In the light of the current UK-Russia events, how difficult is to synthesize Novichok agents (with known structures)? Is it something that can be made at any well-equipped university and/or chemical factory, or does it involve some very specialized or possibly secret knowledge?
According to Fragmentation pathways and structural characterization of organophosphorus compounds related to the Chemical Weapons Convention by electron ionization and electrospray ionization tandem mass spectrometry Rapid Commun. Mass Spectrom. 2016, 30, 2585–2593:
N-[Bis(dimethylamino)methylidene]-P-methylphosphonamidic fluoride (3) was synthesized by the controlled addition of N,N,N′,N′-tetramethylguanidine to a solution of methylphosphonic difluoride (1). N,N,N′,N′-Tetramethylguanidine (0.60 mmol) and triethylamine (0.65 mmol) in dichloromethane (DCM) (500 μL) were added slowly into the solution of methylphosphonic difluoride (0.40 mmol) in DCM (500 μL), while stirring at 0–5 °C. After 30 min, the resulting precipitate was filtered off and the solution was analyzed by GC/MS.
The corresponding O-alkyl N-[bis(dimethylamino)-methylidene]-P-methylphosphonamidates 4 were synthesized by the addition of ROH to a solution of cpd 3. Sodium hydride powder (NaH, 60% in mineral oil, 0.5 mmol) was washed with dry hexane twice. The hexane was removed and DCM (500 μL) was added and the solution was kept stirring at 0–5 °C. The appropriate alcohol (0.5 mmol) was slowly added into the suspension and the reaction solution was stirred at 0–5 °C for 30 min. Compound 3 in DCM (200 μL) was then added dropwise to the solution, while stirring at 0–5 °C for 2 h. Any precipitate was filtered off and the resulting solutions of the end product were analyzed by GC/MS. It should be noted that, due to the extreme toxicity of these materials, the separation and purification of CWC-related chemical are very difficult and therefore should be carried out only by a trained professional in an efficient fume cupboard equipped with an active charcoal filtration system.