Difluoro acetic acid

The use of trichloro-, trifluoro-, or difluoro-acetic acids in conjunction with phosphorus oxychloride similarly alfords tri(or di)halogenomethyl-1,3,4-thiadiazoles (130)—(132). However, the condensation of chloroacetyl chloride with thiosemicarbazide did not yield the expected heterocyclic product, but gave merely l,l-bis(chloroacetyl)thiosemicarbazide, (ClCHaCO)2NNHCSNH2. ... 

A group of Russian workers [22 to 27] reported on the fluorination of mixtures of solid amines, amides, or cyano compounds with KF or CaF2. The reactions were carried out in a stream of F2 diluted with N2 at about -10 to +10°C. NF3 was one of the main products and was accompanied by fluorinated fragments of the compounds treated. The N-containing compounds studied include aliphatic amine hydrochlorides [22, 23], the amides of trifluoro- and difluoro acetic acid [24], potassium cyanate [25], silver and potassium thiocyanate [26], and a acetonitrile boron trifluoride complex [27]. 

C4H6F2O2 difluoro-acetic acid ethyl ester 454-31-9... 

Direct fluorination of propionyl fluoride and acetic anhydride has failed to yield the corresponding fluorocarbon derivatives the former sub strate gave a complex mixture of fluorinated propionyl fluorides, and hy drolysis of the product from the latter yielded a mixture of monofluM o and difluoro-acetic acids. 

Diethyl Ar,Af-dimethylaminomethylenemalonate was reacted with 7,8-difluoro-3-methyl-l,4-benzoxazine in acetic acid at 80-90°C for 5 hr to give (l,4-benzoxazin-4-yl)methylenemalonate (272) in 74.8% yield [86JAP(K)246172, 86J AP( K)246188]. 

Ethyl 6-amino-4,5-difluoro-l-methyl-7-oxo-li/,7//-pyrido[3,2,l-i/]cinno-line-8-carboxylate (84, R = H) was prepared from the 6-benzylamino derivative 84 (R = CH2Ph) by catalytic debenzylation over Pd/C in a mixture of ethanol and acetic acid (92EUP470578,92MIP1). 

Difluoroacetic anhydride reacts similarly with alanine and this process affords 2-(difluoromethyl)-4-methyl-5(277)-oxazolone 7. Treatment of 7 with hydrogen bromide in acetic acid in the presence of ethanethiol yields 8 that was converted to 3,3-difluoroalanine 11 in several steps as shown in Scheme 7.3. ° This reaction opened the way to prepare p,(3-difluoro amino acids. 

Poly(arylene ether)s containing phenylimidazole units were initially prepared from the reaction of 2-phenyl-4,5-di(4-hydroxyphenyl)imidazole and various activated aromatic difluoro compounds according to Eq. (4) [20]. The dihydroxyimidazole was first prepared from the reaction of 4,4 -dimethoxyben-zil, benzaldehyde and ammonium acetate in refluxing acetic acid followed by... 

Reaction of AT-fluorobis(trifluoromethylsulfonyl)amine (Id) with alkenes gives various products, depending on the reaction conditions and the structure of the substrate. In solvents of higher nucleophilicity such as water, acetic acid, aqueous hydrochloric acid, and 70 % hydrogen fluoride/pyridine, a-fluorohydrins or their acetates, a-chloro-fl-fluoroalkanes or a,/ -difluoroal-kanes, e.g. 14. are obtained.146 Reaction of styrene and ( >l-phenylpropene with Id in dich-loromethane/acetic acid gives l-acetoxy-2-fluoro-l-phenylethane and -propane, in 92 and 99 % yield, respectively, the latter product in a ratio (erythrojthreo) 1 l.146... 

Pyrimidine-2,4(1//,3//)-dione (uracil) does not react with 7V-fluorobis(trifluoromethylsul-fonyl)amine (Id) at 22 C in acetic acid, probably due to its insolubility, but when heated at 45 CC for 12 hours it gives a difluorinated acetoxy derivative which could not be isolated.114 1,3-Dimethyluracil reacts with two equivalents of 1 d at 22 °C to give 6-acetoxy-5,5-difluoro-l, 3-dimethyl-5,6-dihydrouracil in 85% yield while with one equivalent of Id 5-fluoro-l, 3-dimethyl-uracil (mp 132-134°C) is also obtained.114... 

FLUORINE COMPOUNDS, ORGANIC - FLUORINATED ACETIC ACIDS] (Volll) Ethyl 3-(2,5-difluoro-4-bromophenyl)-3-oxopropanoate [123942-12-1]... 

The C-F bonds in l,l-difluoro-l,2-diphenylcthane (5) are resistant to several reducing agents the substrate is recovered unchanged after exposure to 2% sodium amalgam in ethanol or to zinc dust in refluxing ethanol and refluxing acetic acid. It is only partially converted into a mixture of 1,2-diphenylethane and ( )-l,2-diphenylethene with lithium aluminum hydride in refluxing dibutyl ether. On the other hand, catalytic reduction over palladium catalyst is completely successful.74... 

Acetic Acid Difluoro-nitro- EI0b2, 417 (CF2 N02 - COOH/ CF,0 NO -> COOH)... 

Acetic Acid Difluoro-[2-trifluoro-cthcnyioxy )-trifluoro-1-trifluoro mcthyl-cthvloxy]- ElOb2. 77 (CF3-SO -F -> COOH)... 

