P-Nitrophenyl formate

A-Formyl-Wang-O-hydroxylamine 222 resin was prepared by treating Wang-O-hydroxylamine resin 221 with p-nitrophenyl formate and 10% pyridine in DMF at room temperature for 16 h (Scheme 95). 

Formoxy. . ., p-Nitrophenyl formate, Thioformic acid esters... 

An aq. soln. of L-ornithine monohydrochloride neutralized with an equivalent amount of aq. 1 N NaOH-soln., then p-nitrophenyl formate in tetrahydrofuran added dropwise with ice-cooling and stirring, which is continued 6 hrs. at room temp. N -formyl-L-ornithine. Y 52%. F. e. s. K. Okawa and S. Hase, Bull. Chem. Soc. Japan 36, 754 (1963). 

Conversion of p-nitrophenol into p-nitrophenyl formate in good yield by reaction with this in situ generated reagent confirmed that it can act as a formylating agent. However, attempts to formylate aromatics failed due to the instability of the anhydride above -40 C. Also, the presence of acid catalysts leads to the decomposition of the formic anhydride even at low temperatures. 

Another method for formylation of amines is with p-nitrophenyl formate, which usually gives products in high yield. However, removing the last traces of the p-nitrophenol is diffieult. ... 

Alkyl p-Nitrophenyl Carbonate ROCOOC6H4-/7-NO2 (Chart 2) Formation/Cleavage ... 

If, however, the /7-nitrophenyl ester of iV-henzoyl-L-leucine is treated with 1-methyl-piperidine in chloroform for 30 min and then coupled with glycine ethyl ester, the dipeptide isolated is almost completely racemic. Furthermore, treatment of the p-nitrophenyl ester of iV-benzoyl-L-leucine with 1-methylpiperidine alone leads to the formation of a crystalline material, C13H15NO2, having strong IR bands at 1832 and 1664 cm . Explain these observations, and suggest a reasonable stmcture for the crystalline product. 

In the second major method of peptide synthesis the carboxyl group is activated by converting it to an active ester, usually a p-nitrophenyl ester. Recall from Section 20.12 that esters react with ammonia and amines to give fflnides. p-Nitrophenyl esters are much more reactive than methyl and ethyl esters in these reactions because p-nitrophenoxide is a better (less basic) leaving group than methoxide and ethoxide. Simply allowing the active ester and a C-protected amino acid to stand in a suitable solvent is sufficient to bring about peptide bond formation by nucleophilic acyl substitution. 

We have disclosed that the ligands 4c, 10, and 77, when complexed with a metal ion such as Zn2 +, Ni2+, or Co2+, become highly active toward the hydrolysis of p-nitrophenyl picolinate (7). The catalysis is most likely to occur through formation of a ternary complex in the transition state or in reactive intermediates. The metal ion in such a complex serves to activate the ligand hydroxyl group for nucleophilic attack and to orient the substrate into a favorable position to undergo the reaction. 

Olah and coworkers56 found that treatment of dialkyl, arylalkyl and diaryl sulphides with nitronium hexafluorophosphate (or tetrafluoroborate) 32 at —78° in methylene chloride resulted in the formation of sulphoxides in moderate to high yields (Table 3). In the oxidation of diphenyl sulphide which affords diphenyl sulphoxide in 95% yield, small amounts of the ring nitration products (o- and p-nitrophenyl phenyl sulphides) were formed. However, diphenyl sulphone and nitrophenyl phenyl sulphoxide were not detected among the reaction products. 

In the course of this study, the authors determined /Lvalues for dibenzyl, methyl phenyl, methyl p-nitrophenyl, di-p-tolyl, di-isopropyl and tetramethylene sulphoxides and for diethyl, dipropyl and dibutyl sulphites. The /Lscales are applied to the various reactions or the spectral measurements. The /Lscales have been divided into either family-dependent (FD) types, which means two or more compounds can share the same /Lscale, family-independent (FI) types. Consequently, a variety of /Lscales are now available for various families of the bases, including 29 aldehydes and ketones, 17 carboxylic amides and ureas, 14 carboxylic acids esters, 4 acyl halides, 5 nitriles, 10 ethers, 16 phosphine oxides, 12 sulphinyl compounds, 15 pyridines and pyrimidines, 16 sp3 hybridized amines and 10 alcohols. The enthalpies of formation of the hydrogen bond of 4-fluorophenol with both sulphoxides and phosphine oxides and related derivatives fit the empirical equation 18, where the standard deviation is y = 0.983. Several averaged scales are shown in Table 1588. 

