Fragmentation of methyl hydrogen α-hydroxyiminobenzylphosphonates — kinetics, mechanism and the question of metaphosphate formation †

Abstract

The thermodynamics, pH dependency and solvent effects of the fragmentation reaction of a series of α-oxyiminobenzylphosphonate monomethyl esters [(E)-1a-f ] were examined in water and other hydroxylic solvents by UV and by 31 P NMR spectroscopy at pH 0-3.1. The fragmentation of compounds (E)-1a-f was found to be a first-order reaction in substrate over the acidity range studied, while the dependence on the acidity is more complex, with rate constants k 1 and k 2 . The ρ values corresponding to the first and second order rate constants were Ϫ1.12 and Ϫ0.835, respectively, indicating that the reaction is facilitated by electron-donating substituents, which probably enhance the protonation of the oxime OH group. Activation parameters for k 1 and k 2 reactions were also calculated. The nearzero values of the entropies of activation obtained are consistent with a dissociative transition state with almost no bonding to a nucleophilic solvent. Monitoring the fragmentation reaction of (E)-1a in several binary alcohol-water mixtures at different acidities showed that the reaction rate is enhanced by the alcohol's acidity and not hampered by the steric requirements of the alcohol molecule. This rules out in our opinion, the likelihood for nucleophilic solvent assistance in the rate-determining step. On the other hand, product studies show that both the nucleophilicity and the steric requirements of the alcohol are of importance in determining the product formed in the fragmentation of (E)-1a. The highest selectivity (S) value was found for MeOH, while S values of <1 were observed for 2,2,2trifluoroethanol and the sterically hindered alcohols. The divergence between the effects of the solvent on the rate, on the one hand, and on the products on the other, indicates that the rate limiting step and the product determining step do not share a common transition state and that the reaction coordinate includes at least one reactive intermediate, probably methyl metaphosphate. The results are compatible with a dissociative mechanism (D N *A N or D N ϩ A N ), in which the solvating water molecules pull the departing water molecule into the hydration shell, while the solvated phosphonic group becomes a metaphosphate without nucleophilic assistance. The fragmentation of oxyiminobenzylphosphonates to metaphosphate is perceived as a special case of the "abnormal" Beckmann reaction.

Dineopentyl Phosphate Hydrolysis: Evidence for Stepwise Water Attack

“…The central phosphoryl moiety is tending in structure toward a neutral phosphosphate ester, a species that has been implicated in the fragmentation of R-hydroiminophosphonates. 68 This again mirrors the behavior of phosphate monoester monoanions, and suggests a major role for intramolecular general acid catalysis using the phosphoryl OH. Both pathways have identical activation energies, suggesting that when there is a proton available for facile extraction by the departing leaving group, both stepwise and concerted pathways are equally viable.…”

A kinetic study of competing fragmentation and hydrolyses of phenyl hydrogen α-hydroxyiminobenzylphosphonate—a case of acid mediated inhibition of acid catalysis

“…[1][2][3][4][5][6][7][8][9] Recently we published a detailed kinetic investigation of the fragmentation of methyl hydrogen α-hydroxyiminobenzylphosphonate ((E )-1) and some of its derivatives in water and in mixed alcohol-water solutions under acidic conditions. 10 The results were compatible with a dissociative mechanism (D N *A N or D N ϩ A N ). The thermodynamics, and especially the different solvent effects on the fragmentation rate, on the one hand, and on the products on the other, indicated that the rate limiting step and the product determining step do not share a common transition state, and that the reaction coordinate includes at least one reactive intermediate, probably methyl metaphosphate (Scheme 1).…”

“…However, we should expect equilibrium formation of the ketone, PhCOPO(OH)OMe. Assuming that k 4 and k Ϫ4 are similar for (E )-1 and (E )-2 and using Dynafit 18 we can calculate that in the concentration range used for NMR analysis in the case of (E )-1 (around 0.04 M), 10 we should expect to see a maximum of 0.0048 M (12%) of the ketone after 70 min but only an easily unnoticeable 0.002 M (5%) after 5 hours when the reaction was actually checked.…”

Fragmentations and Rearrangements of &#945;-Hydroxyiminoalkylphosphonates

“…More recently, the thermodynamics, pH dependency and solvent effects of this fragmentation reaction was studied on a series of para-substituted -oxyiminobenzylphosphonate monomethyl esters, 38, in water and other hydroxylic solvents [21]. Briefly, the fragmentation reaction requires acidic conditions and there was practically no fragmentation observed above pH 3.…”

“…As an anion, the oxime OH needs not to be considered as a leaving group. The full mechanistic scheme for the hydronium catalyzed and uncatalyzed fragmentation, involving pre-equilibrium formation of the reactive forms, which proceed to products, is described in paper [21]. The only significant sources of fragmentation are the protonated oxime (cation) and the The observed solvent isotope effects, k H /k D ~ 0.6, indicate that the reaction proceeds via specific acid catalysis and that fragmentation of the neutral species is in accord with a pre-equilibrium proton transfer in the ground state.…”