4-Nitrophenyl acetate, reaction with

FIGURE 1. Br0nsted-type plot for reactions of p-nitrophenyl acetate (PNPA) with anionic oxygen nucleophiles. The a-nucleophiles are shown as solid circles. Data taken from Jencks and Gilchrist, J. Am. Chem. Soc., 90, 2622 and reprinted with permission. Copyright (1968) American Chemical Society... 

In 1952, Hartley and Kilby showed that p-nitrophenyl acetate reacts with chymotrypsin, and advanced a two-step mechanism for the process (Hartley and Kilby, 1952). Two years later Hartley showed that a burst of p-nitrophenol was produced in the reaction (Hartley and Kilby, 1954). That is to say, a graph of the production of p-nitrophenol from the chymotryptic hydrolysis of p-nitrophenyl acetate does not seem to begin at the origin, but instead a small amount of p-nitrophenol is produced very rapidly. Fur-... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Certain molecules that can permit concerted proton transfers are efficient catalysts for reactions at carbonyl centers. An example is the catalytic effect that 2-pyridone has on the aminolysis of esters. Although neither a strong base (pA aH+ = 0.75) nor a strong acid (pJsfa = 11.6), 2-pyridone is an effective catalyst of the reaction of -butylamine with 4-nitrophenyl acetate. The overall rate is more than 500 times greater when 2-pyridone acts... 

Sodium acetate reacts with /p-nitrophenyl benzoates to give mixed anhydrides if the reaction is conducted in a polar aprotic solvent in the presence of a crown ether. The reaction is strongly accelerated by quartemary nitrogen groups substituted at the orthc position. Explain the basis for the enhanced reactivity of these compounds. 

When Jencks reacted hydroxylamine with p-nitrophenyl acetate, p-nitrophenolate ion was released at a rate faster than that at which acetohydroxamic acid was formed. This burst effect is evidence for a two-step reaction. In this case the intermediate is O-acetylhydroxylamine, which subsequently reacts with hydroxylamine to form the hydroxamic acid. 

These Br nsted-type plots often seem to be scatter diagrams until the points are collated into groups related by specific structural features. Thus, p-nitrophenyl acetate gives four separate, but parallel, lines for reactions with pyridines, anilines, imidazoles, and oxygen nucleophiles.Figure 7-4 shows such a plot for the reaction of trans-cmmm c anhydride with primary and secondary aliphatic amines to give substituted cinnamamides.All of the primary amines without substituents on the a carbon (R-CHi-NHi) fall on a line of slope 0.62 cyclopentylamine also lies on this line. If this line is characteristic of normal behavior, most of the deviations become qualitatively explicable. The line drawn through the secondary amines (slope 1.98) connects amines with the structure R-CHi-NH-CHi-R. The different steric requirements in the acylation reaction and in the model process... 

The curvature may be an artifact of a selection of nucleophiles of mixed structural types chosen to display a wide range in pAo. Buncel et al. ° varied pK by changing the solvent composition over a limited range rather than by changing the structure. They studied the reaction between X-C6H4-CT and p-nitrophenyl acetate in 40-90 mol% dimethylsulfoxide—water mixtures with just three X substituents... 

The most reliable method of preparing benzofuroxans is by decomposition of o-nitrophenyl azides. Decomposition can be achieved by irradiation, or more usually by pyrolysis temperatures between 100° and 1.50° are commonly used. Refluxing in glacial acetic acid is the recommended procedure for 4- or 5-sub-stituted 2-nitrophenyl azides, but with 3- or 6-substituted compounds higher boiling solvents are usually necessary. Quantitative studies on the reaction rate have been made, and a cyclic transition state invoked, an argument which has been used to account for the greater difficulty of decomposition of the 6-substituted 2-nitrophenyl azides. Substituent effects on the reaction rate have also been correlated with Hammett a constants, ... 

The positive bromination of aromatics ethers was first studied by Bradfield et al.193 and by Branch and Jones194. The reaction of hypobromous acid in 75 % aqueous acetic acid with benzyl 4-nitrophenyl ether and 4-nitrophenetole at 20 °C was very rapid and approximately second-order193. The value of k2/[H+] remained constant in the [H+] range 0.005-0.090 M for the effect of added mineral acids on the bromination of 4-nitroanisole and 4-nitrophenetole (at 19.8 °C)194. The variation in reaction rate with the percentage of acetic acid in the medium was also studied and showed a large increase in the 0-10 % range with a levelling off at approximately 25 % acetic acid (Table 52) this was attributed... 

Reaction of p-nitrophenyl 2-(p-tolylsulfinyl)acetate 161 with aryl aldimines in the presence of imidazole was found to give /j-lactams 162 and amides 163206. In the cyclization, only the two 3,4-trans derivatives were formed out of a possible four diastereomeric pairs and, interestingly, the ratio of two diastereomeric pairs went up to 6.7 1. This means not only that internal asymmetric induction207 affords the trans derivative, but that also a relatively high asymmetric induction took place during the reaction. 

