Diisopropyl methylphosphonic acid

Diisopropyl methylphosphonate is a colorless liquid at normal temperatures. It is also known as methyl-,bis-(l-methyl-ethyl)ester, phosphonic acid, and methyl-diisopropyl ester. 

Once inside the body, diisopropyl methylphosphonate is rapidly converted to isopropyl methyl-phosphonic acid (IMPA), which is rapidly cleared from the blood. Laboratory tests can determine the amount of IMP A in the blood or urine. However, because IMPA leaves the body rapidly, these tests are useful only for recent exposure. It is helpful for your doctor to know whether there are other chemicals to which you have been exposed. See Chapters 2 and 6 for more information. 

Diisopropyl methylphosphonate is rapidly absorbed following oral administration in animals and is widely distributed throughout the body. Two metabolites of diisopropyl methylphosphonate are isopropyl methylphosphonic acid (IMPA) and methylphosphonic acid (MPA). Excretion of these metabolites in animals occurs primarily through the urine. 

DIISOPROPYL METHYLPHOSPHONATE (Methanephosphonic acid, diisopropyl ester)... 

A relatively general procedure for the preparation of dialkyl 2-oxoalkylphosphonates by direct acylation of dialkyl 1-lithioalkylphosphonates has been introduced by Corey and Kwiatkowski in 1966. The use of phosphonate carbanions as nucleophiles in reaction with carboxylic esters avoids the problems associated with the Michaelis-Arbuzov reaction. The reaction sequence is initiated by the addition at low temperature of dimethyl 1-lithiomethylphosphonate (2 eq and frequently more) to a carboxylic ester (1 eq) to give the transient lithium phosphonoenolate. The dimethyl methylphosphonate, being readily available and easy to eliminate, is the most frequently used phosphonate, but other phosphonates such as diethyl and diisopropyl methylphosphonates can be used. When the resulting enolate is treated with acid, dimethyl 2-oxoalkylphosphonate is produced in moderate to good yields (45-95%, Scheme 7.20). The reaction has been achieved with... 

Ford-Moore, A.H., and Perry, B.J., Diisopropyl methylphosphonate (Phosphonic acid, methyl-, diisopropyl ester), Org. Synth., 31, 33, 1951 Org. Synth. Coll. Vol. IV, 325, 1963. 

Large amounts of 0-isopropyl methylphosphonic acid were found in blood and nrine of victims of the terrorist attacks with sarin in Matsumoto and Tokyo. Until recently, it was assnmed that hydrolysis of phosphofluoridates in plasma and tissues of mammals proceeds exclusively by cleavage of the P F bond. For example, treatment of C( )P( )- P-soman with rat plasma or liver homogenate did not lead to any conversion of PMPA into the secondary hydrolysis product methylphosphonic acid (MPA). Ramachandran observed that the primary hydrolysis product of DF P, i.e., 0,0-diisopropyl P-phosphoric acid, is not metabolized after s.c. admiiustration to mice. Rather, the product was excreted unchanged into urine. However, Nakajima et al. reported that MPA was detected (in urine) until the third day after hospitalization of a victim of the terrorist attack with sarin in Matsumoto. This discrepancy needs further investigation. 

Kaaijk and Frijlink (1977) and Verweij and Boter (1976) reported on the degradation (presumably by all processes) of VX in soil under laboratory conditions. Degradation was rapid with formation of ethyl methylphosphonic acid and diisopropyl ethyl mercaptoamine. After 1 d, the applied concentration of 0.2 mg/g soil decreased to 22% in humic sand and 2% in humic loam and clayey peat. Only 0.1% of applied VX was detectable in all soils after 3 wk. The half-life of ethyl methylphosphonic acid was 8 d the degradation product was methyl phosphonic acid. Binding of the metabolites but not the parent compound correlated positively with the amount of organic matter in the soil. Small (1984)... 

In the same study, droplets of GB deposited on the snow surface were removed by a combination of evaporation, which was dependent on wind speed, and hydrolysis. Within 5 hr, approximately 55% was removed by evaporation and 15% was removed by hydrolysis. Newly fallen snow protected droplets from evaporation. However, 2 and 4 wk after being sprayed on the snow, GB was still present. The hydrolysis product, isopropyl methylphosphonic acid, as well as the impurities diisopropyl methylphosphonate and dipinacolyl methyl-phosphonate were present, even after 4 wk. 

Fig. 3 Reversed-phase HPLC-MS/MS chromatogram using formic acid in the mobile phase and an Atlantis dC18 column. The standard mixture of alkyl phosphonic acids with a concentration of 10 p,g/ml each was detected using multiple reaction monitoring (MRM) 1) methylphosphonic acid (MPA, miz 96.8 78.7) 2) ethyl methylphosphonic acid (EMPA, mIz 125 96.8) 3) C>-elhyl A,A-dimethylamidophosphoric add (EDMAPA, miz 154.2—>126) 4) isopropyl methylphosphonic acid (iPrMPA, nJz 139.1 %.8) 5) pinacolyl methylphosphonic acid (PinMPA, miz 181.3- 96.8) 6) diisopropyl methylphosphonic add (DiPrMPA, mk 181.3 139.1). See the text for further chromatogr hic details and the MS/MS conditions used.

CS = Ortho-chlorobenzalmalononitrile MMSA = Methane methyl sulfonic acid MPA = Methylphosphonic acid DIMP = Diisopropyl methylphosphonate IPMP = Isopropyl methylphosphonic acid Found in subsequent review of data. 

New types of acyclic nucleoside phosphonates (408-412) have been obtained using a multistep synthetic approach based on N-1, O- and S-alkylations of 4-and 2,4-substituted 6-hydroxy and 6-mercaptopyrimidines with diisopropyl 2-(chloroethoxy)methylphosphonate and (R) or (S) - [2-(diisopropylphos-phonyl)methoxy] propyl tosylate. Inhibitory activity against viruses of both the nucleoside phosphonates and the related phosphonic acids was investigated. It was found that the 6[2-(phosphonomethoxy)ethoxy]pyrimidines must bear an (unsubstituted) amino group concomitantly on both C-2 and C-4, or an amino on C-2 and an OH group on C-4, to display antiviral activity. Alkyl ethers are preferred over alkyl thioethers. The compounds of the 6-[2-(phos-phonomethoxy)ethoxy] and 6-[2-(phosphonomethoxy) propoxy]pyrimidine... 

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