17843-01-5Relevant academic research and scientific papers
Synthesis of α-fluorinated phosphonoacetate derivatives using electrophilic fluorine reagents: Perchloryl fluoride versus 1-chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor)
Marma, Mong S.,Khawli, Leslie A.,Harutunian, Vahak,Kashemirov, Boris A.,McKenna, Charles E.
, p. 1467 - 1475 (2005)
Triethyl fluorophosphonoacetate and triethyl difluorophosphonoacetate are directly synthesized from triethyl phosphonoacetate by treatment with NaH and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor). Contrary to a recent report [C.J. Hamilton, S.M. Roberts, J. Chem. Soc., Perkin Trans. 1 (1999) 1051-1056], the reaction proceeded in THF without the need for DMF as a co-solvent. This method is more selective and provides greater convenience and safety than fluorination of the same substrate by treatment with t-BuOK and perchloryl fluoride (FClO3) in toluene while offering advantages over a number of previously described methods employing alternative electrophilic fluorinating reagents or other approaches. Either the monofluoro or the difluoro product can be obtained predominantly by adjusting the molar ratio of base and Selectfluor. Triethyl 2-fluoro-2-phosphonopropionate (ethyl 2-(diethoxyphosphinyl)-2-fluoropropanoate) is also more conveniently made from triethyl 2-phosphonopropanoate using NaH/Selectfluor in THF than with FClO3/t-BuOK in toluene. Detailed procedures are given for obtaining the corresponding triacids in quantitative yield from the fluorinated triesters by P,P-silyldealkylation with bromotrimethylsilane followed by one-pot double hydrolysis with H2O, and isolation as stable dicyclohexylammonium (DCHA) or pyridinium (Py) salts. Substitution of EtOH for H2O in the latter procedure provides the CO-ester phosphonic diacids, isolated as DCHA salts, in one step. 1H, 13C, 31P and 19F NMR data are given for the compounds prepared.
A Safe Facile Synthesis of Difluorophosphonoacetic Acid
Burton, Donald J.,Sprague, Lee G.,Pietrzyk, Donald J.,Edelmuth, Steven H.
, p. 3437 - 3438 (1984)
Copper(I) halide catalyzed acylation of zinc bromide with ethyl chloroformate provides a safe, easily scaled up preparation of ethyl difluoro(diethoxyphosphinyl)acetate from readily available precursors.Silylation of this ester, followed by hydrolysis, gives difluorophosphonoacetic acid.
Elemental fluorine. Part 9 : Catalysis of the direct fluorination of 2-substituted carbonyl compounds
Chambers, Richard D.,Hutchinson, John
, p. 45 - 52 (2007/10/03)
Catalysis of the reaction between fluorine and a range of 2-substituted carbonyl compounds has been investigated. Most notably, the preparation of diethyl-2-fluoromalonate has been achieved in high yield by fluorination of diethylmalonate in the presence of hydrated copper nitrate. Reactions between fluorine and carbanions derived from 2-substituted carbonyl compounds, including phosphonates, sulphones and nitriles, are also discussed.
Synthesis of 3′-arylsulfonyl-4′-[(diethoxyphosphoryl)difluoromethyl]thymidine analogs
Arnone, Alberto,Bravo, Pierfrancesco,Frigerio, Massimo,Viani, Fiorenza,Zappala, Carmela
, p. 1511 - 1518 (2007/10/03)
D- and L-Diethoxyphosphoryldifluoromethyl nucleoside analogs 8, bearing a sulfonylic moiety at C-3′ were synthesized following the building block approach to chiral fluorinated molecules. The condensation of ethyl 2-(diethoxyphosphoryl)2,2-difluoroacetate (2) and 4-(4-methylphenylsulfinyl)but-l-ene (3) followed by reduction of the thus formed ketones 4 to alcohols 5 and oxidative cyclization to the furanose derivatives 6 were the key steps of the synthetic sequence.
Preparation and synthetic application of diethyl 2-oxo-1,1-difluorophosphonates
Tsai, Hou-Jen
, p. 247 - 259 (2007/10/03)
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.
Preparation of Difluorophosphonoacetic Acid and Its Derivatives
Burton, Donald J.,Sprague, Lee G.
, p. 1523 - 1527 (2007/10/02)
The preparation of ethyl difluoro(diethoxyphosphinyl)acetate (1) has been effected by the acylation of zinc bromide with ethyl chloroformate in the presence of a catalytic amount of cuprous bromide.Similarly prepared were ethyl difluoro(diethoxyphosphinyl)pyruvate (2) and N,N-diethyldifluoro(diethoxyphosphinyl)acetamide (3).Bromotrimethylsilane selectively reacted with 1 to yield ethyl difluoroacetate (9).The remaining ethyl carboxylic ester of 9 reacted with iodotrimethylsilane to produce trimethylsilyl difluoroacetate (10), which was subsequently hydrolyzed to yield difluorophosphonoacetic acid (8).The phosphonate 9 was gently chlorinated to yield ethyl difluoro(dichlorophosphinyl)acetate (11).
Studies on Selected Transformations of Some Fluoromethanephosphonate Esters
Blackburn, G. Michael,Brown, David,Martin, Stephen J.,Parratt, Martin J.
, p. 181 - 186 (2007/10/02)
The thermal stability of α-fluoromethanephosphonate carbanions decreases in the series CHF>CF2>CFCl.Acylation products of the difluoromethanephosphonate carbanion show high electrophilic reactivity which results in the inmediate formation of secondary products.This behaviour is not observed for the monofluoromethanephosphonate carbanion.Attemps to acylate or phosphorylate the chlorofluoromethanephosphonate carbanion unexpectedly provide esters of fluoromethylenebisphosphonic acid as products.Some physical characteristics of fluoromethanephosphonic acids are described.
