Furan, 2-methyl-, fluorination

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. 

Potassium tetrafluorocobaltate(III) at 200°C reacts with tetrahydrofuran to give82 unsaturated products the major ones are 5 and 6, although the overall yield is poor (< 30%). Furan itself gives no products at all over cobalt(IIl) fluoride it presumably polymerizes. This does not, however, rule furan out as an intermediate in the tetrahydrofuran fluorinations (it could form by desaturation, as does benzene in the fluorination of cyclohexane, vide supra). 2-Methyl-and 2,5-dimethyltetrahydrofuran83 have also been fluorinated with similar results to tetrahydrofuran. 

A large number of fluorinations of partially fluorinated ethers have been successfully carried out. A few examples are fluorination of methyl 2,2,2-trifluoroethyl ether (12),85 1,1,2,2-tetrafluoroethyl 2,2,2-trifluoroethyl ether (13),85 2-(l,l,2,3,3,3-hexafluoropropyl)tetrahydro-furan (14),86 difluoromethyl 2,2,2-trifluoroethyl ether (15),10 and bis(2,2,2-trifluoroethyl) ether (16).10 Manganese(III) fluoride is more reactive than cobalt(III) fluoride in the last two fluorinations. 

Synthetic procedures are available for the preparation of fluoro (e.g., 2-lithio-l-methyl-5-octylpyrrole with fV-fluoro-iV-(phenylsulfonyl)benzenesulfonamide <2003JFC(124)159>), chloro, bromo, and iodo compounds from the corresponding lithio derivatives, for example, 2-iodobenzo[A]furan via lithiation of the heterocycle then reaction with iodine <2002JOC7048>. Perchloryl fluoride (FCIO3), A-chlorosuccinimide, bromine, and iodine are examples of reagents which can be used to introduce fluorine, chlorine, bromine, and iodine, respectively. 

The [4+1] cycloadducts formed from 4,4-bis(trifluoromethyl)-l-oxa-buta-1,3-dienes (92JPR219) and tin(II )-chloride are transformed on heating into 4,4-difluoro-3-trifluoromethylbut-3-en-l-ones, which on treatment with sodium hydride yield 2-fluoro-3-trifluoromethylfurans (92CC348). When heated with phosphorus pentasulfide, l-aryl-4,4-difluoro-3-trifluor-omethylbut-3-en-l-ones give 2-fluoro-3-trifluoromethylthiophenes. The fluorine atom at C—2 of the furans and thiophenes can readily be substituted by a wide variety of nucleophiles (92JPR3II). This reaction sequence represents a preparatively useful method for the selective introduction of biologically relevant substituents into the C—2 position of 3-trifluoro-methyl-substituted furans and thiophenes (Scheme 87). 

An indole 9 and antipyrine (11) were fluorinated to give the respective fluoro derivatives 10 and 12. Attempts to fluorinate furan, pyrrole, N-benzylpyrrole, ethyl 2-thienylacetate, and methyl 2-thiophenecarboxylate with various salts were all unsuccessful owing to excessive tar formation (90JA8563). Porphyrins are efficiently fluorinated at meso positions, and tetrasubstituted derivatives, such as meso-tetraphenylporphyrin, are inert. The preparation of a mixture of fluorinated derivatives 14-18 from 13 and monofluorination of 19 to give 20 are instructive. Interestingly, the products 14-18 were separated into pure components by simple silica gel chromatography (92TL1069). 

The methods of synthesis for bis(perfluoroalkyl)furans are more developed. For example, 2-methyl-3,4-bis(trifluoromethyl)furan can be synthesized by the reaction of 2-methyl-furan-3,4-dicarboxylic with sulfur tetrafluoride. However, the main synthetic methods rely on the use of unsaturated fluorine-containing acyclic compounds. So, 3-trifluoromethylfurans 57 were prepared from p,p-bis(trifluoro-methyl)a,p-unsaturated ketones and tin(II) chloride. ... 

There are several reactions, proceeding with transformation of the fluorine-containing furan cycle. Photochemical transformations of perfluoro-tri and tetra-methyl furans under irradiation by high pressure Hg lamp lead to cyclopropenylcarbonyl derivatives 235. ° No Dewar furan derivatives 236 were detected. 

A good solvent for PLA and for most of the corresponding copolymers is chloroform. Other solvents are chlorinated or fluorinated organic compounds, dioxane, dioxolane and furan. Poly(rac-lactide) and poly(meso-lactide) are soluble in many other organic solvents like acetone, pyridine, ethyl lactate, tetrahydrofuran, xylene, ethyl acetate, dimethylformamide, methyl ethyl ketone. Among non-solvents, the most relative compounds are water, alcohols e.g. methanol, and ethanol) and alkanes e.g. hexane and heptane) [7]. 

The fluorination of perchloro-2,5-dihydrofuran with antimony triiluoride and mixed antimony halides gives all the possible chlorofluoro-2,5-dihydro-furans formed by successive replacement of the allylic chlorine atoms fluorination in anhydrous hydrogen fluoride results in the formation of only trichloro-2,2,5-trifluoro- and dichloro-2,2,5,5-tetrafluoro-2,5-dihydrofuran. Potassium fluoride in iV-methyl-2-pyrrolidone replaces both vinylic and allylic chlorine atoms, giving 2,2,4-trichloro-3,5,5-trifluoro- (5%) and per-fluoro-2,5-dihydrofuran (49%). ... 

Although requiring high temperatures and long reaction times for the fluorination of aromatic compounds, A-fluoro-2,4,6-tri-methyl triflate (2) was also used for the fluorination of estrone, methyl /J-hydroxyphenylacetate, and some heteroaromatic rings such as indoles or antipyrine derivatives. However, furan, pyrrole, A -benzylpyrrole, ethyl 2-thienylacetate, or methyl 2-thio-phenecarboxylate could not be lluorinated with reagent 2. ... 

---