Isopropyl methylphosphonofluoridate

FLUORINECOMPOUNDS,INORGANIC - PHOSPHORUS] (Vol 11) Sarin. (See also Isopropyl methylphosphonofluoridate.)... 

Diisopropyl methylphosphonate is an organophosphate compound that was first produced in the United States as a by-product of the manufacture of the nerve gas isopropyl methylphosphonofluoridate (GB, or Sarin) (ATSDR 1996 EPA 1989 Robson 1977, 1981). It is not a nerve gas and is not a metabolite or degradation product (Roberts et al. 1995). Diisopropyl methylphosphonate constitutes approximately 2-3% of the crude GB product, but it is neither a metabolite nor a degradation product of GB (EPA 1989 Rosenblatt et al. 1975b). Diisopropyl methylphosphonate is not normally produced except for its use in research. One method of producing diisopropyl methylphosphonate is to combine triisopropyl phosphite and methyl iodide. The mixture is then boiled, refluxed, and distilled, yielding diisopropyl methylphosphonate and isopropyl iodide (Ford-Moore and Perry 1951). Diisopropyl methylphosphonate may also be prepared from sodium isopropyl methylphosphonate by a reaction at 270° C, but a portion of the resulting diisopropyl methylphosphonate is converted to trimethylphosphine oxide at this temperature (EPA 1989). 

Sarin (isopropyl methylphosphonofluoridate), called GB in the United States, is a volatile substance taken up mainly through inhalation. 

DOT MARKING Poisonous liquid, n.o.s. (Isopropyl methylphosphonofluoridate) UN2810... 

This ester, isopropyl methylphosphonofluoridate (X), is a colourless liquid. It is more toxic than D.F.P., but shows very similar physiological properties, intense myosis, respiratory collapse, powerful anticholinesterase activity, etc. The liquid passes rapidly through the skin. At the end of World War II, two plants were under construction in Germany for the production of the material on a large scale. 

Nerve agents are organophosphonate compounds. They contain phosphorus double-bonded to an oxygen atom and single-bonded to a carbon atom. GB is O-isopropyl methylphosphonofluoridate. VX is O-ethyl-S [2-(diisopropyl amino) ethyl]-methylphospho-nothiolate. 

A hydroxoaqua copper complex containing N, N, N, A -tetramethyl-1,2-diamino-ethane (250) is an excellent catalyst for the hydrolysis of sarin, O-isopropyl methylphosphonofluoridate (251), and diethyl p-nitrophenyl phosphate (252 R = Et). The mechanism of the reaction probably involves bound hydroxide attacking the phosphoryl group with concomitant electrophilic catalysis by copper. 

Hackley, B.E., Jr., Steinberg, G.M., Lamb, J.C. 1959. Formation of potent inhibitors of AChE by reaction of pyrldinaldoxlmes with isopropyl methylphosphonofluoridate (GB). Arch. Blochem. 

Studies of the in vitro reaction between the alkaline oximes and sarin (isopropyl methylphosphonofluoridate, GB) revealed that 2-PAM reacted rapidly with the organophosphorus ester in solution at physiologic pH and temperature (Figure 2-2)... 

Methylphosphonic acid (MPA), a degradation product of gas chemical warfare agents, such as sarin (isopropyl methylphosphonofluoridate), soman or VX (0-ethy I -.S -2-di isopropyl am i noethvl methyl phosphonoth ioate), has been recognized selectively by an MIP chemosensor using potentiometric transduction (Table 6) [181]. The MIP preparation involved co-adsorption, in ethanol, of the methylphosphonic acid (MPA) template and octadecyltrichlorosilane, followed by silanization on the indium-tin oxide (ITO) electrode surface in the chloroform-carbon tetrachloride solution at 0 °C. Subsequently, the electrode was rinsed with chloroform to remove the template. A potential shift due to the presence of MPA was significant as compared to that due to interferants like methyl parathion, dimethoate, phosdrin, malathion, etc. The linear concentration range varied from 50 pM to 0.62 M MPA at LOD as low as 50 pM and an appreciably short response time of 50 s. 

Shiloff, J.D., Clement, J.G. (1987). Comparison of serum concentration of the acetylcholinesterase oxime reactivatiors HI-6, obidoxime and PAM to efficacy against sarin (isopropyl methylphosphonofluoridate) poisoning in rats. Toxicol. Appl. Pharmacol. 89 278-80. 

The G-nerve agents include GA (tabun, ethyl A,A-dimethyl-phosphoramidocyanidate), GB (sarin, isopropyl-methylphosphonofluoridate), GD (soman, 1,2,2-tri-methylpropyl methylphosphonofluoridate), and VX (o-ethyl 5-[2-(diisopropylamino)ethyl] methylphosphonothiolate). The V-type nerve agents are several orders of magnitude less volatile than the G-type agents and act primarily as a liquid via the percutaneous route for example, VX is several orders of magnitude more lethal percutaneously than sarin (Reutter, 1999). 

Nerve agents Also known as anticholinesterase agents, are chemical compounds that inhibit the ability of cholinesterase to hydrolyze acetylcholine, which is essential to mediation of neurotransmitter function in nerve impulses. Nerve agents include VX (0-ethyl S-(2-dusopropylaminoethyl) methylphospho-nothioate) and the G-series agents tabun (GA)-dimethylphosphoramido-cyanidate, sarin G -isopropyl methylphosphonofluoridate and soman (GD)-Pinacolyl methyl phosphonofluoridate. 

GB, isopropyl methylphosphonofluoridate and related compounds (Hazardous Waste Code NOOl) ... 

Boter, H.L., Ooms, A.J.J., Van Den Berg, G.R., and Van Dijk, C. 1966. The synthesis of optically active isopropyl methylphosphonofluoridate (Sarin). Recueil des travaux chimiques des Pays-Bas, 85 147-150. 

Gustafson, R.L. and Martell, A.E. 1962. A kinetic study of the copperfll) chelate-catalyzed hydrolysis of isopropyl methylphosphonofluoridate (Sarin). Journal of the American Chemical Society, 84 2309-2316. 

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