Diethyl (difluoromethyl)phosphonate

Base Information

• Chemical Name: Diethyl (difluoromethyl)phosphonate
• CAS No.: 1478-53-1
• Molecular Formula: C5H11 F2 O3 P
• Molecular Weight: 188.111
• Hs Code.: 29319090
• European Community (EC) Number: 673-917-2
• DSSTox Substance ID: DTXSID20163803
• Nikkaji Number: J879.040J
• Wikidata: Q83032790
• ChEMBL ID: CHEMBL5207763
• Mol file: 1478-53-1.mol

Synonyms:1478-53-1;Diethyl (difluoromethyl)phosphonate;Difluoromethylphosphonic acid diethyl ester;diethyl (difluoromethane)phosphonate;diethyl difluoromethanephosphonate;diethyl difluoromethylphosphonate;1-[difluoromethyl(ethoxy)phosphoryl]oxyethane;Phosphonic acid, (difluoromethyl)-, diethyl ester;C5H11F2O3P;DIFLUOROMETHYLPHOSPHONICACIDDIETHYLESTER;MFCD00192023;Phosphonic acid,P-(difluoromethyl)-, diethyl ester;Diethyl(difluoromethyl)phosphonate;SCHEMBL193239;CHEMBL5207763;DTXSID20163803;diethyl difluoromethane phosphonate;diethyl(difluoromethyl)-phosphonate;diethyl-(difluoromethyl)-phosphonate;C5-H11-F2-O3-P;AKOS005216219;AS-68783;Diethyl (difluoromethyl)phosphonate, 97%;DifluoroMethylphosphonic acidDiethyl ester;SY062739;1-(difluoromethyl-ethoxyphosphoryl)oxyethane;difluoromethyl phosphonic acid diethyl ester;Difluoromethyl-phosphonic acid diethyl ester;CS-0094054;FT-0649833;(Difluoromethyl)phosphonic acid, diethyl ester;(difluoromethyl) phosphonic acid, diethyl ester;C13418;EN300-100935;A808702;1-[bis(fluoranyl)methyl-ethoxy-phosphoryl]oxyethane;J-008420;Phosphonic acid, P-(difluoromethyl)-, diethyl ester

Chemical Property of Diethyl (difluoromethyl)phosphonate

Chemical Property:

• Vapor Pressure: 1.29mmHg at 25°C
• Refractive Index: n20/D 1.388(lit.)
• Boiling Point: 179.2°Cat760mmHg
• Flash Point: 62.2°C
• PSA: 45.34000
• Density: 1.181g/cm³
• LogP: 2.47510
• Storage Temp.: 2-8°C
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 1.2
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 5
• Exact Mass: 188.04138753
• Heavy Atom Count: 11
• Complexity: 141

Purity/Quality:

97% ^*data from raw suppliers

Diethyl Difluoromethanephosphonate ^*data from reagent suppliers

Safty Information:

• Hazard Codes: Xi
• Statements: 34
• Safety Statements: 26-36/37/39

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOP(=O)(C(F)F)OCC
• General Description: Diethyl difluoromethylphosphonate is a key precursor used in the synthesis of (diethylphosphinyl)difluoromethyllithium, a reagent employed for introducing difluoromethylene or difluoromethyl groups into organic compounds, enhancing their biological activity. DIFLUOROMETHYLPHOSPHONIC ACID DIETHYL ESTER reacts with lithium diisopropylamide to generate the lithium reagent, which is then applied to various electrophiles such as ketones, aldehydes, and halides, yielding products with difluorinated moieties. The process demonstrates variable efficiency depending on the electrophile, with high yields achieved for some (e.g., Me3SiCl, EtBr) but lower success for others (e.g., allyl bromide). Additionally, intermediate adducts can be further transformed into 1,1-difluoro olefins via the Wadsworth-Emmons reaction. However, the method has limitations, as certain functional groups (e.g., nitro, pyridine) may lead to undesired rearrangements or failed reactions.

