Dinitrophenyl phosphates, hydrolysis

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). 

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... 

With few exceptions the dianions of monoalkyl and monoaryl phosphates are unreactive but with a good leaving group, e.g. carboxylate, dianions undergo hydrolysis. The same reasoning applies to a dinitrophenoxide anion and the pH-rate profile for the hydrolyses of 2,4- and 2,6-dinitrophenyl phosphates differs from those of other aryl phosphates in that the dianion is more reactive than the monoanion species (Fig. 2)22-23. This reactivity is at-... 

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... 

Cationic surfactants with an electron rich phenyl substituent on the hydrophilic ammonium head group (phenyl, 2,4-dimethoxyphenyl, and 2,4-dimethoxybenzyl dimethylammonium bromides) were found to be more efficient catalysts than CTAB for the hydrolysis of 2,4- and 2,6-dinitrophenyl phosphates (Bunton et al., 1970). The pseudo-first order rate constants increased appreciably at low concentrations of these... 

The electrostatic model for the micellar effect on the hydrolysis of phosphate monoesters is also consistent with the results of inhibition studies (Bunton et al., 1968, 1970). The CTAB catalyzed hydrolysis of the dinitrophenyl phosphate dianions was found to be inhibited by low concentrations of a number of salts (Fig. 9). Simple electrolytes such as sodium chloride, sodium phosphate, and disodium tetraborate had little effect on the micellar catalysis, but salts with bulky organic anions such as sodium p-toluenesulfonate and sodium salts of aryl carboxylic and phosphoric acids dramatically inhibited the micelle catalysis by CTAB. From equation 14 and Fig. 10, the inhibitor constants, K, were calculated (Bunton et al., 1968) and are given in Table 9. The linearity of the plots in Fig. 10 justifies the assumption that the inhibition is competitive and that incorporation of an inhibitor molecule in a micelle prevents incorporation of the substrate (see Section III). Comparison of the value of for phenyl phosphate and the values of K for 2,4-and 2,6-dinitrophenyl phosphates suggests that nitro groups assist the... 

Fig. 10. Effect of inhibiting salts upon the hydrolysis of 2,6-dinitrophenyl phosphate in 3 X lO- MCTABat 25-0° and pH 9 0 A, sodium chloride .sodium methane sulfonate I. sodium P toluene sulfonate O. sodium benzoate . dipotassium phthalate o. disodium terephthalate disodium phenyl phosphate (Bunton et al., 1968).

Robinson, 1969a). It is probable that the hydrophobic nature of the phenyl groups of p-nitrophenyl diphenyl phosphate results in deep penetration of the neutral ester in the Stern layer, thus shielding the phosphoryl group from nucleophilic attack. Unlike other reactions between nucleophiles and neutral substrates catalyzed by cationic micelles (Bunton and Robinson, 1968, 1969a) and the hydrolysis of dinitrophenyl phosphate dianions in the presence of cationic micelles (Bunton et al., 1968), the catalysis of the hydrolysis of -nitrophenyl diphenyl phosphate by CTAB arises from an increase in the activation entropy rather than from a decrease in the enthalpy of activation. The Arrhenius parameters for the micelle-catalyzed and inhibited reactions are most probably manifestations of the extensive solubilization of this substrate. However, these parameters can be composites of those for the micellar and non-micellar reactions and the eifects of temperature on the micelles themselves are not known. Interpretation of the factors which affect these parameters must therefore be carried out with caution. In addition, the inhibition of the micelle-catalyzed reactions by added electrolytes has been observed (Bunton and Robinson, 1969a Bunton et al., 1969, 1970) and, as in the cases of other anion-molecule reactions and the heterolysis of dinitrophenyl phosphate dianions, can be reasonably attributed to the exclusion of the nucleophile by the anion of the added salt. 

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. 

Zinc complexes of the cyclen ([12]aneN4 = 1,4,7,10-tetraazacyclododecane) ligand have been extensively studied in terms of phosphate ester hydrolysis reactivity. For example, a proposed binuclear Zn(II) hydroxide complex of cyclen was reported to enhance the rate of hydrolysis of ethyl(2,4-dinitrophenyl)-methylphosphonate and diethyl(2,4-dinitrophenyl) phosphate.223,224 It should be noted that the nuclearity of the zinc-cyclen complex in solution was not conclusively identified in this work. 

Gorenstein and co-workers have used primary 0 isotope effects to study the structure of the transition state in the hydrolysis of 2,4-dinitrophenyl phosphate in which the bridging ester oxygen is labeled with 0 (47). The results of 32 determinations were averaged to reveal an isotope effect of 1.0204 + 0.0044. 

Solvolyses of Phosphoric Acid Derivatives.—The solvolysis of organic phosphates has been reviewed. A significant 0 isotope effect was observed in the solvolysis of the dianion of 2,4-dinitrophenyl phosphate, and since no such isotope effect is observed in the alkaline solvolysis of the dibenzyl ester this has been adduced as evidence for a monomeric metaphosphate elimination in the former case. The nucleophilic attack of hydroxide ion on bis-(2,4-dinitrophenyl) phosphate is inhibited by micelles of non-anionic detergents and this is attributed to binding of the substrate. Hydrolysis of 3,4-dimethoxyphenyl phosphate proceeds by way of the monoanion, the neutral molecule, and the conjugate acid, and is thus in accord with earlier results on other methoxyphenyl phosphates. ... 

Bunton et al. proved that alkane a, -bis(tri-methylammonium) bolaphiles catalyze the spontaneous hydrolysis of 2,4-dinitrophenyl-phosphates. [11] The rate of hydrolysis was enhanced by micellar bolaphiles this rate enhancement followed the greater organiza-... 

Ramirez, le Noble and coworkers (Ramirez et al., 1986) measured the volume of activation for the hydrolysis of 2,4-dinitrophenyl phosphate and found that the reaction is accelerated by pressure. The expectation for a dissociative process is that there will be a reduction in rate caused by an increase in pressure since the rate-determining step is expansive. In comparison, a reaction that proceeds by nucleophilic addition involves shrinkage and should be aided by pressure. Thus the experiment supports a concerted mechanism. 

The effects of four cobalt(III) complexes [Co(trien)(OH)(OH2)] , [Co(en)2(OH)(OH)2]"-", [Co(dien)(OH)(OH2)2] ", and [Co(en)2(OH)(NH3)] -" on the rate of hydrolysis of bis(p-nitrophenyl)phosphate, p-nitrophenyl phosphate, and bis(2,4-dinitrophenyl)phosphate have been examined at 50 under neutral pH conditions. At pH 7 the cobalt-bound phosphodiester [Co(en)2(OH)[OP(0)-(0C6H4N02)2] is cleaved 10 times more rapidly (2.7 x 10 s" ) than the unbound phosphodiester, while the cobalt-bound phosphomonoester is cleaved only 10" times more rapidly. The reactivity of the cobalt complexes is [Co(trien)(OH)-... 

Again, kinetic results indicate rate-determining bimolecular attack of water in transition-state formation in hydrolysis of di(2,4-dinitrophenyl)phosphate in acid or neutral solution. The variation of rates of hydrolysis of phenyl bischloromethylphosphinate (14) with solvent composition in aqueous sulphuric acid suggests the participation of two water molecules in the transition state, which would thus contain six-co-ordinated phosphorus. ... 

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