2,4-Dinitrophenyl phosphate

As is apparent from Fig. 1, the dianions of monoalkyl phosphates normally resist hydrolysis. However, for leaving groups whose conjugate acids exhibit a pKa < 5 in water, hydrolysis of the dianion becomes faster than that of the monoanion. Fig. 2 shows a pH profile characteristic of this situation. Whereas the hydrolysis rate of 2,4,6-trichlorophenyl phosphate (pKa of the phenol 6.1) still shows the typical monoanion preference as seen for methyl phosphates (Fig. 1), the dianion of 2,4-dinitrophenyl phosphate (pKa of the phenol 4.09) is hydrolyzed far faster than the monoanion 2-chloro-4-nitrophenyl phosphate represents an intermediate case (pKa of the phenol 5.45)6S). 

A kinetic isotope effect 160/180 of 2% in the spontaneous hydrolysis of the 2,4-dinitrophenyl phosphate dianion, whose ester oxygen is labeled, suggests a P/O bond cleavage in the transition state of the reaction, and thus also constitutes compelling evidence for formation of the metaphosphate 66,67). The hydrolysis behavior of some phosphoro-thioates (110) is entirely analogous 68). 

Doubts have recently been expressed regarding the validity of the metaphosphate pathway for hydrolysis of the monoanion of 2,4-dinitrophenyl phosphate (111) 70,71,72) since the basicity of the 2,4-dinitrophenolate group is insufficient to produce a zwitterion corresponding to 106 or even a proton transfer via intermediates of type 103 or 105 (pKa values in water 4.07 for 2,4-dinitrophenol, 1.0 and 4.6 for 2,4-dinitrophenyl phosphate). Instead, hydrolysis and phosphorylation reactions of the anion 111 are formulated via oxyphosphorane intermediates according to 114. 

Yet another situation is observed in the 2,4-dinitrophenyl phosphate dianion. A significant effect of amines on the rate of decomposition is admittedly observed however, typical 2nd order kinetics, lower enthalpy of activation compared with spontaneous hydrolysis, and strongly negative AS values (see Table 3) indicate an Sn2(P) reaction. Surprisingly, the reaction rate remains unaffected by the basicity of the amine, even when its pKa value changes by 8 units. 

Reactions of 2,4-dinitrochloro-benzene and -naphthalene are speeded by DDDAOH and the corresponding chloride -I- NaOH (Cipiciani et at., 1984). The rate/surfactant concentration profiles and the rate constants are very similar to those for reactions in solutions of the corresponding C16 single chain surfactants which form normal micelles. The spontaneous hydrolysis of 2,4-dinitrophenyl phosphate dianion is also speeded by DDDAC1 and rates reach plateau values in very dilute surfactant (Savelli and Si, 1985). 

J Steffans et al., 1973, 1975. The reference reaction is the attack of the anion of a carboxylic acid of pK, 3.91 on methyl 2,4-dinitrophenyl phosphate at 39° (Kirby and Younas, 1970). The intramolecular reaction is corrected for the better leaving group using y LO=1.26 (Khan et al., 1970), and to 39° using the activation energy measured for the intermolecular reaction with acetate (Kirby and Younas, 1970). 

Ibe principle found for zinc(II) was applied to ) complex models by Young et al. (25). The hydroxyl function of copper complex 27a deprotonates with a p value of 8.8 to yield 27b, which cleaves phosphodiester bis(2,4-dinitrophenyl) phosphate (BDP ) by transesterification to produce 28 ( (BDP ) = 7.2 x -1 M-1sec-1 at 25°C see Scheme 5). The analogous complex with a hydroxyethyl pendent cleaves the diester predominantly by hydrolysis, which suggests that the reactive species is not Cun-alkoxide, but —OH-. The rate A(BDP") of... 

Fig. 2. pH-rate profiles for three representative esters at 39°C, ionic strength 1.0, on adjusted scales. A, x I07 min for 2,4,6-trichlorophenyl phosphate , Ahyd x 10 min-1 for 2-chloro-4-nitrophenyl phosphate O, byd x I04 min- for 2,4-dinitrophenyl phosphate. 

Fig. 3. Bronsted plot for the reactions of substituted pyridines with the dianion of 2.4-dinitrophenyl phosphate. The line, which is taken from the corresponding plot for the monoanions, is included...

The kinetics of the hydrolysis of di(2,4-dinitrophenyl) phosphate (DDNPP) were studied in basic solutions buffered with Bis-Tris propane (BTP) in the presence of La3+, Sm3+, Tb3+, and Er3+. Two equivalents of the 2,4-dinitrophenolate ion were liberated for each equivalent of DDNPP and the reaction showed first-order kinetics. Potentiometric titrations showed the formation of dinuclear complexes such as [Ln2(BTP)2(OH) ](6 " i, with values of n varying as a function of pH for all studied metals. Hence the catalytic effect depends on the formation of dinuclear lanthanide ion complexes with several hydroxo ligands.97... 

Fig. 4. Relation between reaction rate and micelle concentration at pH 9-0 and 25-0° (equation 10a) , 1-8 x 10 5 M 2,6-dinitrophenyl phosphate O, 9-4 x 10 M 2,6-dinitro-phenyl phosphate , 6-3 x 10 m 2,4-dinitrophenyl phosphate. For 2,6-dinitrophenyl phosphate n = i, and for 2,4-dinitrophenyl phosphate n = 5 (Bunton et al., 1968).

