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Stereochemical Inversion of Phosphonothioate Methanolysis by La(III) and Zn(II): Mechanistic Implications for the Degradation of Organophosphate Neurotoxins

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journal contribution
posted on 02.01.2012, 00:00 by Louis Y. Kuo, Sara K. Glazier
The utility of phosphonothioate methanolysis to degrade organophosphate neurotoxins has prompted the stereochemical investigation of this useful transformation. The methanolysis of enantiomerically pure O,S-diethyl phenylphosphonothioate (5) was studied both in the presence and in the absence of metal ions known to catalyze the phosphonothioate → phosphonate transformation. This report outlines the syntheses of enantiomerically pure 5 and its methanolysis product O-ethyl O-methyl phenylphosphonate (7). Compound 7 results from exclusive P–S scission of 5, which is the desired mode of phosphonothioate methanolysis (Ea = 14.5 ± 0.5 kcal/mol). The stereochemical analysis of the phosphonothioate methanolysis was done for the first time with β-cyclodextrin, and it shows complete inversion on the phosphorus center upon methoxide displacement of ethanethiolate. The presence of La­(III) or Zn­(II) complexes do not alter this SN2-like substitution which sheds new light on the mechanism of methanolysis of phosphonothioates.