Isopropyl methyl phosphonic acid

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. 

US EPA (2005b). Isopropyl methyl phosphonic acid. IRIS online database http //www.epa.gov/ iriswebp/iris/index.html. Washington, DC US Environmental Protection Agency, retrieved April 18, 2005. 

FIGURE 52.1. Metabolic detoxification of warfare nerve agents tabun, sarin, soman, and VX in mammals in vivo. Chemical names of metabolites are EDMPA - ethyl dimethylaminophosphoric acid, IMPA - isopropyl methylphosphonic acid, PMPA - pinacolyl methyl-phosphonic acid, EMPA - ethyl methylphosphonic acid, and MPA - methylphosphonic acid. 

The fluorophosphonates GB and GD hydrolyze first through the loss of fluorine and second, more slowly, through the loss of the alkoxy group (Kingery and Allen 1995 MacNaughton and Brewer 1994). Under acidic conditions, the products of GB hydrolysis are isopropyl methylphosphonic acid and fluoride the former slowly hydrolyzes to methyl phosphonic acid with the loss of isopropanol (Fig. 5). According to Clark (1989), alkaline hydrolysis results in isopro-... 

C 1H15NO2S 3339-36-4) see. Tiemoniuin iodide (2-oxononyl)phosphonic acid dimethyl ester (C11H23O4P 57497-25-9) see Unoprostone isopropyl (S)-4-[[4-[(2-oxo-4-oxazolidinyl)methyl]phenyl]hydrazo-no]butanenitrile... 

Hoskin FCG. 1956. Some observations concerning the biochemical inertness of methyl phosphonic and isopropyl methylphosphonic acids. Can J Biochem Physiol 34 743-746. 

Phosphonates, methyl-, diaryl, reaction with cy-cloheptaamylose, 23 240,241 Phosphonic acid, methyl-, isopropyl p -... 

This method is compatible with many functional groups and shows considerable selectivity. Phosphonic acid esters may be cleaved in the presence of carboxylic acid esters, and phosphonate methyl esters are cleaved approximately 25 times faster than the isopropyl esters. For example, the phosphonate methyl ester of the hexapeptide analogue 78 was cleaved with TMSBr to give the aspartic peptidase inhibitor 79 in 64% yield (Scheme 28). 66 ... 

METHYL PHOSPHONIC DICHLORIDE see MOB399 METHYLPHOSPHONOFLUORIDIC ACID ISOPROPYL ESTER see IPXOOO METHYLPHOSPHONOFLUORIDIC ACID-1-METHYLETHYL ESTER see IPXOOO METHYLPHOSPHONOTHIOIC ACID-S-(2-(BIS(METHYLETHYL)AAaNO)ETHYL)o-ETHYL ESTER see EIGOOO... 

A number of acylphosphonic acids are of interest for their biological activity, or as intermediates in syntheses of potentially bioactive phosphonic acids [7, 34, 48 - 50]. In many cases, they are most conveniently prepared by hydrolysis of the corresponding esters. Due to the presence of the keto function, acid hydrolysis (heating in aqueous HCl) is generally not a practical method to achieve this. Silyldealkylation of methyl-, ethyl- or isopropyl phosphonates with BTMS, followed by very mild hydrolysis is normally compatible with acyl and other sensitive functionalities [7,34,48]. 

New developments in the synthesis of a-hydroxy phosphonic acids and their derivatives have concentrated on their asymmetric formation. The chiral phosphonic diamides (629) (in which R = isopropyl, 2,2-dimethylpropyl, or benzyl or a derivative thereof) in either racemic or optically active forms were converted into their anions and allowed to react with aldehydes to give the products (630) the diastereoisomeric composition of the latter could be ascertained by the use of P NMR spectroscopy, and after acidic hydrolysis and subsequent methylation (diazomethane) it was possible to isolate optically active forms of the dimethyl esters of (l-hydroxyalkyl)phos-phonic acids, the (/ ,R)-diamide giving rise to the (5)-acids as their esters. The best results were achieved when R = Bu CFl2, and enantiomeric excesses were generally above 85% . 

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. 1 HPLC-ESP MS reconstructed (total) ion chromatogram from a standard mixture of alkyl phosphonic acids at a concentration of 1 p-g/ml each 1) methylphosphonic acid (MPA) 2) ethylphosphonic acid (EPA) 3) methyl ethylphosphonic acid (MEPA) 4) ethyl methylphosphonic acid (EMPA) 5) ra-propylphosphonic acid (nPrPA) 6) ethyl ethylphosphonic acid (EEAP) 7) isopropyl methylphosphonic acid (iPrMPA) 8) n-propyl methylphosphonic acid (nPrMPA) 9) isopropyl ethylphosphonic acid (iPrEPA) 10) n-propyl ethylphosphonic acid (nPrEPA) 11) isohutyl methylphosphonic acid (iBuMPA) 12) cyclohexyl methylphosphonic acid (CHMPA) 13) pinacolyl methylphosphonic acid (PinMPA).

The reaction of 6-methylpyridine-3-carboxylic acid methyl ester with N,0-dimethylhydroxylamine and isopropyl-magnesium chloride in toluene gives the N-methoxyamide derivative (x), which is reduced with diisobutyl aluminium hydride (DIBAL) to afford 6-methylpyridine-3-carbaldehyde (xi). The reaction of the aldehyde (xi) with a phosphite provides the diphenyl phosphonate derivative, which is condensed with 4-(methylsulfonyl)benzaldehyde in the presence of potassium fe/f-butoxide in HF to yield the enimine (xii). Finally, this compound is hydrolyzed with HCI to yield the ketosulfone (ix). 

The simultaneous and selective protection of the two equatorial hydroxyl groups in methyl dihydroquinate [11L1, Scheme 3.111 j as the butane-2,3-diace-tal 111 2 was a key strategic feature in a synthesis of inhibitors of 3-dehydroqui-nate synthase.205 Later in the synthesis, deprotection of intermediate 111.4 required three steps (a) hydrolysis of the trimethylsilyl ether and the butane-2,3-diacetal with trifluoroacetic acid (b) cleavage of the isopropyl phosphonate with bromotrimethylsilane and (c) hydrolysis of the methyl ester with aqueous sodium hydroxide. Compound 111 1 has also been used in the synthesis of inhibitors 3-dehydroquinate dehydratase206 and influenza neuraminadase207-208 as well as shikimic add derivatives.209 210... 

Carbonylbisphosphonate esters react smoothly with NH2OCH3. For example, reaction of the isopropyl ester gave the corresponding stable O-methyl oxime in 60% yield. The free oximes, and the corresponding oxime derivatives of acid bis-phosphonates, have not yet been subjected to systematic study. However, very preliminary work indicates that the free oxime of the parent acid in aqueous solution is unstable to fragmentation with C-P bond cleavage, similar to that encountered with the troika acids. 

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