4- Nitrophenyl acetate, aminolysis

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... 

A catalytic effect that may be of the same type as the mimicry of acyl transferase enzymes is reported by Gandour et al. (1978). They describe the rate enhancement of the aminolysis of p-nitrophenyl acetate in the presence of bis(2,6-pyridinyl) crown ethers [328] and [329] in chlorobenzene. The rate of... 

The catalysis by a protected nucleoside of the aminolysis by butylamine of / -nitrophenyl acetate in benzene (Scheme 3) has been reported. Interestingly, only 2, y, 5 -<9-tris(t-butyldimethylsilyl)cytidine showed any marked catalytic effect, the adenosine, guanosine and uridine analogues behaving merely as weak general base... 

If an amine P-NH2 is used in the aqueous solution, one obtains RCONHP instead of RCOOH. Rates of cleavage of three acyl nitrophenyl esters were followed by the appearance of p-nitrophenolate ion as reflected by increased absorbances at 400 nm. The reaction was carried out at pH 9.0, in 0.02 M tris(hydroxymethyl)aminomethane buffer, at 25°C. Rate constants were determined from measurements under pseudo-first-order conditions, with the residue molarity of primary amine present in approximately tenfold excess. First-order rate graphs were linear for at least 80% of the reaction. With nitrophenyl acetate and nitrophenyl caproate, the initial ester concentration was 6.66xlO 5M. With nitrophenyl laur-ate at this concentration, aminolysis by polymer was too fast to follow and, therefore, both substrate and amine were diluted tenfold for rate measurements. 

The influence of a series of alkyl-substituted 3-cyano-2-pyridones (24 R = Me, Et, Pti, Bu1) and (25 n = 1, 2, 3) on the kinetics of the aminolysis in CHCI3 of / -nitrophenyl acetate (27) by butylamine (26) was studied. It was proposed that the pyridone catalysts (present as 1 1 pyridone-amine complexes) form a weakly bound... 

Figure 3. Bransted-type plots for aminolysis in 1 M KC1 at 25 °C 0,2-nitrophenyl acetate , 3-chlorobenzoic acid 0,2,6-dinitrobenzoic acid.

Both the magnitude and the direction of the effects of cationic, anionic, and neutral micelles on the rate of aminolysis of p-nitrophenyl acetate... 

Menger, F.M. (1966) The aminolysis and amidinolysis of p-nitrophenyl acetate in chlorobenzene. A facile bifunctional reactivity. Journal of the American Chemical Society, 88, 3081-3084. 

The aminolysis of several substituted p-nitrophenyl acetates exhibits good second-order kinetics. Some of the observed rate constants are given below. Plot the data according to the Hammett equation. What is the value of p Are the... 

The aminolysis of 4-nitrophenyl acetate in chlorobenzene occurs with the intermediate formation of a tetrahedral adduct [equation (2)] causing the generation of an ammonium ion. The latter may be stabilized by hydrogen bonding to a crown or poly ether. A flexible polyether is a better catalyst for this reaction than relatively rigid crowns. ... 

Carboxylates act as general base catalysts for the aminolysis of 4-nitrophenyl acetate in chlorobenzene and the rate of reaction is enhanced in the presence of crown-ether-complexed potassium carboxylates. ... 

The aminolysis of 4-nitrophenyl acetate in reversed micelles of dodecyl-ammonium propionate (DAP) is dependent upon the chain length of the amine and shows a rate increase of up to 50-fold compared with that in the absence of surfactant, which is attributed to catalysis by the surfactant The addition of water decreases the observed rates owing to hydration of the dodecylammonium propionate head groups. In the presence of bis(2-ethylhexyl) sodium sulpho-succinate the rate of hydrolysis of 4-nitrophenyl carboxylates catalysed by A -methylimidazole decreases with increasing chain length of the ester group and increases as a function of added water reflecting the importance of distribution of the reactants between the bulk solvent and the micellar water pool . ... 

The kinetics of the aminolysis of 4-nitrophenyl acetate by piperidine were studied in nine ILs and compared to data in nine organic solvents. The rates in the ILs were about equivalent to those in MeCN and THF, and for [Bmim]BF4, the rate was only sevenfold less than that in DMSO (dimethyl sulfoxide). A Br0nsted-type plot for the aminolysis of [Bmim]BF4 by four secondary amines (piperidine, morpholine, formylpiperazine, and l-(2-hydroxyethyl)piperazine), which could only be generated after determination of their pKa values (which was accomplished by cyclic voltammetry at a P-Pt electrode), was linear (P = 0.77) and revealed that the mechanism was stepwise, different from the concerted mechanism found in conventional solvents. ... 

A good esterase mimic, exhibiting burst kinetics and turnover, has been constructed by attaching to 3-amino-/3-cyclodextrin a bound zinc cation and an oxime anion. This construct (186) was observed to catalyse the hydrolysis of p-nitrophenyl acetate (PNPA) extremely effectively (A cat/ unoat = 22 600 for the initial fast deacylation step). As in the hydrolysis of PNPA by chymotrypsin, this fast step was followed by a slower reaction in which the acyl- enzyme intermediate suffered hydrolysis.The attachment to the a-face of yS-cyclodextrin of a series of )-aminoalkyl groups has produced a lengthening arm that has permitted a study of the catalysed aminolysis of jo-nitrophenyl acetate (PNPA). The construct containing the three-carbon linker (187 n = 3) was found to be the most effective accelerant, but only two-fold better than that containing the six-carbon linker (187 n = 6). The proposed mechanism involves the fast reversible formation of a complex between the modified CD and PNPA, which, in a slow step, yields the amide (188) (Scheme 34). 

