Furans trifluoromethyl

Furan-2-carbaldehyde, 5-trifluoromethyl- H NMR, 4, 558 (68JHC95) Furan-2-carbaldehyde oxime, 5-nitro-X-ray, 4, 537 (72JCS(P2)I033) Furan-3-carbaldehyde... 

Treatment of 2,5 and 2,4-furandicarboxylic acids with sulfur tetrafluonde in an excess of hydrogen fluoride leads simultaneously to conversion of the carboxylic groups into trifluoromethyl groups and addition of two fluorine atoms to the furan ring to give highly fluorinated diastereoisomersof2,5-dihydrofuran [225,226,227] (equations 117 and 118)... 

Alkynes substituted with one or two trifluoromethyl groups are also highly reactive dienophiles [9] Indeed, hexafluoro-2-butyne is used increasingly as a definitive acetylenic dienophile in "difficult Diels-Alder reactions. It was used, for example, to prepare novel inside-outside bicycloalkanes via its reaction with cir,trnns -l,3-undecadiene [74] (equation 67) and to do a tandem Diels-Alder reaction with a l,l-bis(pyrrole)methane [75] (equation 68) Indeed, its reactions with pyrrole derivatives and furan have been used in the syntheses of 3,4-bis(tri-fluoromethyl)pyrrole [76, 77] (equation 69) and ],4-bis(trifluoromethyl)benzene-2,3-oxide [78] (equation 70), respectively. 

Allenes carrying trifluoromethyl groups, such as l,l-dichloro-3,3-bis(tn fluoromethyl)allene, undergo facile, room-temperature Diels-Alder reactions with cyclopentadiene (87%) and furan (95%) [94]... 

As the last reaction of equation 99 suggests, trifluoromethyl substituted furans are themselves reactive Diels-Alder dienes [722] (equation 102)... 

Similarly, 1-alkylpyrroles, indoles, furans, thiophenes [60], a-picoline [61], enols, malonates [76], and organometallic compounds [56, 62] react with acyl imines of trifluoropyruvates to give derivatives of a-trifluoromethyl a-amino acids... 

Tetraalkylfurans can be prepared via the Paal-Knorr reaction. For example, Muramatsu synthesized 2,5-diethy]-3,4-bis(trifluoromethyl)furan (72) in 94% yield by treatment of dione 71 with sulfuric acid." ... 

Diels-Alder cycloaddition of 3,4-bis(trifluoromethyl)furan with ethyl propynoate involved addition of two a,/3-unsaturated esters followed by acid-catalyzed ring opening, rearrangement, and elimination of ethanol to give a 6,7-bis(trifluoromethyl)isocoumarin-3-carboxylate [92JFC(56)359]. 

The zinc complex of 1,1,1,5,5,5-hexafluoroacetylacetonate forms coordination polymers in reaction with either 2,5-bis(4-ethynylpyridyl)furan or l,2-bis(4-ethynylpyridyl)benzene. The X-ray crystal structures demonstrate an isotactic helical structure for the former and a syndio-tactic structure for the latter in the solid state. Low-temperature 1H and 19F NMR studies gave information on the solution structures of oligomers. Chiral polymers were prepared from L2Zn where L = 3-((trifluoromethyl)hydroxymethylene)-(+)-camphorate. Reaction with 2,5-bis(4-ethy-nylpyridyl)furan gave a linear zigzag structure and reaction with tris(4-pyridyl)methanol a homo-chiral helical polymer.479... 

For commonly encountered heterocycles, the chemical shifts of trifluo-romethyl substituents will depend somewhat upon where in the heterocycle they are located. Examples of trifluoromethyl derivatives for a number of common heterocycles, including pyridines, quinolines, pyrroles, indoles, thiophenes, benzothiophenes, furans, benzofurans, imidazoles, and uracils are given below. 

Cycloaddition of furans followed by a subsequent transformation is still adopted as a useful strategy to prepare fluorine-containing benzene derivatives and isoquinoline compounds <00SL550>. The cycloaddition adduct can also be converted to a trifluoromethyl substituted cyclohexanone compound via hydrogenation and hydrolysis. Examples of these transformations are illustrated below. 

