1478-53-1

Usage

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

• 75-45-6 Chlorodifluoromethane 
• 2303-76-6 sodium diethyl phosphite 
• 75-01-4 chloroethylene 
• 65094-22-6 diethyl (bromodifluoromethyl)phosphonate 
• 1660-94-2 Tetraethyl methylenediphosphonate 
• 78715-58-9 Tetraethyl difluoromethylenediphosphonate 
• 82845-20-3 [(diethoxyphosphoryl)difluoromethyl]zinc bromide 
• 624-65-7 2-propynyl chloride 
• 78-94-4 methyl vinyl ketone 
• 682-30-4 Diethyl vinylphosphonate 
• 762-04-9 phosphonic acid diethyl ester 
• 80084-30-6 (diethylphosphono)difluoromethyl cadmium bromide 
• 870-63-3 prenyl bromide 
• 75-56-9 methyloxirane 

Downstream Products

• 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 
• 141642-56-0 (1,1-Difluoro-2-phenoxythiocarbonyloxy-2-phenyl-ethyl)-phosphonic acid diethyl ester 
• 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 
• 141642-58-2 [2-((R)-2,2-Dimethyl-[1,3]dioxolan-4-yl)-1,1-difluoro-2-phenoxythiocarbonyloxy-ethyl]-phosphonic acid diethyl ester 
• 78715-58-9 Tetraethyl difluoromethylenediphosphonate 
• 97480-37-0 Diethyl phosphoryl-2,2-difluoroacetic acid 
• 226544-67-8 Diethyl difluoromethylphosphonate 
• 164580-01-2 (3-benzyloxy-1,1-difluoro-2-hydroxy-propyl)-phosphonic acid diethyl ester 
• 528523-58-2 tert-butyl (4S,5S)-4-[(1R)-2-(diethoxyphosphoryl)-2,2-difluoro-1-hydroxyethyl]-2,2-dimethyl-5-phenyl-1,3-oxazolidine-3-carboxylate 
• 528523-50-4 (4S,5R)-4-[(R)-2-(Diethoxy-phosphoryl)-2,2-difluoro-1-hydroxy-ethyl]-2,2-dimethyl-5-phenyl-oxazolidine-3-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

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.

Nucleophilic fluoroalkylation of (bromomethyl)pinacolborane using silicon reagents

A method for the synthesis of pinacol boronic esters bearing a fluorinated group at the a-carbon atom (RfCH2Bpin) from corresponding bromomethyl borane (BrCH2Bpin) and fluorinated silanes (RfSiMe3) is described. The fluoroalkylation reaction involves formation of borate anions followed by intramolecular nucleophilic substitution of bromine.

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.

Synthesis of Novel Fluorinated Bisphosphonates and Bisphosphonic Acids

The synthesis of novel fluorinated bisphosphonates with two, three, four, and six difluoromethylene groups (1a, 1b, 8, 12, and 15) (44-78percent) by different approaches is described.The bisphosphonates were converted to the corresponding trimethylsilyl esters which on treatment with deionized water afforded the respective bisphosphonic acids (6, 10, and 14) 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

Siladifluoromethylation and Deoxo-trifluoromethylation of PV-H Compounds with TMSCF3: Route to PV-CF2- Transfer Reagents and P-CF3 Compounds

A method for siladifluoromethylation of dialkyl phosphonates and secondary phosphine oxides with TMSCF3 to produce nucleophilic PV-CF2- transfer reagents is disclosed, with multigram scale reactions included. Condition-dependent divergent reactivity under the established conditions is demonstrated by the formation of trifluoromethylphosphines. Both one-pot transformations are operationally simple and employ inexpensive materials. Mechanistic investigations suggest the divergent reactivity originates from a common intermediate, with Li+ concentration directing the chemoselectivity.

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.

Synthetic and mechanistic aspects of halo-F-methylphosphonates

The synthesis of a variety of new halo-F-methylphosphonates has been achieved by a Michaelis-Arbuzov type reaction between a halo-F-methane and a trialkyl phosphite. This synthesis has proved to be of wide scope and utility for the high yield preparation of a number of heretofore unknown compounds. The 1H, 19F, 13C and 31P NMR spectroscopic properties are reported in detail. The mechanism for the formation of bromodifluoromethylphosphonates has been shown to proceed through the intermediacy of difluorocarbene:CF2. The phosphonate products have been shown to react with a wide variety of reagents. Fluoride and alkoxide ions react by attack at phosphorus with cleavage of the carbon-phosphorus bond and formation of [:CF2] from the bromodifluoromethylphosphonates and the CFBr2- anion from the dibromofluoromethylphosphonates. Iodide ion and tertiary phosphines react by attack at the ester carbon to give stable phosphonate salts. Hydrolysis of the phosphonate esters with 50% aqueous HCl gives the expected phosphonic acids. Trimethylsilyl bromide attacks phosphoryl oxygen to afford the bis(trimethylsilyl) esters.