Practical Benzylation of N,N‐substituted Ethanolamines Related to Chemical Warfare Agents for Analysis and Detection by Electron Ionization Gas Chromatography–mass Spectrometry

The benzylation of three low molecular weight N,N-disubstituted ethanolamines related to chemical warfare agents (CWAs) to furnish derivatives with improved gas chromatography-mass spectrometry (GC-MS) profiles is described. Due to their low molecular weight and polar nature, N,N-disubstituted ethanolamines are notoriously difficult to detect by routine GC-MS analyses during Organisation for the Prohibition of Chemical Weapons (OPCW) proficiency tests (PTs), particularly in scenarios when they are present at low levels (~1-10 ppm) amidst more abundant interferences. Our studies revealed that the optimal derivatization conditions involved the treatment of the ethanolamine with benzyl bromide in the presence of an inorganic base (e.g., Na2 CO3 ) in dichloromethane at 55°C for 2 h. This optimized set of conditions was then successfully applied to the derivatization of N,N-dimethylethanolamine, N,N-diethylethanolamine and N,N-diisopropylethanolamine present separately at 1 and 10 μg/mL concentrations in a glycerol-rich matrix sample featured in the 48th OPCW PT. The benzylated derivatives of the three ethanolamines possessed retention times long enough to clear the massive glycerol-containing matrix interferences. The protocol herein is introduced as an alternative method for derivatization of these CWA and pharmaceutically important species and should find broad applicability in laboratories where routine forensic analysis is carried out.