4-Nitrophenyl acetate amines with

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... 

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. 

In nucleophilic catalysis the catalytic properties are a result of the intermediate formation of a 1-acylimidazole (Scheme 27). When the ester has a good leaving group, e.g. p-nitrophenyl acetate, the effective catalyst is the imidazole neutral molecule which increases in effectiveness as the basic pKa of the heterocycle increases. Where, however, the ester has a poor leaving group, e.g. p-cresol acetate, the imidazole anion becomes involved and general base catalysis predominates. Thus, for imidazoles with pjK"a 4 catalysis by the anion is the main reaction. Imidazole is a much more effective nucleophile than other amines in this type of reaction since it is a tertiary amine with little steric hindrance, and it is able to delocalize the positive charge which results from the nucleophilic addition to... 

The thiolates, though less sensitive to basicity, are more reactive than oxygen anions over the total accessible range of basicity, but intersect the amine line at ca. pA 12. Other reactive nucleophiles which do not fall in the amine, thiolate, or oxygen anion categories are fluoride, thiosulfate, nitrite, azide, and sulfite. Halides other than fluoride, and also thiocyanate, nitrate, sulfate, and thiourea have no reactivity towards p-nitrophenyl acetate (Jencks and Carriuolo, 1960a). The total lack of reactivity of thiocyanate, iodide, bromide, and thiourea, all very polarizable nucleophiles which are reactive to sp carbon, rules out any possibility that polarizability is at all important in nucleophilic reactions at the carbonyl carbon. In general, the order of nucleophilic reactivity to p-nitrophenyl acetate correlates well with nucleophilic reactivity to other carboxylic acid derivatives (see later). Nitrite, however, shows... 

To date, four main types of catalytic activity have been reported in detail for thermal polyamino acids. These are (with the most studied substrates in parentheses) hydrolyses (p-nitrophenyl acetate, p-nitro-phenyl phosphate, ATP), decarboxylations (OAA, glucuronic acid, pyruvic acid), and aminations (a-ketoglutaric acid, OAA, pyruvic acid, phenylpyruvic acid). The fourth type is a deamination reaction yielding a-ketoglutaric acid (51). For some of the actions of the thermal polymers the products are identified quantitatively, and the kinds of amino acid side chain necessary for activity in the polymer elucidated. In others, products have yet to be fully identified. The activities of thermal polyamino acids are manifest on substrates which range from chemically labile to relatively stable. 

Allyldiethylamine behaves similarly, but the yields are low since neither the starting amine nor the products are stable to the reaction conditions. For the efficiency of the cyclopropanation of the allylic systems under discussion, a comparison can be made between the triplet-sensitized photochemical reaction and the process carried out in the presence of copper or rhodium catalysts whereas with allyl halides and allyl ethers, the transition metal catalyzed reaction often produces higher yields (especially if tetraacetatodirhodium is used), the photochemical variant is the method of choice for allyl sulfides. The catalysts react with allyl sulfides (and with allyl selenides and allylamines, for that matter) exclusively via the ylide pathway (see Section 1.2.1.2.4.2.6.3.3. and Houben-Weyl, Vol. E19b, pll30). It should also be noted that the purely thermal decomposition of dimethyl diazomalonate in allyl sulfides produces no cyclopropane, but only the ylide-derived product in high yield.Very few cyclopropanes have been synthesized by photolysis of other diazocarbonyl compounds than a-diazo esters and a-diazo ketones, although this should not be impossible in several cases (e.g. a-diazo aldehydes, a-diazocarboxamides). Irradiation of a-diazo-a-(4-nitrophenyl)acetic acid in a mixture of 2-methylbut-2-ene and methanol gave mainly l-(4-nitrophenyl)-2,2,3-trimethylcyclo-propane-1-carboxylic acid (19, 71%) in addition to some O-H insertion product (10%). ... 

A zinc(II) hydroxo complex supported by a secondary amine-appended phenanthroline ligand (L2, Fig. 18b) has been reported to catalyze the hydrolysis of 4-nitrophenyl acetate with a second-order rate constant of 0.934 M-1 s-1.107 A mechanism involving attack of a terminal zinc hydroxide moiety on the 4-nitrophenyl acetate substrate has been proposed. 

Kinetic studies of the reaction of a series of secondary alicyclic amines with 4-nitrophenyl (A), 2,4-dinitrophenyl (B), and 2,4,6-trinitrophenyl acetate (C) in Et0H/H20 mixtures of varying composition showed that (i) the tetrahedral intermediate in the reaction of (A) was stabilized in 90 vol% EtOH (ii) for the reaction of (B), the mechanism is stepwise in water but concerted in the mixtures (iii) for the reaction of (C), the mechanism is concerted over the whole range of composition. ... 

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 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. 

Selection of Carboxylic Acid Derivatives. The competitive reaction between benzoic acid and 4-nitrophenyl acetate with amines, such as benzhydrazide and aniline, was carried out at room temperature for 10 min in the presence of condensing agent 1 (eq 2). 

When p-nitro-N,N-dimethylaniline (IVc) was ozonized at 0°C in ethyl acetate, methylene chloride, or methanol, a mixture of products resulted. In addition to the expected side-chain oxidation products— p-nitro-N-methylaniline (Vc), p-nitro-N-methyl formanilide (Vic)—a peroxide compound was formed. This peroxide, which is not formed until the solvents are removed, was shown by a series of experiments (described below) to be identical with di-[(N-methyl-p-nitrophenyl)-aminomethyl] peroxide (VII). Deoxygenation of VII with triethyl phosphite (7) yielded the ether VIII, which in turn decomposed at its melting point to the amine IX. 

The move towards catalytic reactions was initiated in 1983 by Hopkins and William. Phthalimide attached to a methacrylate residue acted as template. Hydrolysis after microgel formation with methyl methacrylate, 2-ethoxyethyl-methacrylate and ethylene glycol dimethacrylate left behind cavities possessing primary amine groups. Sha selectivity was confirmed by determination of hydrolysis rates between different 4-nitrophenyl esters. An acetate was hydrolysed considerably faster than a caproate [147]. Four years later Leonhardt and... 

The results of this reaction sequence are summarized in Scheme 3. Reaction of phenyl isocyanates with methylaminoacetaldehyde dimethyl acetal gave the corresponding ureas (5) in 90-95% yields. The urea was then treated with sodium hydride, and after the reaction mixture had cooled to 5°C, the aminating reagent was added all at once. Of three aminating reagents-O-(mesitylenesulfonyl) hydroxylamine (2), 0-(2,4-dinitrophenyl)hydroxylamine (3.) and 0-(4-nitrophenyl)hydroxylamine (2), the latter was preferred as it is a stable, recrystallizable solid. The crude product from this reaction mixture consisted of the semicarbazide and the urea which are conveniently separated by flash chromatography (silica gel). 

A side-chain methylenamino group reacts with a nitroso group (introduced in situ) when the compound is heated with mineral acid [2466]. An unusual reaction occurred when the nitro-t-amine (103.4) was refluxed with acetic anhydride and zinc chloride the course of this reaction may involve an A -oxide [2039]. When an o-nitroalkylamine is heated with ethoxide, the two functions are converted into a 1-hydroxyimidazole ring [3004]. Nitrosation of the pyrim-idinone (103.5) involves several steps including a Fischer-Hepp rearrangement of an iV-nitroso to a ring-C-nitroso the final product is a 6-(4 -nitrophenyl-amino)purin-2-one [2667]. In a weakly basic medium, the nitroamine (103.6) is cyclized to either the benzimidazole (when R == H), or the benzimidazolone (when R H). 

---