Technology Process of Diethyl (difluoromethyl)phosphonate

There total 54 articles about Diethyl (difluoromethyl)phosphonate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 88.0%

Chlorodifluoromethane (75-45-6) + phosphonic acid diethyl ester (762-04-9) → Diethyl difluoromethylphosphonate (1478-53-1)

Guidance literature:

phosphonic acid diethyl ester; With sodium; In tetrahydrofuran; at 20 ℃; for 24h;

Chlorodifluoromethane; In tetrahydrofuran; for 15h;

DOI:10.1021/jo051511c

Reference yield: 86.0%

trimethyl(difluoromethyl)silane (65864-64-4) + diethyl chlorophosphate (814-49-3) → Diethyl difluoromethylphosphonate (1478-53-1)

Guidance literature:

With potassium 2-methylbutan-2-olate; In tetrahydrofuran; toluene; at 0 - 20 ℃; for 4h; chemoselective reaction; Inert atmosphere;

DOI:10.1039/d1ob00273b

Reference yield: 72.0%

4-methoxybenzenediazonium tetrafluoroborate (459-64-3) + diethyl difluoro(trimethylsilyl)methylphosphonate (80077-72-1) → Diethyl difluoromethylphosphonate (1478-53-1) + diethyl α,α-difluoro-4-methoxybenzylphosphonate

Guidance literature:

diethyl difluoro(trimethylsilyl)methylphosphonate; With copper(I) thiocyanate; cesium fluoride; In acetonitrile; at 0 - 40 ℃; for 2h; Glovebox; Sealed tube; Inert atmosphere;

4-methoxybenzenediazonium tetrafluoroborate; In acetonitrile; at 20 ℃; for 16h; Reagent/catalyst; Solvent; Catalytic behavior; Glovebox; Sealed tube; Inert atmosphere;

DOI:10.1002/chem.201703542

upstream raw materials:

Chlorodifluoromethane

sodium diethyl phosphite

phosgene

[(diethoxyphosphoryl)difluoromethyl]zinc bromide

Downstream raw materials:

diethyl (5-bromo-1,1-difluoropentyl)phosphonic acid

diethyl difluoro(trimethylsilyl)methylphosphonate

(1,1-Difluoro-2-phenoxythiocarbonyloxy-2-phenyl-ethyl)-phosphonic acid diethyl ester

(2-Cyclohexyl-1,1-difluoro-2-phenoxythiocarbonyloxy-ethyl)-phosphonic acid diethyl ester

Refernces

(DIETHYLPHOSPHINYL)DIFLUOROMETHYLLITHIUM. -PREPARATION AND SYNTHETIC APPLICATION-

10.1016/S0040-4039(00)87332-3

The research focuses on the preparation and synthetic application of (diethylphosphinyl)difluoromethyllithium, a reagent derived from the reaction of lithium diisopropylamide with diethyl difluoromethylphosphonate. The purpose of this study is to introduce difluoromethylene or difluoromethyl units into various electrophiles, which can lead to a remarkable enhancement of biological activity in organic compounds, as observed in the case of halogenated pesticides like decamethrin and NRDC-1821. The researchers successfully synthesized a range of compounds with difluoro-methylene or difluoromethyl groups from ketones and aldehydes, using this reagent. They found that the reaction yields varied depending on the electrophiles used, with some achieving high yields such as Me3SiCl (87%) and EtBr (82%), while others like CH2=CHCH2Br resulted in lower yields (23%). The study also explored the conversion of intermediate adducts into 1,1-difluoro olefins using the Wadsworth-Emmons reaction. The chemicals used in this process include diethyl difluoromethyl phosphonate, lithium diisopropylamide, and various electrophiles such as Me3SiCl, n-Bu3SnCl, (EtO)2P(O)Cl, and EtBr, among others. The conclusions drawn from the research indicate that while the procedure is generally applicable to various ketones and aldehydes, certain functional groups like nitro or pyridine rings did not yield the desired products and sometimes led to rearrangements.