4408-78-0

Basic information

• Product Name: PHOSPHONOACETIC ACID
• Synonyms: PHOSPHONOETHANOIC ACID;PHOSPHONOACETIC ACID;AURORA KA-1453;Carboxymethanephosphonic acid;carboxymethanephosphonicacid;Fosfonet;Fosfonoacetic acid;Phosphonacetic acid
• CAS NO: 4408-78-0
• Molecular Formula: C₂H₅O₅P
• Molecular Weight: 140.03
• EINECS: 224-558-1
• Product Categories: Phosphonic/Phosphinic AcidsEnzyme Inhibitors by Enzyme;Proline dipeptidase;Organic Building Blocks;P to;Phosphorus Compounds
• Mol File: 4408-78-0.mol

Chemical Properties

• Melting Point: 143-146 °C(lit.)
• Boiling Point: 490.2 °C at 760 mmHg
• Flash Point: 250.2 °C
• Appearance: White powder
• Density: 1.858 g/cm³
• Vapor Pressure: 6E-11mmHg at 25°C
• Refractive Index: 1.5180 (estimate)
• Storage Temp.: 2-8°C
• Solubility: water: soluble100mg/mL, clear to very slightly hazy, colorless
• PKA: 1.74±0.10(Predicted)
• Water Solubility: Soluble in water.
• Sensitive: Hygroscopic
• BRN: 1764355
• CAS DataBase Reference: PHOSPHONOACETIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: PHOSPHONOACETIC ACID(4408-78-0)
• EPA Substance Registry System: PHOSPHONOACETIC ACID(4408-78-0)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 26-36/37/39
• RIDADR: UN3261
• WGK Germany: 3
• RTECS: AJ3278000
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 4408-78-0(Hazardous Substances Data)

Usage

Uses

1. Used in Antiviral Applications:
PHOSPHONOACETIC ACID is used as an antiviral agent, particularly for its ability to inhibit deoxyribo nucleic acid polymerase, which is essential for viral replication. This property makes it effective against a range of viruses and is utilized in the development of antiviral medications.
2. Used in Pharmaceutical Synthesis:
PHOSPHONOACETIC ACID is employed in the preparation of 1-(dimethylamino)-2,2-bis[(dimethylimmonio)-methyl]ethene diperchlorate by reacting with phosphorus oxychloride. PHOSPHONOACETIC ACID has potential applications in the pharmaceutical industry for the development of new drugs.
3. Used in Viral Research:
PHOSPHONOACETIC ACID has been used as an inhibitor of viral DNA replication to study the localization of infected cell protein 0 (bICP0) in infected low passage bovine cells. This application aids in understanding the mechanisms of viral infection and the development of targeted antiviral therapies.
4. Used in Microbial Growth:
PHOSPHONOACETIC ACID serves as a phosphorus source for microbial growth in a phosphate-independent manner. This application is particularly useful in the field of microbiology and biotechnology, where it can support the growth of specific microorganisms for various purposes, such as the production of biofuels, enzymes, or other valuable compounds.

InChI:InChI=1/C2H5O5P/c3-2(4)1-8(5,6)7/h1H2,(H,3,4)(H2,5,6,7)/p-3

Upstream product

• 2537-48-6 diethyl 1-cyanomethylphosphonate 
• 72946-10-2 diisopropyl (methoxycarbonylmethyl)phosphonate 
• 867-13-0 diethoxyphosphoryl-acetic acid ethyl ester 
• 78939-53-4 p-nitrophenyl phosphonoacetate 
• 1067-74-9 Methyl diethylphosphonoacetate 
• 5927-18-4 trimethyl phosphonoacetate 
• 67-56-1 methanol 
• 65868-40-8 ethyl P,P-bis(trimethylsilyl) phosphonoacetate 
• 64954-31-0 C₁₂H₂₉O₅PSi₂ 
• 16051-76-6 phosphonoacetalhdehyde 
• 53311-88-9 diisopropyl ester of isopropoxycarbonylmethylphosphonic acid 
• 35752-46-6 phosphonoacetic acid ethyl ester 

Downstream Products

• 35752-46-6 phosphonoacetic acid ethyl ester 
• 34164-06-2 dichlorophosphoryl-acetyl chloride 
• 5927-18-4 trimethyl phosphonoacetate 
• 62591-72-4 Propylphosphonoacetat 
• 2009-81-6 2-dimethylaminomethylene-1,3-bis(dimethylimonio)propane diperchlorate 
• 40203-73-4 Cyclopentylideneacetic acid methyl ester 
• 40962-37-6 phosphonoacetic acid trimethyl ester 

