Monoanions hydrolysis reactions

Grzyska PK, Czyryca PG, Purcell J, Hengge AC. Transition state 42. differences in hydrolysis reactions of alkyl versus aryl phosphate monoester monoanions. J. Am. Chem. Soc. 2003 125 13106-13111. 

A comprehensive study has been made of the hydrolysis reactions of jn-nitrophenyl phosphate (143) and its thio analogue, /2-nitrophenyl phosphorothioate (144). Solvent effects, pH-rate profiles, and the effects of divalent metal ions were examined and the results permitted a detailed comparison of the mono- and di-anions of each compound. For example, at 30 °C the ratio of the rate constants of monoanion hydrolysis for the thio analogue and the oxa compound is 1380 1." Mechanistic studies of the acid hydrolysis of 0,0-dimethyl S-(2-methylamino)-2-oxoethyl phosphorodithioate (145) have been reported. "... 

Phosphate esters have a variety of mechanistic paths for hydrolysis. Both C-O and P-0 cleavage are possible depending on the situation. A phosphate monoanion is a reasonable leaving group for nucleophilic substitution at carbon and so 8 2 or SnI reactions of neutral phosphate esters are well known. PO cleavage can occur by associative (by way of a pentacoordinate intermediate), dissociative (by way of a metaphosphate species), or concerted (avoiding both of these intermediates) mechanisms. 

The pronounced proclivity of phosphoric monoester monoanions to eliminate POf is not always recognizable from the characteristic pH profile of Fig. 1. The hydrolysis rate maximum at pH w 4 may be masked by a faster reaction of the neutral phosphoric ester, as in the case of a-D-glucose 1-phosphate63) or on hydrolysis of monobenzyl phosphate 64). In the latter case, the known ability of benzyl esters to undergo SN1 and SN2 reactions permits fast hydrolysis of the neutral ester with C/O bond breakage. The fact that the monoanion 107 of the monobenzyl ester is hydrolyzed some 40 times faster than the monoanion 108 of the dibenzyl ester at the same pH again evidences the special hydrolysis pathway of 107, rationalized by means of the metaphosphate hypothesis. 

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. 

The highly electrophilic character of the POf ion would suggest a very unselective phosphorylation behavior. For example, the ratio of alkyl phosphate to inorganic phosphate obtained in hydrolyses of phosphoric esters in water/alcohol mixtures should reflect the molar ratio of water and alcohol. This is indeed found in numerous cases, e.g. in the hydrolysis of phenyl and 4-nitrophenyl phosphate monoanions 97) or of 4-nitrophenyl phosphate dianions 65) at 100 °C in methanol/ water mixtures of various compositions, as also in the solvolysis of the acetyl phosphate dianion at 37 °C 97) or of phosphoenol pyruvate monoanions 82). Calculations of the free energy of the addition reactions of water and ethanol to the POf ion support the energetic similarity of the two reactions 98) (Table 4). 

Though EM ratios are given for both reactions, the data are not independent. The EM s for the amide hydrolysis are based on a value (EM = 5.1 x 104 M) for the succinamic acid reaction which is assumed to be identical with that for the hydrolysis of monophenyl succinate monoanion. However, both sets of data show similar behaviour. The EM s for the rate processes, initially smaller by less then an order of magnitude than those for equilibrium anhydride formation, increase much less rapidly with increasing methyl substitution, so that the EM ratios decrease with increasing EM. 

In 17, X may be POj (but COCH3, SO3 and other groups have also been examined by this means). In the type of structure shown in 18 we have already encountered the 2-nitrile hydrolyses. With X = POf in 18, divalent metal ions show a pronounced catalysis of the hydrolysis of the dianionic species. The metal is strongly chelated to the phenanthroline but in the product it is unlikely that the 0 is coordinated since a four-membered ring would result (see Sec. 6.8). The monoanionic form (X = POjH ) is the reactive species (Prob. 3). Reaction of the dianion in the absence of metal ion cannot be observed and with Cu +, for example, accelerating effects of >10 are estimated. ... 

Correlation of the observed rates with the concentrations of the substrate species (10) indicates that the metal ion does not catalyze the hydrolysis of the monoanionic form of salicyl phosphate. Combination of the monoanionic form of the substrate with the vanadyl ion would result in an unreactive complex having a neutral carboxyl group. Shift of the proton to the phosphate group could not take place in accordance with the requirements of the general reaction mechanism illustrated in Figure 3. Thus the vanadyl ion would be expected to catalyze the hydrolysis of only the di- and trinegative forms of the substrate. 

Proton transfer may proceed directly or via a six-membered cyclic transition state involving a molecule of water. A calculation of the intermediate zwitter-ionic concentration for the hydrolysis of methyl phosphate monoanion, based on the pKa values for methanol and methyl phosphate dianion, predicts the first-order rate coefficient for zwitterion decomposition to be ca. 10 sec-1 at 100°C. This value is in good agreement with the observed rate of hydrolysis and, considering the assumptions involved, with the rate of P-O bond fission of the presumed zwitterionic intermediate (2) formed in the Hg(II) catalyzed solvolysis of phosphoenolpyruvic acid, a model reaction for pyruvate kinase10. 

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