Ion−Molecule Reactions of O,S-Dimethyl Methylphosphonothioate: Evidence for Intramolecular Sulfur Oxidation during VX Perhydrolysis

• Published in: Journal of organic chemistry Vol. 74; no. 24; pp. 9319 - 9327
• Main Authors: McAnoy, Andrew M, Williams, Jilliarne, Paine, Martin R. L, Rogers, Michael L, Blanksby, Stephen J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 18-12-2009
• Subjects: Carbon - chemistry; Chemical Warfare Agents - chemistry; Chemical Warfare Agents - toxicity; Chemistry; Exact sciences and technology; Hydrogen-Ion Concentration; Hydrolysis; Ions; Kinetics; Kinetics and mechanisms; Mass spectrometry; Organic chemistry; Organophosphorus Compounds - chemistry; Organothiophosphorus Compounds - chemistry; Organothiophosphorus Compounds - toxicity; Oxidation-Reduction; Phosphorus - chemistry; Protons; Reactivity and mechanisms; Sulfhydryl Compounds - chemistry; Sulfur - chemistry; Reaction intermediate; Phase transfer reaction; Hydrogen Peroxides Anions; Ion molecule reaction; Isotope labelling; Molecular structure; Exothermic reaction; Toxicity; SN2 mechanism; Selectivity; Phosphorus Organic compounds; Organic sulfide; Chemical warfare agent; Anions; Ion trap; Reaction mechanism; Cleavage; Basic medium; Oxidation; Intramolecular reaction; Chemical solution; Nucleophilic reaction; Organic thiophosphonate; Proton transfer; Theoretical study; Experimental study; Hydrolysis; Toxin; Neurotoxin; Kinetics; Gas phase; Nucleophilic addition
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo901944p

The alkaline perhydrolysis of the nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) was investigated by studying the ion−molecule reactions of HOO− with O,S-dimethyl methylphosphonothioate in a modified linear ion-trap mass spectrometer. In addition to simple proton transfer, two other abundant product ions are observed at m/z 125 and 109 corresponding to the S-methyl methylphosphonothioate and methyl methylphosphonate anions, respectively. The structure of these product ions is demonstrated by a combination of collision-induced dissociation and isotope-labeling experiments that also provide evidence for their formation by nucleophilic reaction pathways, namely, (i) SN2 at carbon to yield the S-methyl methylphosphonothioate anion and (ii) nucleophilic addition at phosphorus affording a reactive pentavalent intermediate that readily undergoes internal sulfur oxidation and concomitant elimination of CH3SOH to yield the methyl methylphosphonate anion. Consistent with previous solution phase observations of VX perhydrolysis, the toxic P−O cleavage product is not observed in this VX model system and theoretical calculations identify P−O cleavage to be energetically uncompetitive. Conversely, intramolecular sulfur oxidation is calculated to be extremely exothermic and kinetically accessible explaining its competitiveness with the facile gas phase proton transfer process. Elimination of a sulfur moiety deactivates the nerve agent VX and thus the intramolecular sulfur oxidation process reported here is also able to explain the selective perhydrolysis of the nerve agent to relatively nontoxic products.