1478-53-1

Basic information

• Product Name: DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER
• Synonyms: DIETHYL (DIFLUOROMETHANE)PHOSPHONATE;DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER;diethyl(difluoromethyl)phosphonate;DIETHYL (DIFLUOROMETHYL)PHOSPHONATE 96%;P-DifluoroMethylphosphonic Acid Diethyl Ester;1-[difluoromethyl(ethoxy)phosphoryl]oxyethane
• CAS NO: 1478-53-1
• Molecular Formula: C₅H₁₁F₂O₃P
• Molecular Weight: 188.11
• Product Categories: Inhibitors;Intermediates;Phosphorylating and Phosphitylating Agents
• Mol File: 1478-53-1.mol
• Article Data: 29

Chemical Properties

• Boiling Point: 96°C 15mm
• Flash Point: 113 °C
• Appearance: /
• Density: 1.193
• Vapor Pressure: 1.29mmHg at 25°C
• Refractive Index: n20/D 1.388(lit.)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER(1478-53-1)
• EPA Substance Registry System: DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER(1478-53-1)

Safety Data

• Hazard Codes: Xi
• Statements: 34
• Safety Statements: 26-36/37/39
• RIDADR: 3265
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 1478-53-1(Hazardous Substances Data)

Usage

Description

DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER is a colorless liquid that serves as an inhibitor of bacterial phosphotriesterases and is also used as an intermediate for the synthesis of 5'-diphosphate/5'-triphosphate mimics for transcriptase and glycerol kinase inhibition.

Uses

Used in Pharmaceutical Industry:
DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER is used as an inhibitor for bacterial phosphotriesterases, which are enzymes involved in the detoxification of organophosphates. This application is crucial in the development of new antibiotics and antimicrobial agents to combat drug-resistant bacteria.
Used in Biochemical Research:
As an intermediate for the synthesis of 5'-diphosphate/5'-triphosphate mimics, DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER plays a significant role in the study of transcriptase and glycerol kinase inhibition. These mimics are essential for understanding the mechanisms of these enzymes and can lead to the development of novel therapeutic agents for various diseases.
Used in Chemical Synthesis:
DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER is also utilized as a versatile intermediate in the synthesis of various organic compounds, particularly those involving phosphonic acid derivatives. Its unique chemical properties make it a valuable building block for the creation of new molecules with potential applications in various industries, including pharmaceuticals, agrochemicals, and materials science.

Synthesis Reference(s)

Tetrahedron Letters, 23, p. 2323, 1982 DOI: 10.1016/S0040-4039(00)87332-3

InChI:InChI=1/C5H11F2O3P/c1-3-9-11(8,5(6)7)10-4-2/h5H,3-4H2,1-2H3

Upstream product

• 82845-20-3 [(diethoxyphosphoryl)difluoromethyl]zinc bromide 
• 2941-64-2 Ethyl chlorothioformate 
• 65094-22-6 diethyl (bromodifluoromethyl)phosphonate 
• 140-88-5 ethyl acrylate 
• 65864-64-4 trimethyl(difluoromethyl)silane 
• 814-49-3 diethyl chlorophosphate 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 762-04-9 phosphonic acid diethyl ester 
• 5029-67-4 2-iodopyridine 
• 80077-72-1 diethyl difluoro(trimethylsilyl)methylphosphonate 
• 459-64-3 4-methoxybenzenediazonium tetrafluoroborate 
• 166330-03-6 pinacol (bromomethyl)boronate 
• 58310-30-8 bromodifluoromethyl[tris(dimethylamino)]phosphonium bromide 
• 122-52-1 triethyl phosphite 

Downstream Products

• 127727-15-5 diethyl (5-bromo-1,1-difluoropentyl)phosphonic acid 
• 130434-89-8 5-iodo-1,1-difluoro-1-(diethylphosphono)pentane 
• 151076-11-8 3-O-Benzyl-5,6-dideoxy-6-(diethoxyphosphinyl)-6,6-difluoro-1,2-O-isopropylidene-β-D-ribo-hexofuranose 
• 151076-02-7 benzyl 6-deoxy-6-[(diethylphosphono)difluoromethyl]-2,3,4-tri-O-benzyl-β-D-glucopyranoside 
• 64-17-5 ethanol 
• 110624-94-7 Difluoromethyl-phosphonic acid; compound with cyclohexylamine 
• 141642-57-1 [1,1-Difluoro-2-phenoxythiocarbonyloxy-2-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)-ethyl]-phosphonic acid diethyl ester 
• 13464-19-2 phenyl chlorothioformate 
• 141642-58-2 [2-((R)-2,2-Dimethyl-[1,3]dioxolan-4-yl)-1,1-difluoro-2-phenoxythiocarbonyloxy-ethyl]-phosphonic acid diethyl ester 
• 192211-54-4 ((2R,3R,4R,5R)-2-Benzylamino-3,4,6-tris-benzyloxy-1,1-difluoro-5-hydroxy-hexyl)-phosphonic acid diethyl ester 
• 192211-57-7 ((2S,3R,4R,5R)-2-Benzylamino-3,4,6-tris-benzyloxy-1,1-difluoro-5-hydroxy-hexyl)-phosphonic acid diethyl ester 
• 192211-56-6 ((2R,3R,4R,5S)-2-Benzylamino-3,4,6-tris-benzyloxy-1,1-difluoro-5-hydroxy-hexyl)-phosphonic acid diethyl ester 
• 192211-59-9 ((2S,3R,4R,5S)-2-Benzylamino-3,4,6-tris-benzyloxy-1,1-difluoro-5-hydroxy-hexyl)-phosphonic acid diethyl ester 
• 192211-55-5 ((2R,3S,4R,5R)-2-Benzylamino-3,4,6-tris-benzyloxy-1,1-difluoro-5-hydroxy-hexyl)-phosphonic acid diethyl ester 

