Benzyl trichloroacetimidates as derivatizing agents for phosphonic acids related to nerve agents by EI-GC-MS during OPCW proficiency test scenarios

Subramanian, Alagu; Rosales, José A.; Leif, Roald N.; Valdez, Carlos A.

doi:10.1038/s41598-022-25710-4

Title: Benzyl trichloroacetimidates as derivatizing agents for phosphonic acids related to nerve agents by EI-GC-MS during OPCW proficiency test scenarios

Journal Article · Fri Dec 09 00:00:00 EST 2022 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-022-25710-4· OSTI ID:1902764

Subramanian, Alagu; Rosales, José A.; Leif, Roald N.; Valdez, Carlos A.

Abstract The use of benzyl trichloroacetimidates for the benzylation of phosphonic acid nerve agent markers under neutral, basic, and slightly acidic conditions is presented. The benzyl-derived phosphonic acids were detected and analyzed by Electron Ionization Gas Chromatography–Mass Spectrometry (EI-GC–MS). The phosphonic acids used in this work included ethyl-, cyclohexyl- and pinacolyl methylphosphonic acid, first pass hydrolysis products from the nerve agents ethyl N -2-diisopropylaminoethyl methylphosphonothiolate (VX), cyclosarin (GF) and soman (GD) respectively. Optimization of reaction parameters for the benzylation included reaction time and solvent, temperature and the effect of the absence or presence of catalytic acid. The optimized conditions for the derivatization of the phosphonic acids specifically for their benzylation, included neutral as well as catalytic acid (< 5 mol%) and benzyl 2,2,2-trichloroacetimidate in excess coupled to heating the mixture to 60 °C in acetonitrile for 4 h. While the neutral conditions for the method proved to be efficient for the preparation of the p -methoxybenzyl esters of the phosphonic acids, the acid-catalyzed process appeared to provide much lower yields of the products relative to its benzyl counterpart. The method’s efficiency was tested in the successful derivatization and identification of pinacolyl methylphosphonic acid (PMPA) as its benzyl ester when present at a concentration of ~ 5 μg/g in a soil matrix featured in the Organisation for the Prohibition of Chemical Weapons (OPCW) 44th proficiency test (PT). Additionally, the protocol was used in the detection and identification of PMPA when spiked at ~ 10 μg/mL concentration in a fatty acid-rich liquid matrix featured during the 38 ^th OPCW-PT. The benzyl derivative of PMPA was partially corroborated with the instrument's internal NIST spectral library and the OPCW central analytical database (OCAD v.21_2019) but unambiguously identified through comparison with a synthesized authentic standard. The method’s MDL (LOD) values for the benzyl and the p -methoxybenzyl pinacolyl methylphosphonic acids were determined to be 35 and 63 ng/mL respectively, while the method’s Limit of Quantitation (LOQ) was determined to be 104 and 189 ng/mL respectively in the OPCW-PT soil matrix evaluated.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1902764

Alternate ID(s):: OSTI ID: 2008189

Report Number(s):: LLNL-JRNL-841699; 21299; PII: 25710

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Vol. 12 Journal Issue: 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Analytical chemistry
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phosphonic acid
benzylation
trichloroacetimidates

Title: Benzyl trichloroacetimidates as derivatizing agents for phosphonic acids related to nerve agents by EI-GC-MS during OPCW proficiency test scenarios

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