted (21) and 6-substituted naphthyl acetates (22) have revealed that, for electron-withdrawing substituents, aminolysis for both series proceeds through an unassisted nucleophilic substitution pathway. 

Hydrolysis of substituted phenyl acetates is catalysed by the Zn(II) complex of 1,5,9-triazacyclododecane (220). The results support the mechanism in which the ester is first complexed to the metal centre, and then water or hydroxide ion makes a nucleophilic attack at the complexed ester. ° ... 

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