Quantum mechanical calculations on the reaction of ethoxide anion with O,S-dimethyl methylphosphonothiolate

Density functional and correlated ab initio molecular orbital calculations have been carried out in an effort to understand the reaction of ethoxide with O,S-dimethyl methylphosphonothiolate, a model compound for the potent chemical warfare agent VX. The results clearly indicate that ethoxide will preferentially attack opposite the more apicophilic methoxide ligand but that ensuing pseudorotations of the initial trigonal bipyramidal intermediate will lead to both P-O and P-S bond cleavage processes. However, the P-O cleavage pathway is found to be reversible and slightly endothermic while the P-S cleavage pathway is irreversible and highly exothermic. Under equilibrating conditions, the reaction will therefore lead to exclusive formation of the P-S bond cleavage products, making ethoxide a potentially useful nucleophile for the detoxification of VX. (c) 2007 Elsevier B.V. All rights reserved.