Hydrogen fluoride electrochemical fluorination

Electrochemical Fluorination. In the Simons electrochemical fluorination (ECF) process the organic reactant is dissolved in anhydrous hydrogen fluoride and fluorinated at the anode, usually nickel, of an electrochemical ceU. This process has been reviewed (6). Essentially all hydrogen atoms are substituted by fluorine atoms carbon—carbon multiple bonds are saturated. The product phase is heavier than the HF phase and insoluble in it and is recovered by phase separation. 

Replacement of Hydrogen. Three methods of substitution of a hydrogen atom by fluorine are (/) reaction of a G—H bond with elemental fluorine (direct fluorination, (2) reaction of a G—H bond with a high valence state metal fluoride like Agp2 or GoF, and (J) electrochemical fluorination in which the reaction occurs at the anode of a cell containing a source of fluoride, usually HF. 

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. 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

Various fluorinations, which need principally much energy for the generation of the reagent fluorine, are carried out electrochemically in liquid hydrogen fluoride, even in an industrial scale [66]. Owing to the extreme toxicity and the corrosive medium, special precautions are necessary. 

Electrochemical fluorination in anhydrous hydrogen fluoride (Simons process) involves electrolysis of organic compounds (ahphatic hydrocarbons, haloalkanes, acid halides, esters, ethers, amines) at nickel electrodes. It leads mostly to perfluori-nated compounds, but is accompanied to a high extent by cleavage and rearrangement reactions. The mechanism of the formation of carbocations according to Eq. (1) and Scheme 1 is assumed... 

The three principal electrochemical methods are described by which fluorine can be directly introduced into organic compounds, namely electrolysis in molten salts or fluoride ion solutions, electrolysis in molten potassium fluoride/hydrogen fluoride melts at porous anodes, and electrolysis in anhydrous hydrogen fluoride at nickel anodes. Using examples from the past decade, it is aimed to demonstrate that electrofluorination in its various forms has proved to be an increasingly versatile tool in the repertoire of the synthetic chemist. Each method is described in terms of its essential characteristics, reaction parameters, synthetic utility, advantages and disadvantages, patent protection, and potential for commercial exploitation. The different mechanisms proposed to explain each process are critically reviewed. 

In a later publication [ 129], using the same equipment, Liu et al. describe process improvements in the electrochemical fluorination of octanoyl chloride in which formation of polymeric tar at the anode surface was limited by addition of a mercaptan (1-methyl-1-propanethiol), and by constant current density operation (7 mA cm-2). Continuous operation was achieved by frequent additions of a solution of reactant in hydrogen fluoride. Conversion of reactant to perfluori-nated products was increased to 80%, with good selectivity. 

Meinert and others [85] have stated that their concept for the electrochemical fluorination of organic compounds is based on the assumption that the first step is the anodic oxidation of the organic molecule. The electrochemical process is promoted by weakening of the C-H bonds due to hydrogen-fluorine bridges. After anodic withdrawal, the C-F bond is formed by insertion of a fluoride ion, present in the Helmholtz-double-layer at the electrode surface. 

Various fluorine compounds, such as xenon(II) fluoride, act under certain conditions (irradiation, gas-phase reaction) as radical fluorinating agents. Electrochemical fluorinations (see Section 7.) carried out in hydrogen fluoride containing systems (ref 7, pp73-76) are further examples of radical-type reactions. 

Formal replacement of hydrogen by fluorine takes place in the a-position of a ketone by treatment of enol acetates with triethylamine tris(hydrogen fluoride).51-55 The kinetically favored isomers are formed.51,55 Furthermore, benzylic positions bonded with an electron-withdrawing group (ketone, ester, nitrile, sulfonate) can be fluorinated electrochemically.51" 6-58 There are also various examples of the preparation of a-fluorosulfides front sulfides.51... 

Partial electrochemical fluorination is conducted in organic solvents instead of anhydrous hydrogen fluoride. The obtained products are mostly monofluorinated compounds. The partially fluorinated products are separated from the electrolytes by distillation or extraction. 

The electrochemical oxidation of bromoalkanes on platinum in anhydrous hydrogen fluoride displaces bromine by fluorine.27... 

Electrochemical oxidation of alkyl aryl ethers results in oxidative dealkylation and coupling of the intermediate radicals. Electro-oxidation of alkyl (4-fluorophenyl) ethers in the presence of a hydrogen fluoride double salt leads to 4,4-difluorocyclohexa-2,5-dienone in 50% yield (Table 10).182 In the electrochemical oxidation of methyl tetrafluorophenyl ethers with a hydrogen atom at the para position, coupled products 6 arc obtained.183 If the para position in the substrate is occupied by a fluorine substituent, then no reaction occurs. 

All methods that have been used successfully for producing fluorine in quantity are electrochemical and make use of the system hydrogen fluoride-potassium fluoride in different forms of cells and at various temperatures. Cady1 has shown by a study of the freezing points and vapor pressures of this system that there are three regions where electrolysis to produce fluorine is practicable. In each of these regions, the system is liquid, and the vapor pressure of hydrogen fluoride is below atmospheric pressure. 

Electrochemical fluorination 168,169> is a commercial process for perfluorina-tion of aliphatic compounds. The reaction is performed in liquid hydrogen fluoride -potassium fluoride at a nickel anode. The mechanism is not known free fluorine cannot be detected during electrolysis, so it seems probable that fluorination is a direct electrochemical reaction. Theoretically, hydrogen fluoride-potassium fluoride should be a very oxidation-resistant SSE, and it might well be that the mechanism is analogous to that proposed for anodic acetamidation of aliphatic compounds in acetonitrile-tetrabutylammonium hexafluorophosphate 44 K... 

The electrochemical and chemical stability of diamond makes it an ideal electrode material for electrochemical fluorination reactions. The installation of fluorine a to heteroatom-substituted positions can be anodically performed by hydrogen fluoride/triethylamine mixtures. The Fuchigami group studied several electrode materials for the fluorination of oxindole 20. In this transformation to 21 only a... 

Other reagents, such as bromine monofluoride, generated in situ from A -bromosuccinimide and pyridinium poly(hydrogen fluoride) [NBS, (HF) /pyridine] or poly(4-vinylpyridinium) poly(hydrogen fluoride) [NBS, (HF) /PVP], and elemental fluorine, as well as electrochemical methods, have been described for the transformation of hydrazones into. gem-difluoro compounds. 

Not only aryl fluorides can be prepared from trimethylsilanes. Regioselective electrochemical fluorination of4-(trimethylsilyl)azetidin-2-ones 10 to give 11 has also been reported (Table 5). The electrolyses of compounds 10 are carried Out using acetonitrile as solvent. The best yields of fluorinated compounds (Table 5) are obtained when triethylamine trishydrofluoride is used as the fluorine source (with hydrogen fluoride/pyridine and triethylamine bishydro-fluoride lower yields are obtained). The stereochemistry of alkylidene side chains (Table 5, entries 3 and 4) is retained during the electrolyses. High stereoselectivity is observed in some cases (Table 5, entry 6). 

The electrochemical fluorination of alkenes in anhydrous hydrogen fluoride is another possibility for the addition of fluorine to unsaturated compounds, but the yields are poor to moderate and the difluoro addition products are only byproducts. 

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