The hydrolysis of p-nitrophenyl acetate and bis(p-nitrophenyl phosphate) are frequently used to probe hydrolytic activity. A problem with some other dinuclear systems is that the Zn units are held together by bridging ligands which can be cleaved on reaction with the substrate.440 This is not the case in a ditopic ligand such as those designed by Lippard and co-workers based on Kemp s triacid imide with a xylyl spacer.441,442 Both zinc dimers and mixed metal dimers were formed and a structure characterized with a bridging phosphodiester (Figure 6). 

Values of /c2 and Kd for the reactions of the cycloamyloses with a variety of phenyl acetates are presented in Table IV. The rate constants are normalized in the fourth column of this table to show the maximum accelerations imposed by the cycloamyloses. These accelerations vary from 10% for p-f-butylphenyl acetate to 260-fold for m-f-butylphenyl acetate, again showing the clear specificity of the cycloamyloses for meta-substituted esters. Moreover, these data reveal that the rate accelerations and consequent specificity are unrelated to the strength of binding. For example, although p-nitrophenyl acetate forms a more stable complex with cyclohexa-amylose than does m-nitrophenyl acetate, the maximal rate acceleration, h/kan, is much greater for the meta isomer. 

At the start of this section the cleavage of meta- and para-substituted phenyl acetates by a- and )S-CD was discussed in detail and a variety of evidence was cited that is consistent with the mechanisms A and B, in Scheme 2. Further support for the view that para-substituents tend to force the phenyl group out of the cavity (Scheme 2B) comes from the different effects that neutral additives (potential inhibitors) have on the cleavage of m- and p-nitrophenyl acetate (mNPA and pNPA). In brief, species which bind to CDs, and inhibit the reaction of mNPA, do not necessarily inhibit that of pNPA (Tee and Hoeven, 1989 Tee et al., 1993b). 

Second-order rate constants for the reaction of imidazole derivatives with p-nitrophenyl acetate... 

Activated esters of A-alkoxycarbonylamino acids are prepared by two approaches, activation of the acid followed by reaction with the hydroxy compound, and trans-esterification. Most of the products are stable enough to be purified by washing a solution of the ester in an organic solvent with aqueous solutions. A few that are not crystalline are purified by passage through a column of silica. The commonly used method for their preparation is addition of dicyclohexylcarbodiimide to a cold mixture of the reactants in dimethylformamide or ethyl acetate. The first Boc-amino acid nitrophenyl esters were obtained using pyridine as solvent. Pyridine generates the nitrophenoxide ion that is more reactive. For one type of ester, 2-hydroxypyridino... 

The photodecarboxylation of nitrophenyl acetate in aqueous media was also investigated recently89 -92, especially with respect to the kinetic and spectral properties of the photogenerated p-nitrobenzyl carbanion its triplet state (Xmax ca 290 nm) was identified to have a lifetime of 90 nanoseconds at pH > 5.0. The proposed reaction mechanism following 266-nm laser excitation of p-nitrophenyl acetate is summarized in Scheme 792. 

Kirsh et al. 42) prepared apolar derivatives of poly(4-vinylpyridine) by benzylation. With nitrophenyl acetate as the substrate the benzylated catalyst is 100 times more effective than 4-ethylpyridine. A double-displacement mechanism was observed. The rate constants for deacylation of the acylpoly(vinylpyridine) derivatives were about 4 x 10" /sec. The comparable value for a-chymotrypsin is 8 x 10 /sec. The factor of 20 seems small, but it should be kept in mind that deacetylation of a-chymotrypsin is very slow compared with the deacylation reactions involving the natural substrates of the enzyme. 

The final intriguing use of CLAs is in the immobilization of enzymes in the soapy shell in order to carry out an enzymatic reaction. Thus the hydrolysis of -nitrophenyl acetate to / -nitrophenol has been demonstrated by immobilizing a lipase into the shell of a CLA. The CLAs were then pumped through a cross-fiow membrane, where they were separated and recycled, with the product appearing in the permeate [70]. 

Bruice and Sturtevant, (1959) and Bruice, (1959) found extremely facile intramolecular nucleophilic attack by neighbouring imidazole in the hydrolysis of p-nitrophenyl 7-(4-imidazoyl)butyrate [19]. The rate constant for imidazole participation (release of p-nitro-phenolate) in this reaction is nearly identical with the rate constant for a-chymotrypsin catalysed release of p-nitrophenolate ion [190 min in equation (11) at pH 7 and 25°] from p-nitrophenyl acetate. Comparison of the rate constant for intramolecular imidazole participation to that for the analogous bimolecular reaction (imidazole attack on p-nitrophenyl acetate) (s" /m s )... 

Bruice and Lapinski (1958) reported that logarithms of second-order rate constants for reaction of p-substituted phenoxide ions with p-nitrophenyl acetate were a linear function of the p/sfa-value of the phenol with a slope of 0-8. Phenolate ions cannot displace... 

Reaction of the m-nitrophenyl ester of pyridine-2,5-dicarboxylic acid with cyclodextrin (see Section 3) gives a picolinate ester [52] of a cyclodextrin secondary hydroxyl group (Breslow, 1971 Breslow and Overman, 1970) which will bind metal ions or a metal ion-pyridine carboxaldoxime complex. Such a complex will catalyse hydrolysis of p-nitrophenyl acetate bound within the cyclodextrin cavity leading to a rate constant approximately 2000-fold greater at... 

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