Relevant articles and documents

Complexation Properties of Phosphonocarboxylic Acids in Aqueous Solutions

The concentration formation constants of phosphonoacetic acid (PAA) complexes with the Ca(2+) and Mg(2+) ions were determined in aqueous solution at 25 deg C by potentiometric and coulometric titrations at different ionic strengths and were extrapolated to I = 0 in order to obtain thermodynamic values of the formation constants.Complexes were formed by the completely deprotonated Kf(ML) and monoprotonated Kf(MHL) forms of the PAA anion.The respective values for the complexes are: log Kf(CaL) = 4.68 +/- 0.03, log Kf(CaHL) = 2.61 +/- 0.08; log Kf(MgL) = 5.58 +/- 0.09, log Kf(MgHL) = 3.0 +/- 0.3.The enthalpy and entropy of complexation for the deprotonated Ca(2+) and Mg(2+) PAA species, determined from the temperature dependence of the log Kf(ML), are: ΔHo(Ca) = 0.6 +/- 0.2 kcal-mol-1, ΔSo(Ca) = 21.4 +/- 0.6 cal-mol-1-K-1, ΔHo(Mg) = 3.0 +/- 0.7 kcal-mol-1, and ΔSo(Mg) = 35 +/- 2 cal-mol-1-K-1.It is seen therefore, that the complexes are entropy stabilized but enthalpy destabilized.Formation constants were also determined for Ca(2+) and Mg(2+) complexes with PAA analogs, phosphonoformic and 3-phosphonopropionic acids and the complexation of PAA was also studied at a single ionic strength, with Na(1+), Ag(1+), Tl(1+), Sr(2+), Ba(2+), Cd(2+), Cu(2+), and Pb(2+) ions.

Biosynthesis of the Fungal Organophosphonate Fosfonochlorin Involves an Iron(II) and 2-(Oxo)glutarate Dependent Oxacyclase

The fungal metabolite Fosfonochlorin features a chloroacetyl moiety that is unusual within known phosphonate natural product biochemistry. Putative biosynthetic genes encoding Fosfonochlorin in Fusarium and Talaromyces spp. were investigated through reactions of encoded enzymes with synthetic substrates and isotope labelling studies. We show that the early biosynthetic steps for Fosfonochlorin involve the reduction of phosphonoacetaldehyde to form 2-hydroxyethylphosphonic acid, followed by oxidative intramolecular cyclization of the resulting alcohol to form (S)-epoxyethylphosphonic acid. The latter reaction is catalyzed by FfnD, a rare example of a non-heme iron/2-(oxo)glutarate dependent oxacyclase. In contrast, FfnD behaves as a more typical oxygenase with ethylphosphonic acid, producing (S)-1-hydroxyethylphosphonic acid. FfnD thus represents a new example of a ferryl generating enzyme that can suppress the typical oxygen rebound reaction that follows abstraction of a substrate hydrogen by a ferryl oxygen, thereby directing the substrate radical towards a fate other than hydroxylation.

The mckenna reaction – avoiding side reactions in phosphonate deprotection

The McKenna reaction is a well-known and popular method for the efficient and mild synthesis of organophosphorus acids. Bromotrimethylsilane (BTMS) is the main reagent in this reaction, which transforms dialkyl phosphonate esters into bis(trimethylsilyl)esters, which are then easily converted into the target acids. However, the versatile character of the McKenna reaction is not always used to its full extent, due to formation of side products. Herein, demonstrated by using model examples we have not only analyzed the typical side processes accompanying the McKenna reaction, but also uncovered new ones. Further, we discovered that some commonly recommended precautions did not always circumvent the side reactions. The proposed results and recommendations may facilitate the synthesis of phosphonic acids.

Composition on the basis of phosphonoacetic acid. Synthesis and antiviral activity

A manufacturable technology for the production of an antiviral composition containing phosphonoacetic acid, involing PH-alkylation of dimethyl phosphite with methyl chloroacetate under phase-transfer conditions and subsequent in situ hydrolysis of the intermediate product, was developed. The composition showed expressed antiviral effect against herpesviral infections caused by herpes simplex virus 1 and 2 and cytomegalovirus. The composition in the effective concentration range was found to exhibit no cytotoxic effect on VERO green monkey kidney and M-19 human diploid cell cultures. The resulting data suggest potential uses of the composition as an antiviral agent in practical medicine and as an antiviral additive to synthetic detergents for sanitation in health care and food production facilities.

