4-Nitrophenyl phenyl aminolysis

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. 

Aminolysis of a series of aryl 2,4-dinitrophenyl carbonates by a series of quinuclidines gave linear Br0nsted-type plots, the magnitudes of their slopes confirming their mechanisms as concerted.40 A comparison41 of the aminolysis, by primary amines, of 4-nitrophenyl phenyl carbonate (31 X = O) with its thiono analogue (31 X = S) is discussed in the section Thioacids, Thioesters, Thiolactones, and Thiocarbonates below. 

Kinetics of the aminolysis of phenyl and methyl 4-nitrophenyl thionocarbonates [Ph- and Me-0C(=S)0C6H4-4-N02] by secondary cyclic amines, to give the corresponding thionocarbamates, have been measured in aqueous solution at 25 °C. ... 

Kinetic studies of the reaction of Z-phenyl cyclopropanecarboxylates (1) with X-benzylamines (2) in acetonitrile at 55 °C have been carried out. The reaction proceeds by a stepwise mechanism in which the rate-determining step is the breakdown of the zwitterionic tetrahedral intermediate, T, with a hydrogen-bonded four-centre type transition state (3). The results of studies of the aminolysis reactions of ethyl Z-phenyl carbonates (4) with benzylamines (2) in acetonitrile at 25 °C were consistent with a four- (5) and a six-centred transition state (6) for the uncatalysed and catalysed path, respectively. The neutral hydrolysis of p-nitrophenyl trifluoroacetate in acetonitrile solvent has been studied by varying the molarities of water from 1.0 to 5.0 at 25 °C. The reaction was found to be third order in water. The kinetic solvent isotope effect was (A h2o/ D2o) = 2.90 0.12. Proton inventories at each molarity of water studied were consistent with an eight-membered cyclic transition state (7) model. 

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. 

Peptide bond formation between an active ester and an amino group is a simple nucleophilic displacement reaction that occurs spontaneously at room temperature through formation of tetrahedral intermediate 4 (Scheme 1) whose breakdown is the rate-limiting step. The rates of aminolysis of substituted phenyl esters vary directly with the electron-withdrawing strengths of the moieties, which correspond with the relative acidities of the parent phenols, in the order pentafluorophenyl 15 > pentachlorophenyl 14 > 2,4,5-trichlorophenyl 13 >4-nitrophenyl 4-Oxo-3,4-dihydrobenzotriazine-3-yl esters 18 are five times as reactive... 

The first reported solid-phase synthesis of head-to-tail cyclic peptides was based on the intramolecular aminolysis of resin-bound o-nitrophenyl esters. The cyclization proceeds concurrently to cleave the peptide from the resin, after deprotection and neutralization of the AT-terminal residue (Scheme 2A). Accordingly, Fridkin et al. [3] reported the preparation of several simple, unhindered cyclopeptides, such as cyc/o(Ala-Gly-Ala-Ala). Similarly, Flanigan and Marshall [4] obtained activation of the resin-bound peptide ester, after elongation of the peptide chain, by oxidation of the 4-(methyl-thio)phenyl (MTP) linker to a sulfonyl ester. Subsquent deblocking of the A-terminal residue and intramolecular condensation yielded the desired cyclic peptide. However, this method was found not to be suitable for the synthesis of longer and more hindered cyclic peptides [5]. 

An interesting example of intra-polymeric catalysis is provided by the effect of polymer side chains on the aminolysis of polymer-bound nitrophenyl ester [41a], as illustrated in Fig. 10. Thus, apparent reactivity of the polymer-bound carbonyl groups is substantially increased by changing the polymer side chains from phenyl to methoxycarbonyl, and to dimethylamide. This type of intra-polymeric catalysis (shown schematically by species 9 in Fig. 11) assumes special significance in crosslinked polymers and solid phase synthesis. An important implication of this catalytic effect for polymer synthesis is that when an activated polymer intermediate (8) is not sufficiently reactive towards a given nucleophile, polymer reactivity can be enhanced by partial aminolysis with dimethyl-amine [25]. 

Noting the fairly pronounced reactivity of phenyl esters in aminolysis Bodanszky concluded [21] that the enhanced aminolysis rates observed with thiophenyl esters [4] are due only in part to their thiol ester character and perhaps to a major extent to the fact that they are aryl esters. This conclusion was based on the fundamental studies of Gordon, Miller and Day [22] who found extremely high rates in the ammonolysis of phenyl and vinyl esters. To further increase the electronic effect operative in phenyl esters, their nitro-derivatives were prepared and examined. For practical application p-nitrophenyl esters were... 

Kinetic studies on the reactions of X-phenyl chloroformates (52) with Y-pyridines in MeCN showed that the electron-rich formate moiety (O—C=0) overlaps with the pyridine tt-system, allowing rate-limiting formation of a tetrahedral intermediate. A similar conclusion was made following kinetic studies of the reactions of secondary alicyclic amines with phenyl (52 X = H) and 4-nitrophenyl chloroformate (52 X = 4-NO2) in aqueous solution, but the results for the aminolysis (anilines) of the same substrates in MeCN were considered to be more consistent with a concerted process. ... 

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