Phenyl acetate, alkaline 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... 

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... 

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. 

An early, qualitative observation of the exceptional reactivity of phenyl and naphthyl acetates having proximate formyl groups was made in 1946 (Vavon and Scandel, 1946). A quantitative study of the alkaline hydrolysis of the 2-, 3- and 4-formylphenyl acetates was made by Holleck et al. (1958). The 2-formyl ester [39] was very rapidly hydrolysed compared with the 3- and... 

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. 

Complexation with caffeine and theophylline-7-acetate depresses the rate of alkaline hydrolysis of substituted phenyl benzoates and is consistent with the formation of molecular complexes with 1 1 stoichiometry between the hosts and esters stacking of the xanthines is excluded as an explanation in the range of concentrations studied. Inhibition of hydrolysis is attributed to repulsion of the hydroxide ion from the host-ester complex by the extra hydrophobicity engendered by the xanthine host, as well as by the weaker binding of the transition state to the host compared with that in the host-ester complex. ... 

Hydroxyethyl)carbazole can be oxidized with copper(II) oxide-potassium hydroxide at 240°C to the carbazol-9-ylacetic acid the benzoate ester of the alcohol was cleaved to regenerate alcohol using phenyl Grignard reagent. The 9-acetic acid is also produced by alkaline hydrolysis of the corresponding nitrile. ... 

In Eq. 14, the reference of is shifted to that of H. The proximity effects of ortho substituents are well separated by Es and F terms according to Eq. 5. The coefficient values of Es and F terms, 0.17 and 0.77, are close enough to those for the alkaline hydrolysis of -substituted phenyl acetates 15). Thus, in support of the above discussion, the proximity effects of o-substituents are considered to be those on formation of the tetrahedral intermediate. 

Theoretical studies on 12 4-substituted phenyl acetates concluded that, in contrast to the proposed interpretation based on 13C NMR chemical shifts and ground-state destabilization calculations, the electrophilicity of the C=0 group increases due to the effect promoted by the electron-withdrawing groups in these systems.11 A DFT investigation of the alkaline hydrolysis of 4-nitrophenyl acetate has shown that a model including seven water molecules proceeds via a concerted transition state.12... 

That a single solvent molecule clustered to a nucleophile can drastically change the reaction pathway has been demonstrated by studying the reaction of phenyl acetate with methoxide ion in the gas phase [671, 672]. Alkaline hydrolysis of esters in solution is known to proceed by attack of the nucleophile at the carbonyl carbon atom to form a tetrahedral intermediate, followed by cleavage of the acyl-oxygen bond (Bac2 mechanism) cf. Eq. (5-138a). 

Another important research direction is the mimieking of enzymes and the construction of selective catalysts. For these purposes, the polymer is imprinted with the desired reaetion-product or better, a molecule which resembles the transition state of the reaction adducts. If the educts bind specifically to the recognition site, they become confined into these micro-reactors and are supposed to react faster and more defined than outside the cavities [445]. Examples for reactions in the presence of such synthetic enzymes can be found in [452,453,454,455,456,457] (cf Figure 40c). First positive results have been reported, e.g. an synthetic esterase , increasing the rate of alkaline hydrolysis of substituted phenyl-(2-(4-carboxy-phenyl)-acetic esters for 80 times [488] and Diels-Alder catalysis fiuic-tional holes containing titanium lewis-acids [489]... 

For the preparation of the 2-amino-4(3i7)-oxo analogues of this series, the 2,4-diamino-9,10-dehydro derivative (IV.175) was converted to (IV.187) (88%, yield) by heating in 1 M NaOH under reflux for 3 h [140a]. Treatment of (IV.187) with acetic anhydride containing a catalytic amount of 4- NJ -dimethylamino)pyridine afforded the 2-acetamido-4-oxo mixed anhydride (IV. 188) (84%), which on careful alkaline hydrolysis was converted to the protected acid (IV. 189) (77%,). Coupling to diethyl L-glutamate in V-methyl-pyrrolidin-2-one in the presence of phenyl iV-phenylphosphoramidochloridate... 

A simple mechanistic use of the a" correlation is the diagnosis that addition of hydroxide to the ester is the rate-limiting step in the alkaline hydrolysis of phenyl acetates. The rate constant koH correlates much better with a than with a ... 

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