Ethers, reactions with fluorinated

Saturated hydrocarbons such as neopentane, notbomane, and cyclooctane have been converted to the corresponding perfluoro derivatives in 10-20% yield by gas-phase reaction with fluorine gas diluted with helium at —78°C. Simple ethers can be completely fluorinated under similar conditions. Crown polyethers can be fluorinated by passing an Fa/He stream over a solid mixture of sodium fluoride and the crown ether. Liquid-phase fluorination of hydrocarbons has also been observed, but the reaction is believed to be ionic, rather than radical, in character. A variety of milder fluorination agents have been developed for synthetic purposes and will be discussed in Chapter 6 of Part B. 

Other limitations of electrochemical fluorination ate that compounds such as ethers and esters ate decomposed by hydrogen fluoride and cannot be effectively processed. Branching and cross-linking often take place as a side reaction in the electrochemical fluorination process. The reaction is also somewhat slow because the organic reactant materials have to diffuse within 0.3 nm of the surface of the electrode and remain there long enough to have all hydrogen replaced with fluorine. The activated fluoride is only active within 0.3 nm of the surface of the electrode. 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

The reactions of some fluorinated ethers may result in the elimination of alkyl fluorides In the case of 2-methoxyperfluoro-2-butene, treatment with antimony pentafluoride gives perfluoro-3-buten-2-one and methylfluoride [107] By reacting 2-chloro-l,l,2-trifluorodiethyl ether with boron trifluoride etherate or with aluminum chloride, chlorofluoroacetyl fluoride can be obtained with the elimination of ethyl fluonde [108] (equations 76 and 77)... 

The fluoride [NS(0)F]3 is more stable thermally and towards nucleophilic reagents than the corresponding chloride. For example, 8.15a is hydrolyzed by water to NH(S02NH2)2, whereas sulfanuric fluoride is unaffected by cold water. In warm water, however, hydrolysis occurs to give the [N3S304F2] anion. All three fluorine atoms in [NS(0)F]3 can be replaced by primary or secondary amines at 80-90°C in the absence of a solvent. Mono- or diphenyl derivatives can be prepared by treatment of [NS(0)F]3 with PhLi in diethyl ether at -70°C, while the Friedel-Crafts reaction with benzene at reflux in the presence of AICI3 gives two isomers of [NS(0)Ph]3. ... 

The small effect on reaction rates of the addition of crown ethers to the lower alcohols was also observed in the reaction of potassium acetate with 1-bromobutane in ethanol (Hirao et al., 1978a,b). The displacement of fluorine in either o-nitro- or p-nitro-fluorobenzene by a methoxy group, by reaction with potassium methoxide in methanol was hardly influenced by the presence of dicyclohexyl-18-crown-6 (Del Cima et al., 1973). Mariani et al. (1978), too,... 

Hashimoto and co-workers (139) further looked at an intermolecular carbonyl ylide cycloaddition screening several different chiral rhodium catalysts. The Hashimoto group chose to study phthaloyl amino acid derivatives for enantiocon-trol of the cycloaddition reactions (Fig. 4.8). Using fluorinated or ethereal solvents with the phthaloyl catalysts gave ee ratios of 20-69%. 

Ethyl bromodifluoroacetate is one of the fluorinated building blocks used most widely. There are scores of examples of the important Reformatsky reaction with aldehydes which occurs in THF/ether solvent mixtures, sometimes under sonication conditions (Eq. 62). 

While fluoroxy compounds react well with enol derivatives, fluorine in general does not. However, there are various reports where such reactions are described and in certain cases even with decent yields. In 1982 it was reported that pyruvates with a dominant enolic form react well with fluorine, to give the corresponding fluoro derivatives l.78 Several silyl enol ethers 2 and 379 including ones made from 1,3-dicarbonyl derivatives 480 react quite satisfactorily with fluorine to give the expected a-fluoro ketones. Steroidal 16-enol acetates react with fluorine to form mainly 16a-fluoro-17-oxo steroids e.g. 5.81... 

Itnino ethers are converted into difluoroamino derivatives, e.g. 9, which are also formed in the reactions with aliphatic amines, but in much lower yields. The yields of N —F product increase when 4-fluorophenylsulfonamide derivatives, e.g. 10, are fluorinated.9... 

The products of the electrochemical perfluorination of aromatic and heteroaromatic compounds are the corresponding perfluorinated cyclic and heterocyclic alkanes.28 and also per-fluorinated derivatives of the heteroaromatic compounds. Perfluorocyclohexane is the principal product from the electrochemical fluorination of benzene and fluorobenzene. Chloro derivatives of perfluorocyclohexane are produced from chlorobenzenes. Anisoles give fully saturated per-fluoro ethers, together with cleavage products. Extensive cleavage is observed in the fluorination of benzenethiols. Chloropyridines, fluorocarbons and sulfur hexafluoride or nitrogen trifluoride are characteristic byproducts from the above scries of reactions. 

The type of products formed in reactions of /(-hydroxy acids with sulfur tetrafluoride depends on the substituents on the carbon alom adjacent to the hydroxy group. Acids such as 3-hy-droxypropanoic acid (21) and 3-hydroxybutanoic acid (22) give, in addition to 1,1,1,3-tetra-fluoroalkanes, mainly dimeric products, i.e. fluorinated esters or ethers, together with small amounts of unsaturated acid fluorides. In contrast, n7C -4,4,4-trifluoro-3-hydroxybutanoic acid (23), depending on the reaction conditions, affords 3,3,3-trifluoro-l-(lrifluoromethyl)propyl fluorosulfite or a mixture of 1,1,1.2,4,4,4-hcptafluorobutanc and l,l,1.4.4,4-hcxafluorobut-2-ene.116... 

Both aromatic and aliphatic fluoroformates 7 can be readily prepared from phenols or alcohols and carbonyl difluoride and treated with sulfur tetrafluoride without isolation. Hydrogen fluoride evolved in the reaction of hydroxy compounds with carbonyl di fluoride serves as a catalyst for the consecutive reaction with sulfur tetrafluoride.15<)-162 This provides a general, convenient, direct synthesis of aryl and alkyl trifluoromethyl ethers 5 from phenols and alcohols. When the intermediate fluoroformate 7 is isolated prior to treatment with sulfur tetrafluoride, at least one mole equivalent of hydrogen fluoride is necessary to promote the fluorination reaction. 159 163 Representative examples of the conversion of hydroxy compounds 6 into trifluoromethyl ethers 5 via intermediate fluoroformates 7 are given (for other examples 7 -> 5, see Houben-Weyl, Vol. E4, pp 628. 629). 

Fhiorination of aromatics. The reagent reacts with toluene to form benzyl fluoride as the major product ( 65% yield). It is also useful for fluorination of phenols- and of alkyl ethers of phenols the or/Ao-isomcr is formed as the major product. Reactions with this reagent thus differ from those with xenon difluoride, which generally favors formation of paro-isomers. 

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