The use of 2-(hydroxymethyl)furan or 2-(hydroxymethyl)thiophene as aUyhc alcohols gives rise to a-(trifluoromethyl)-a-(2-heteroaryl)glycine derivatives 125 after hydrolysis of the corresponding oxazolone 124 as shown in Scheme 7.35. ... 

Methyl 2-[3-(trifluoromethyl)phenyl]-4/7-furo[3,2-4]pyrrole-5-carboxylate 81a was made by thermolysis of the corresponding methyl 2-azido-3- 5-[3-(trifluoromethyl)phenyl]-2-furyl propenoate 378, which was formed by condensation of 5-[3-(trifluoromethyl)phenyl]furan-2-carbaldehyde 377 with methyl azidoacetate under sodium meth-oxide catalysis (Scheme 40) <2006KGS825>. 

Furan-2,3.4-tricarboxylic acid,155 2-(trifluoromethyl)furandicarboxylic acids.152 and tris(tri-fluoromethyl)-2-furoic acid.156 even in excess hydrogen fluoride and under forcing reaction conditions, give exclusively the corresponding poly(trifluoromethyl)furans. e.g. formation of 14 no addition of fluorine to the ring carbons occurs. 

In the case of furantetracarboxylic acid, the carboxylic acid groups in positions 2 and 5 are converted into trifluoromethyl groups while at positions 3 and 4 they form a cyclic tetrafluoro ether l,l.3.3-tetrafluoro-4,6-bis(trifluoromethyl)-1 //,3//-furo[3.4-c]furan (15) is the sole product.155... 

Sulfur tetrafluoride fluorination of the methyl group has been reported.253 Thus, the reaction with 2,5-dimethylfuran-3,4-dicarboxylic acid gives, besides the expected acid fluoride 16 and 2,5-dimethyl-3,4-bis(trifluoromethyl)furan (17a), higher fluorinated compounds, 2-(difluoro-methyl)-5-methyl-3,4-bis(trifluoromethyl)furan (17b) and 2-methyl-3,4,5-tris(trifluoromethyl)-furan (17c). Low yields are due to considerable tar formation. 

Furan-2,5-dicarboxylic acid reacts similarly, but a temperature of 150°C is required for the reactions to proceed. Again, reaction in the presence of disulfur dichloride gives exclusively the fluorinated product, 2,5-difluoro-2,5-bis(trifluoromethyl)-2,5-dihydrofuran (21), while in the presence of chlorine a mixture of chlorofluoro derivatives 22 and 23 is formed.245... 

Perfluoro ketones and perfluoro a-diketones, with a trifluoromethyl group in the -position to the carbonyl, cyclize in the presence of antimony(V) fluoride to give furan derivatives, as reviewed by Krcspan and Petrov.4 Perfluoro(4-methylpentan-2-one) (1) rearranges to per-fluoro(2,4-dimethyltetrahydrofuran) (2) in 84% yield, when heated in the presence of anti-mony(V) fluoride.5... 

In perfluoro a-diketone 7, which lacks a trifluoromethyl group /i to the carbonyl in the 2-position. it is the carbonyl in the 3-position that participates in the cyclization to form per-fluoro(2-acctyltetrahydrofuran) (8), when 7 is heated at 150 C in the presence of antimony(V) fluoride.5 Perfluoro(2-methyltetrahydropyran-3-one) also rearranges to furan derivative 8 in high yield when heated at 100 C in the presence of antimony(V) fluoride for 20 hours.5... 

IIexene 3.4-Bis-[trifluoromethyl]-oetafluoro-2-oxo- ElOb,. 709 (Oxirano-furan-Ders. A)... 

Furan-2-carboxylic add reacts with sulfur tetrafluoride at 0 °C to give 2-furoyl fluoride, but attempts at further fluonnation results in resin formation [222] A second carboxylic group and/or electron withdrawing substituents, such as the nitro or trifluoromethyl group, stabilize the furan ring Thus, turandicar-... 

---