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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.

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The degradation of obidoxime chloride (toxogonin), a reactivator of inhibited cholinesterase in organophosphorus poisoning, in concentrated (250 mg mL(-1)) acidic solutions was studied by HPLC at several temperatures to determine the degradation mechanism. The degradation had an autocatalytic profile, which was found to result from the formation of formaldehyde during the degradation process. The activation energy of the hydrolysis was 26.2 kcal mol(-1). The shelf-life (t90, the time by which 10% of the drug has degraded) at 25 degrees C was calculated by several methods and found to be more than 37 years. Autocatalysis, a mechanism found only rarely in the degradation of pharmaceuticals, has not been reported in previous studies of obidoxime hydrolysis.

The behavior of phenyl hydrogen α-hydroxyiminobenzylphosphonate (E )-2 in aqueous hydrochloric acid solution was examined by 31 P NMR spectroscopy and by HPLC. Compound (E )-2 was found to undergo two competing acid-catalyzed reactions. 1) Fragmentation to phenyl phosphate (6) and benzonitrile, similar to the fragmentation of other hydroxyiminophosphonates to metaphosphate examined previously. The fragmentation of (E )-2 was found to be slower by a factor of 4 than that of hydrogen methyl α-hydroxyiminobenzylphosphonate ((E )-1). This phenomenon is interpreted in terms of inductive effects on the suggested metaphosphate intermediate. 2) Compound (E )-2 was found to undergo hydrolytic cleavage of the oxime group giving NH 2 OH and hydrogen phenyl benzoylphosphonate (4), which was found to hydrolyze to phenol and benzoylphosphonic acid ( 5). The latter reacted with the NH 2 OH liberated in the previous step to give α-hydroxyiminobenzylphosphonic acid ((E )-3), which fragmented to benzonitrile and phosphoric acid. The rate of a possible hydrolysis of the phenol group in oxime (E )-2 was shown to be slower by two orders of magnitude than that from ketone 4. This phenomenon is interpreted in terms of acid mediated retardation of acid catalyzed hydrolysis of phenol due to initial protonation of the oxime nitrogen in (E )-2.