Relevant articles and documents

Preparation and synthetic application of diethyl 2-oxo-1,1-difluorophosphonates

Reaction of diethyl(bromodifluoromethyl)phosphonate (EtO)2P(O)CF2Br 1 with activated zinc gave [(diethoxyphosphonyl)difluoromethyl]zinc bromide (EtO)2P(O)CF2ZnBr 2, which was acylated with various acylating agents to afford diethyl 2-oxo-1,1-difluorophosphonates (EtO)2P(O)CF2C(O)R 4 in good yields. Treatment of phosphonates 4 such as diethyl 2-oxo-1,1-difluoropropylphosphonate (EtO)2P(O)CF2C(O)CH3 4a, ethyl difluoro(diethoxyphosphonyl)pyruvate (EtO)2P(O)CF2C(O)CO2Et 4e and N,N-diethyldifluoro(diethoxyphosphonyl)acetamide (EtO)2P(O)CF2C(O)NEt2 4h with Grignard reagents R'MgX provided 1,1-difluoroolefins R′(CH3)C=CF2, R′(CO2Et)C=CF2 and R′(NEt2) C=CF2, respectively.

Automated lineshape analysis of complex NMR spectra for a novel synthetic tetrafluorobisphosphonate, a potential ligand for phosphoglycerate kinase

Tetraalkyl 1,1,3,3-tetrafluoro-2,2-dihydroxypropane-1,3-bisphosphonates were prepared. The complex 31P{1H}- and 19F-NMR spectra were analyzed as [[A]2X]2 and related systems. Modern methods of automated spectral analysis using DAISY under WIN-NMR were applied.

Syntheses of ω-hydroxy-α,α-difluoromethylphosphonates by oxacycle ring-opening reactions

(Chemical Equation Presented) Oxacycle ring-opening reactions from a non-HCFC-based source of phosphonodifluoromethyl carbanion 1 are reported. This straightforward strategy opens access to a variety of primary and secondary ω-hydroxy-α,α-difluoromethylphosphonates via one step. The syntheses of a glycerol monophosphate analogue and precursors to nucleoside phosphorylase inhibitors are described using this method.

Copper-promoted cross-coupling reactions for the synthesis of aryl(difluoromethyl)phosphonates using trimethylsilyl(difluoromethyl)phosphonate

A convenient and effective route for the synthesis of aryl(difluoromethyl)phosphonates has been developed based on cross-coupling reactions. Upon treatment with a stoichiometric amount (or a catalytic amount in some cases) of CuI and CsF, aryl iodides reacted smoothly with (silyldifluoromethyl)phosphonates to give the corresponding aryl(difluoromethyl)phosphonates in good yields.

Direct and straightforward transfer of C1 functionalized synthons to phosphorous electrophiles for accessinggem-P-containing methanes

The direct transfer of different α-substituted methyllithium reagents to chlorinated phosphorous electrophiles of diverse oxidation state (phosphates, phosphine oxides and phosphines) is proposed as an effective strategy to synthesize geminal P-containing

Copper-Mediated Introduction of the CF2PO(OEt)2 Motif: Scope and Limitations

Herein, a general procedure to access CF2PO(OEt)2-containing molecules is reported. The reagent CuCF2PO(OEt)2 is accessible by a simple protocol and a broad range of substrates can be functionalised. The procedure allows the conversion of aryl diazonium salts, as well as aryl, heteroaryl, vinyl and alkynyl iodonium salts, into the corresponding fluorinated molecules at room temperature. Mechanistic studies were performed to gain a better understanding of the reaction pathway. Under similar conditions, vinyl and aryl iodides, allyl halides, and benzyl bromides were also functionalised, and the scope and limitations of the reaction were studied. Finally, the procedure was extended to disulfides to offer new access to SCF2PO(OEt)2-containing molecules.