The reaction of p-nitrophenyl acetate with 1,3-diaminopropane in chlorobenzene is intramolecularly catalysed [72]. The reaction of n-butylamine with p-nitrophenyl acetate in chlorobenzene is second order (kj) in amine and no reaction which is first order in amine was detected. In contrast, the reaction with 1,3-diaminopropane has both terms of first and of second-order in amine, and the rate constant for the reaction which is first-order in amine is at least 300 times greater than that for the undetected reaction of n-butylamine, while the rate constant for the reaction which is second-order in amine is about 14 times greater than the analogous reaction of n-butylamine [72]. Since breakdown of the tetrahedral intermediate is rate-limiting in the aminolysis of aryl esters in aprotic solvents [32], the intramolecular catalysis presumably functions in this step, possibly as symbolized by 46. 

The potential of the polar cavity of macrocyclic ionophores such as (78) to stabilize polar transition states by electrostatic interaction has been suggested as an explanation for the catalytic effect of (78) on the aminolysis of p- nitrophenyl acetate by butylamine. 

Theoretical studies of the catalysis by 2-pyridone (17) and its tautomer, 2-hydroxypyri-dine, of the aminolysis of p-nitrophenyl acetate (16) by BUNH2 in the gas phase and in... 

Aminolysis of phenyl dithioacetates,8 pyridinolysis of O-ethyl dithiocarbonates,9 reaction of pyrrolidine with O-ethyl 5-aryl dithiocarbonates,10 aminolysis of chlorothionformates,11 pyridinolysis of alkyl aryl thioncarbonates,12 reaction of anionic nucleophiles with nitrophenyl benzoate and its sulfur analogues,36 hydrolysis of methyl benzoate and phenyl acetate containing SMe, SOMe and S02Me substituents,42 solvolysis of phenyl chlorothioformate,79 synthesis of new thiadiazoles,124 examination of a neighbouring sulfonium group in ester hydrolysis,136 hydrolysis of V-type nerve agents,250 and the reactions of peroxymonosulfate ion with phosphorus(V) esters have all been looked at previously in this review. 

Kinetic studies of the aminolysis of p-nitrophenyl decanoate and acetate by BuNH2 in chlorobenzene in the presence of a glyme with four oxygen atoms, Me0(CH2CH20)3 Me, have revealed a new pathway that shows a first-order dependence on the concentration of the phase transfer catalyst and a second-order dependence on BuNH2.71... 

Even at reactant concentrations well below critical micelle concentrations, hydro-phobic interactions may result in marked rate accelerations. Thus, the rates of bimo-lecular aminolysis of 4-nitrophenyl decanoate and acetate by n-decylamine and ethyl-amine have been determined in aqueous solution and a distinct rate enhancement in the aminolysis of the long chain ester by the long chain amine was reported [405, 406]. As shown in Table 5-24, the ratio /j ecyiamme ethyiamme 4-nitrophenyl decanoate is 317 h That is, -decylamine attacks the long-chain ester 47 times faster than expected on the... 

Thus, two types of active esters are of interest those formed from an acid and a substituted phenol (12-15) and those formed from an acid and a substituted hydroxylamine (16-19). Both types are reactive by virtue of the electron-withdrawing properties of the OR moiety in 2. The level of activation of the substituted phenyl esters varies directly with the electronic effect going from 4-nitrophenyl to 2,4,5-trichlorophenyl, pentachlorophenyl, and pentafluorophenyl, which corresponds with the increasing acidity of the phenols. A diminution in the rate of aminolysis is caused by the presence of a substituent in the ortho position of the ring.f l An additional phenomenon contributes to the reactivity of the esters formed from substituted hydroxylamines, namely anchimeric assistance. Since the anoinolysis of active esters is a bimolecular reaction, it is dependent on concentration and can be forced to completion by an excess of one of the reactants. Aminolysis is also characterized by a pronounced dependence on the polarity of the solvent in particular for the esters formed from substituted phenols, the half-life of a 2,4,5-trichlorophenyl ester in the presence of benzylamine being one hundred times less in dimethylformamide than in benzene. Furthermore, aminolysis is catalyzed by mild acid such as acetic acid. The rate of anoinolysis is slowed if the side chain of the active ester contains a P-methyl substituent. 

Bodanszky et al. 1969) is accompanied by diminished sensitivity to steric hindrance and also by decreased dependence of the reaction rates from the nature of the solvent used in the coupling step. Para-nitrophenyl esters are most active in highly polar media, such as dimethylformamide or dimethylsulfoxide, less active in ethyl acetate, dioxane or tetrahydrofurane and rather inert in methylene chloride or chloroform. In spite of these advantages mainly the para derivatives are used, probably because a major improvement in peptide synthesis rendered these differences less important, to wit, the discovery of the catalytic effect of 1-hydroxybenzotriazole (Konig and Geiger 1973) on aminolysis of active esters. This effect could be rationalized by the assumption of a ternary complex between active ester, amine and catalyst... 

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