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

Sulfate monoesters can react by dissociative paths, and this is the favored path. Whether such reactions are concerted or involve a very short-lived sulfur trioxide intermediate has been the subject of debate. ° Benkovic and Benkovic reported evidence suggesting that the nucleophile is present (though there is little bond formation) in the transition state for the reaction of amines with p-nitrophenyl sulfate. Alkyl esters of sulfuric or sulfonic acids normally react with C-0 cleavage only when this is disfavored, as in aryl esters, does one see S-0 cleavage. Sulfate diester... 

An estimate of the rate enhancement associated with the intramolecular phosphorylation can be made by using isopropyl p-nitrophenyl methyl-phosphonate as a model for the covalent intermediate formed in the initial step of the reaction of cycloheptaamylose with bis (p-nitrophenyl) me thy 1-phosphonate. The first-order rate constant for the alkaline hydrolysis of isopropyl p-nitrophenyl methylphosphonate at pH 9.86 can be obtained from the data of van Hooidonk and Groos (1970) kun = 1.4 X 10-5 sec-1. This value may be compared with the maximal rate constant for the reaction of cycloheptaamylose with bis(p-nitrophenyl) methylphosphonate— k2 = 1.59 X 10-1 sec-1 at pH 9.86—which must be a minimal value for the rate of the intramolecular phosphorylation. This comparison implies a kinetic acceleration of at least 104 which is similar to rate enhancements associated with the formation of cyclic phosphates from nucleoside phosphate diesters. 

Figure 6.1 The Wedekind trifunctional crosslinker can react with amine groups via its p-nitrophenyl ester to form amide bond linkages. The phenyl azide group then can be photoactivated with UV light to generate covalent bond formation with a second molecule. The biotin side chain provides binding capability with avidin or streptavidin probes.

The rates of reaction of both enantiomers of amino-acid esters in the presence of (S)-[324] are the same, but with (S)-[323] they are in most cases different. The reactions of L-amino acid esters in the presence of (S)-[323] are faster than those in the presence of (R)-[323] by factors of 9.2 (R = i-Pr), 8.2 (R = C6H5CH2) and 6.0 (R = i-Bu). No difference in rates is observed for L-alanine p-nitrophenyl ester. The results were explained in terms of the formation of diastereomeric tetrahedral intermediates [325] and [326]. The bulk of the group R will determine how much the complex stability of the (D)-complex decreases relative to that of the (L)-complex, which difference is reflected in the activation energy of the rate-determining step. 

Micellar microenvironments may be used for differentiating courses of reaction. Thus, cationic micelles efficiently suppressed the SN1 reaction of 1-bromo-2-phenylpropane (Lapinte and Viout, 1973) and of 3-bromo-3-phenylpropionate (Bunton et al., 1974). Tagaki et al. (1976) found that the facilitated formation of carbanion intermediates changed the course of reaction of p-nitrophenyl esters. 

The behavior of metal ions in reversed micelles may be more interesting, since the reversed micelle provides less solvated metal ions in its core (Sunamoto and Hamada, 1978). Through kinetic studies on the hydrolysis of the p-nitrophenyl ester of norleucine in reversed micelles of Aerosol OT and CC14 which solubilize aqueous cupric nitrate, Sunamoto et al. (1978) observed the formation of naked copper(II) ion this easily formed a complex with the substrate ester (formation constant kc = 108—109). The complexed substrate was rapidly hydrolyzed by free water molecules acting as effective nucleophiles. 

The formation of /7-nitro-AW-dimethylaniline (in addition to the expected p-nitrophenyl ether) in the reaction of nitrophenate ion with the alkoxyphosphonium salts (158) indicates the intermediacy of the relatively stable interconverting phos-phoranes (159). Loss of dimethylamide ion gives the salt (160), which subsequently undergoes SurAr reactions.142... 

The triplet state of 4-nitrobiphenyl has been observed in laser flashed benzene solution (. max 540 nm, t 10 ns at room temperature) 32). 4-Nitrobiphenyl and 4,4 -dinitrobiphenyl have been photoreduced by sodium formate in buffered aqueous methanolic solution 43i>) 15% 4-aminobiphenyl and 11% 4,4 -azobi-phenyl as well as 49% 4-amino-4 -nitrobiphenyl and 20% 4,4 -(p-nitrophenyl)-azoxybenzene, respectively, could be isolated and identified by comparison with authentic samples. 

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