Applications of mesoporous titanium phosphonate functionalized with carboxylic groups

Mesoporous titanium phosphonate functionalized with -COOH was synthesized by a simple co-condensation process with the use of 2-phosphonoacetic acid and titanium tetrachloride under acid conditions. The obtained mesoporous materials show high surface area and large pore volume, which were supported by XRD, TEM, SEM and N2 adsorption analysis. The integrity of the organophosphonate groups were further characterized by FTIR and NMR. Palladium nanoparticles were successfully supported onto the materials combined with a metal adsorption-reduction procedure, showing high activity for the Suzuki reaction. Furthermore, the obtained catalyst can be recovered and reused without significant decrease in catalytic activity. This journal is

Intramolecular monodealkylation during the attempted synthesis of diethylphosphonoacetohydroxamic acid

The reaction of diethyl methyl phosphonoacetate (1) with hydroxylamine in NaOH solution resulted in the loss of one of the phosphorus ethyl groups, and yielded monoethylphosphonoaceto-hydroxamic acid (2) as the major product (79%) and diethylphosphonoacetic acid (3) as the minor product (21%). A series of control experiments were carried out to elucidate the sequence of the reactions leading to 2. When the reaction of 1 with NH2OH was carried out in NaHCO3 solution, a transient product 4 was also observed, which slowly transformed to 2. Compound 4 was assigned the structure diethylphos-phonoacetohydroxamic acid. There was no dealkylation observed at the phosphorus when 1 was reacted with methoxylamine or when O-methyl diethylphosphonoacetohydroxamate (7) was placed in alkaline solution. The dealkylation at phosphorus was interpreted in terms of intramolecular nucleophilic catalysis by the hydroxamic OH group attacking the phosphorus in 4, involving cyclic 1, 2,5-oxazaphospholidine intermediates.

Phospholipid derivatives of phosphono-carboxylic acids, the production of said derivatives and the use of said derivatives as antiviral medicaments

PCT No. PCT/EP96/05647 Sec. 371 Date Aug. 27, 1998 Sec. 102(e) Date Aug. 27, 1998 PCT Filed Dec. 16, 1996 PCT Pub. No. WO97/22613 PCT Pub. Date Jun. 26, 1997The present invention concerns new lipid derivatives of phosphonocarboxylic acids of the general formula I, in which the meaning of the symbols is elucidated in the description, tautomers thereof and their physiologically tolerated esters and salts of inorganic or organic bases as well as processes for the production thereof and pharmaceutical agents containing these compounds.

ORGANOPHOSPHORUS COMPOUNDS AS ANTIVIRAL AGENTS

The 5'-triphosphates of 2'-5' linked oligoadenylic acids are formed in cells which have been exposed to interferon and may be involved in the antiviral activity of the latter.The lead(II) ion-catalysed oligomerisation of adenosin 5'-phosphorimidazolidate is a convenient route for the preparation of the 5'-phosphates of 2'-5' linked oligoadenylic acids.The latter can readily be converted to the triphosphates or coupled to the 5'-phosphate of nicotinamide nucleoside to give naturally occurring pyrophosphates which may act as reservoirs for the oligoadenylic acids in cells.Pyrophosphate analoques, eg. phophonoacetic and phosphonoformic acids or carbon-substituted methylenebisphosphonic acids are antiviral agents of potential commercial interest as they inhibit the replication of a number of viruses including herpes and influenza.These pyrophosphate analogues do not appear to inhibit virus replication by being incorporated into nucleoside triphosphates which block nucleic acid synthesis.Rather analogues appear to act by forming stable complexes with an essential metal ion (probably zinc) at the active sites of nucleic acid polymerases of viruses.

Effect of Phosphono Substituents on Acyl Transfer Reactions

The rate of release of p-nitrophenoxide from esters of phosphono-substituted carboxylic acids was examined as a function of pH(D), temperature, divalent metal ion (Mg2+ and Ca2+) concentration, and acyl acceptor (-OH and the thiolate of N-acetylcysteine).The hydrolysis of p-nitrophenyl 3-phosphonopropionate involves intramolecular nucleophilic catalysis by the dianionic phosphono substituent (pKa2(*) = 7.5) and is characterized by a first-order rate constant of 94 min-1 at 37 deg C.A comparison of the rate constant of the unimolecular reaction with that of the corresponding bimolecular reaction (corrected for the inductive effect of the acyl substituent and for the phosphonate basicity) yields a rate constant ratio of kuni/kbi = 7(+/-6)*103 M.The magnitude of this rate enhancement is similar to those of analogous intramolecular reactions (e.g., hydrolysis of mono-p-nitrophenyl succinate or of p-nitrophenyl 4-(N,N-dimethylamino)butyrate but, unlike these reactions, the rate acceleration resulting from intramolecular nucleophilic catalysis by the dianionic phosphono group is enthalpic in origin (Δ(*) ca. 8 kcal/mol).The entropy of activation for the intramolecular reaction is less favorable than that for the bimolecular reaction (Δ(*) ca. 9 eu).The alkaline hydrolysis and the thiolysis rates of p-nitrophenyl phosphonoacetate are accelerated over 100-fold by the association of Mg2+ or Ca2+ with the ester.This rate acceleration is attributed to the formation of a six-membered bidentate coordination complex between the divalent cation and the incipient tetrahedral intermediate.The metal-promoted acyl transfer reactions of p-nitrophenyl phosphonoacetate provide a convenient system for the quantitative assessment of the role of metal ions in the catalysis of aqueous reactions.