The following give abnormal results when treated with chlorosulphonic acid alone, preferably at 50 °C for 30-60 minutes fluorobenzene (4,4 -difluoro-diphenylsulphone, m.p. 98 °C) iodobenzene (4,4 -diiododiphenylsulphone, m.p. 202 °C) o-dichlorobenzene (3,4,3, 4 -tetrachlorodiphenylsulphone, m.p. 176 °C) and o-dibromobenzene (3,4,3, 4 -tetrabromodiphenylsulphone, m.p. 176— 177 °C). The resulting sulphones may be crystallised from glacial acetic acid, toluene or ethanol, and are satisfactory for identification of the original aryl halide. In some cases sulphones accompany the sulphonyl chloride they are readily separated from the final sulphonamide by their insolubility in cold 6 m sodium hydroxide solution the sulphonamides dissolve readily and are reprecipitated by 6 m hydrochloric acid. 

A mixture of 430 mg of the 16,21-diacetate of 6a,9a-difluoro-16a-hydroxy-prednisolone, 15 cc of methanol and 2.2 cc of a 4% aqueous solution of potassium hydroxide was stirred at 0°C in an atmosphere of nitrogen the material entered rapidly in solution and reprecipitated after 30 minutes. The mixture was then stirred for 1 hour more at 0°C and under an atmosphere of nitrogen, then neutralized with acetic acid and the methanol was distilled under reduced pressure. The residue was triturated with water, the solid was collected, washed with water, dried and recrystallized from ethyl acetate-methanol, thus giving 285 milligrams of the free 6a,9a-difluoro-16a-hydroxy-prednisolone, MP 258° to 260°C the analytical sample showed MP 266° to 268°C. 

In 135 ml THF was dissolved 3.03 g of a 3,5-dinitrobenzoyl derivative of (-)-3-acetoxymethyl-7,8-difluoro-2,3-dihydro-4H-[l,4]benzoxazine, and 135 ml of ethanol and 30 ml of 1.0 N potassium hydroxide were added to the solution. After 30 min 3 ml of acetic acid was added thereto for neutralization. The mixture was concentrated. The solid was subjected to column chromatography using 40 g of silica gel and eluted with chloroform/methanol to obtain 1.17 g of (-)-7,8-difluoro-2,3-dihydro-3-hydroxymethyl-4H-[l,4]benzoxazine [a]D22 = -14.1° (c = 1.80, CHCI3). 

In 12 ml of acetic acid was dissolved 1.20 g of the resulting compound, and 25 ml of concentrated hydrochloric acid was added, followed by refluxing at 120-130°C for 90 min. Upon allowing the reaction mixture to stand at room temperature, colorless crystals were precipitated, which were collected by filtration and washed successively with a small amount of water, ethanol and diethyl ether to obtain 0.96 g of (-)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]benzoxazine-6-carboxylic acid. 

To the ethyl l-cyclopropyl-6,7-difluoro-l,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylate (4.5 g) was added a mixed solution of acetic acid (30 ml), concentrated sulfuric acid (4 ml) and water (22 ml), and the mixture was refluxed for 1 h. After cooling, ice water (100 ml) was added and the resulting precipitate was collected by filtration, washed with water and then dried to give 1-cyclopropyl-6,7-difluoro-l,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid (4 g) as colorless powder, melting point 185°-186°C. 

On reaction with sodium iodide in glacial acetic acid, 1,2,4-trioxolanes undergo a reductive ring cleavage which will be discussed in Section 4.33.3.3.6. In the presence of potassium fluoride, 5,5-difluoro-l,2,4-trioxolan-3-one (136) isomerized at low temperatures to give bis(fluoroformyl) peroxide (137). Since the reaction is reversible (cf. Section 4.33.4.2.5), isomerization occurred with an equilibrium being established (72IC2531). 

Cyclopropanecarboxylic acid, 2,2-difluoro-, butyl ester and Acetic acid, difluoro... 

Acetic acid, difluoro(fluorosulfonyl)-, trimethylsilyl ester (9) (120801-75-4)... 

Abramov nucleophilic addition of various phosphorus acid esters to nucleoside aldehyde derivatives yielded the phosphonate-based iso-polar, non-iso-steric 5 -nucleotide analogues (28) containing a geminal hydroxy phosphonate moiety on the 5 -carbon of the pentofuranose ring. The enantiomerically pure D- and l- 2, 3, 5 -trideoxy-4 -[(ethoxyphosphoryl) difluoromethyl] thymidine analogues(29) have been synthesized from (i 5)-( )-2-methyl-5-(4-methyl-phenyl-sulfinyl)pent-2-ene and ethyl 2-(diethoxyphosphoryl)-2,2-difluoro-acetate in 45% overall yield over seven steps. ... 

Mineral acids such as hydrochloric acid undergo addition to cycloproparenes to give benzylic derivatives in almost quantitative yield. Weaker acids such as alcohols, thiols and amines undergo a similar addition in the presence of a catalytic amount of silverfl). The addition products of the simple cycloproparenes are usually of no preparative interest but the silver(I)-catalyzed electrophilic addition of methanol or acetic acid to 1 //-3,8-methanocyclopropa[l 0]an-nulene opens a simple access to 3-substituted l,6-methano[10]annulenes la,b and their 11,11-difluoro derivative Ic. ... 

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