Ether-hydrogen fluoride

Chloro-2,2,2-trifluoroethyl dichloromethyl ether Hydrogen fluoride... 

Amine-Hydrogen Fluoride and Ether-Hydrogen Fluoride Reagents... 

J. Arnold, D. J. Millen. Hydrogen bonding in gaseous mixtures. Part n. Infrared spectra of ether-hydrogen fluoride systems. J Chem Soc 503-509, 1965. 

Anhydrous FeF is prepared by the action of Hquid or gaseous hydrogen fluoride on anhydrous FeCl (see Iron compounds). FeF is insoluble in alcohol, ether, and ben2ene, and sparingly soluble in anhydrous HF and water. The pH of a saturated solution in water varies between 3.5 and 4.0. Low pH indicates the presence of residual amounts of HF. The light gray color of the material is attributed to iron oxide or free iron impurities in the product. 

Preparation. Silver fluoride can be prepared by dissolving Ag20 or Ag2C02 iu anhydrous hydrogen fluoride or aqueous hydrofluoric acid, evaporating to dryness, and then treating with methanol or ether. 

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. 

Depending on the ring substituent, trifluoromethoxyben2enes can be made by the sequential chlorination—fluorination of anisole(s) (351—354). A one-step process with commercial potential is the BF (or SbF2)-cataly2ed reaction of phenol with carbon tetrachloride/hydrogen fluoride (355). Aryl trifluoromethyl ethers, which may not be accessible by the above routes,may be made by fluorination of aryl fluoroformates or aryl chlorothioformates with sulfur tetrafluoride (348) or molybdenum hexafluoride (356). 

Grown Ethers. Ethylene oxide forms cycHc oligomers (crown ethers) in the presence of fluorinated Lewis acids such as boron tritiuoride, phosphoms pentafluoride, or antimony pentafluoride. Hydrogen fluoride is the preferred catalyst (47). The presence of BF , PF , or SbF salts of alkah, alkaline earth, or transition metals directs the oligomerization to the cycHc tetramer, 1,4,7,10-tetraoxacyclododecane [294-93-9] (12-crown-4), pentamer, 1,4,7,10,13-pentaoxacyclopentadecane [33100-27-6] (15-crown-6), andhexamer, 1,4,7,10,13,16-hexaoxacyclooctadecane [17455-13-9]... 

Alkylacetylenes form geminal difluorides by reaction with hydrogen fluoride, neat or in ether solution, at -50 to 0 [7) or by reaction with the pyridinium... 

Phenylacetylene gives 1-phenyI-l, l-difluoroethane on reaction with a large excess of hydrogen fluoride in ether at 0 C or, in better yield, in the gas phase over a mercuric oxide catalyst [/]. Allene affords 2,2-difluoropropane [/]... 

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]... 

In contrast to hydrogen-type ethers, a-haloethers, both linear and cyclic, are relatively easily cleaved by anhydrous hydrogen fluoride. Bis( 1,1 -difluoroalkyl) ethers are converted to 1,1,1 -trifluoroalkanes and alkanoyl fluorides The cleavage temperature depends on the substituents present ethers having no electronegative substituents other than a-fluorines are readily cleaved below 20 °C, 3-halo-1,1-di fluoroethers require approximately 70 °C, but 2-halo-1,1-difluoroethers are prac tically resistant toward hydrogen fluoride [/I (equation 1)... 

A nonconventional synthesis of the known inhalation anaesthetic, 2-bromo-2 chloro-l,l,l-trifluoroethane (Halothane), based on the reaction of ethyl 1,2 di bromo-1,2-dicliloroethyl ether with anhydrous hydrogen fluoride and sulfur tetrafluoride, has been patented The reaction presumably involves cleavage of the ether linkage, followed by fluorination of the intermediate bromochloroacetyl halide with sulfur tetrafluoride, ethyl halides are the by-products [2] (equation 2)... 

Nonfluorinated a- and P diketoms give the corresponding tetrafluoroalkanes as the major products together with considerable amounts of alkenes, ethers, and sulfites Formation of side products is reduced, and yields of tetrafluoroalkanes are greatly improved by conducting the lluori nation reactions in an excess of anhydrous hydrogen fluoride [176, 177]... 

Diphenylperfluoropentan-l, 5-dione, m contrast to its shorter chain homo-logue, which gives the normal fluonnation product, on treatment with sulfur tetrafluoride and hydrogen fluoride torms a cyclic ether as the only product [178] (equation 90)... 

The total yield of products from alkanecarboxyhc acids increases, in most cases, by addition of anhydrous hydrogen fluoride. The optimum hydrogen fluoride concentration is much higher than catalytic and is related to the basicity of a carbonyl group. A mechanism for the formation of both 1,1,1-trifluoroalkanes and bis(l,l-difluoroalkyl) ethers has been proposed [206] (equation 102)... 

Chlorine monofluoride m a hydrogen fluoride solution reacts rapidly at low temperature with haloacetate and halopropanoate esters to give 61-80% yields of a a difluoroalkyl ethers [242] (equation 128)... 

In the onginal route to isoflurane, the methyl ether of tnfluoroethanol is made with dimethyl sulfate [.S] followed by careful chlorination of the methyl group to make the dichloromethyl ether. This ether is fluorinated with hydrogen fluoride and an antimony catalyst and the final step is monochlorination of the a carbon of the ethyl group [S] (equation 2)... 

Preparation of 9a-Fluoro-110,17a,21-Trihydroxy-160-Methyl-4-Pregnene-3,2O-Dione 21-Acetate To a solution of 200 mg of 9(3,11(3-epoxy-1 7a,21-dihydroxy-16(3-methyl-4-pregnene 3,20-dione 21-acetate in 2 ml of chloroform and 2 ml of tetrahydrofuran in a polyethylene bottle at -60°C was added 2 ml of a 2 1 (by weight) mixture of anhydrous hydrogen fluoride and tetrahydrofuran. After 4 hours at -10°C the mixture was cooled to -60°C and cautiously added to a stirred mixture of 30 ml or 25% aqueous potassium carbonate and 25 ml of chloroform kept at -5°C. The aqueous phase was further extracted with chloroform and the latter phase washed with water and dried over magnesium sulfate. The residue on crystallization from acetone-ether gave pure 9a-fluoro-11(3,17a,21-trihydroxy-16(3-methyl-4-pregnene-3,20-dione 21-acetate. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

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