A detailed study of the specific rates of solvolysis of N,N,N, N -tetra-methyldiamidophosphorochloridate (80) (TMDAPC) with analysis in terms of the extended Grunwald-Winstein equation has been reported (Scheme 19). The stereochemistry of nucleophilic attack at tetracoordinate phosphorus was also discussed." The initial reaction of bis (2,4-dinitrophenyl) phosphate (BDNPP) (81) with hydroxylamine involves release of 1 mol 2,4-dinitrophen-oxide ion and formation of a phosphorylated hydroxylamine (82), which reacts readily with further NH2OH, giving the monoester (83). The intermediate (82) also breaks down by two other independent reactions one involves intramolecular displacement of aryloxide ion (83) and the other involves migration of the 2,4-dinitrophenyl group from O to N and formation of phosphorylated 2,4-dinitrophenylhydroxylamine (84) (Scheme 20)." ... 

Although alkaline hydrolysis of monoalkyl or monoaryl phosphates is ordinarily very difficult, 2,4-dinitrophenyl phosphate, 2,4-(N02)2CaH30P03H2, does react with aqueous base, and with cleavage at the phosphorus-oxygen bond. Suggest an explanation for this. 

Linear free-energy relationships (LFER) with monoanionic phosphorylated pyr-idines indicate a loose transition state in which metaphosphate is not an intermediate.16 The hydrolysis of the monoanion of 2,4-dinitrophenyl phosphate is thought to be concerted,39 but the possibility of a metaphosphate intermediate has not been ruled out with esters having less activated leaving groups. A stereochemical study of the hydrolysis of phenyl phosphate monoanion indicates that the reaction proceeds with inversion.21 This result implies either a concerted mechanism, or a discrete metaphosphate intermediate in a pre-associative mechanism. 

P-O bond fission is the usual mode of attack by nucleophiles on phosphodiesters, although there are exceptions. The labile diester methyl-2,4-dinitrophenyl phosphate shows significant amounts of attack at aromatic carbon (nucleophilic aromatic substitution, with loss of methyl phosphate) in competition with attack at phosphorus, most notably with hydroxide and with primary amines.46 Due to the small size of the methyl group it is sterically susceptible to nucleophilic attack in phosphate esters the hydrolysis of the dimethyl phosphate anion occurs almost exclusively by C-O bond fission.4 With larger or less labile leaving groups, even... 

Bunton et al.15 demonstrated catalytic behavior in the spontaneous hydrolysis of 2,4-dinitrophenyl phosphate promoted by alkane a,co-bis(trimethylammonium) bolaphiles. The enhanced rate of hydrolysis followed the greater degree of organization within vesicles from surfactants possessing longer (CX-CY) spacers. Notably, bolaphiles with 12 and 16 methylene spacers did not form micelles, but instead formed small clusters, and showed a lower rate enhancement versus micellizing surfactants. 

The displacement of substituted phenoxide ions from aryl monophosphate monoanions by nicotinamide (Equation 38) has a PLg of -0.95. Reaction of substituted pyridines with 2,4-dinitrophenyl-phosphate monoanion has a 3 of 0.56. Using effective charge data from Scheme 1 construct a combined effective charge map for the... 

Some examples of rate and binding constants for these micelle-assisted reactions are in Table 6. There are very large differences in k j /k y/ for these reactions, but the rate effects on decarboxylation are large and depend upon the charge on the head group. Reaction of 2,4-dinitrophenyl phosphate is often written as generating intermediate metaphosphate ion, but this species is so short-lived that reaction follows an enforced association mechanism (Buchwald and Knowles, 1982). 

The Role of Nucleophile Solvation. The value of = 0 for the reaction of substituted pyridines with 2,4-dinitrophenyl phosphate (76) is puzzling. If the value of is a measure of the amount of the bond formation to the nucleophile in the transition state, this value might be taken to mean that there is no bond formation to the nucleophile in the transition state. This is obviously not the case, because there is a large increase in the rate of disappearance of the phosphate ester with increasing concentration of the nucleophile the reactions follow simple second-order kinetics. 

The answer to this question only became apparent when it was observed that the reactions of substituted quinuclidines with 2,4-dinitrophenyl phosphate, p-nitrophenyl phosphate and phosphorylated pyridine show a decrease in rate with increasing basicity of the attacking quinuclidine (77). These second-order reactions clearly cannot have a negative amount of bond formation with the nucleophile in the transition state, so that this result forced us to think harder about what could cause zero or negative slopes in Br0nsted-type plots against the pK of the nucleophile. 

Buchwald, Friedman and Knowles succeeded in preparing 2,4-dinitrophenyl phosphate in which the three free oxygen atoms on phosphate were labeled stereospecifically with different isotopes of oxygen. Solvolysis of this compound in methanol and analysis of the methyl phosphate product showed that the reaction had proceeded with inversion of configuration at phosphorus (79). This remarkable experiment supports a concerted bimolecular displacement mechanism, with no metaphosphate intermediate, for the solvolysis of 2,4-dinitrophenyl phosphate in methanol. However, it does not rigorously exclude a stepwise mechanism in which a metaphosphate intermediate with a very short lifetime is formed and reacts with methanol faster than it rotates, and it does not provide direct evidence for a bimolecular, concerted reaction with solvent water. 

Figure 2. Correlation of the rate constants for the reaction of nucleophilic reagents with phosphorylated y-picoline monoanion and methyl 2,4-dinitrophenyl phosphate monoanion. The line has a slope of 0.51 (79).

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