Electrochemical Fluorination for Preparation of Alkyl Fluorides
Electrochemical fluorinations of organic compounds are classified into three processes: Simons’ process, Philips’ process, and partial (selective) fluorination process.
The Simons’ process is the oldest technique, which is a highly useful route to many perfluorinated organic compounds [1, 2]. A solution or dispersion of organic substrate is electrolyzed at a Ni anode in anhydrous hydrogen fluoride (AHF). The products are mostly perfluorinated, and they are commercially significant materials like perfluoroalkanes, perfluoroacyl fluorides, perfluoroalkanesulfonyl fluorides, perfluorotrialkylamines, and perfluoroalkyl esters. The mechanism of the Simons’ process seems to involve the generation of cationic intermediates and high-valence nickel fluorides.
The Phillips’ process utilizes a porous carbon anode in a molten KF-2HF electrolyte .
The substrate, typically a gas or volatile liquid particularly insoluble in the electrolyte, is introduced through the porous anode and undergoes statistical replacement of hydrogen with fluorine. The products range from monofluoro to perfluoro compounds and include alkane, chloroalkane, carbonyl fluoride, and ester derivatives. The mechanism is believed to involve the generation of elementary fluorine followed by in situ reaction with the organic substrate via a free radical. Thus, this process can be classified as an indirect anodic substitution reaction.
Partial electrochemical fluorination is a rather new method and it is generally carried out in an aprotic solvent containing an organic substrate and a fluoride salt as a supporting electrolyte and a fluorine source [3, 4, 5]. The products are mono- and/or difluorinated compounds, which are formed through the generation of a cationic intermediate followed by reaction with fluoride ions. Therefore, the mechanism is quite similar to other anodic substitution processes.
Electrochemical perfluorination is a process in which all the hydrogen atoms in a starting organic molecule are substituted with fluorine atoms without elementary fluorine generation during electrolysis.
The Simons’ Process
J. H. Simons developed the electrochemical perfluorination of organic compounds in anhydrous liquid HF using nickel electrodes to provide perfluorinated products in the late 1930s, and first published the details in 1949 . He is a pioneer of electrochemical perfluorination and this method is called Simons’ process. The process uses an undivided cell at low temperature to keep HF as a liquid (the boiling point of HF is 19.5 °C).
Another mechanism involves electrogenerated highly oxidized nickel fluorides such as Ni2F5, NiF3 and NiF4 on a nickel anode surface and fluoro complex such as NiF6 2− electrochemically regenerated at the nickel anode. During the electrolysis, partially fluorinated products have polarity and they stay in the electrolyte to be subjected to further electrolysis. The final perfluorinated products are non-polar and their specific density is very high, therefore they precipitate from liquid HF onto the cell bottom as a liquid.
Liquid hydrogen fluoride (anhydrous hydrofluoric acid), which is industrially produced on a large scale, can be used as a fluorine source.
Perfluorinated compounds can be obtained in one step process.
Although the cleavage of carbon-carbon bond in a fluorinating organic compound often takes place in a certain degree during electrochemical fluorination, functional groups in starting materials such as COF, SO2F retain in perfluorinated products.
The yield of perfluorinated organic compounds using Simons’ process is generally low. However, the yield of perfluorinated organic compounds using chemical fluorination reaction is much lower than that using electrochemical fluorination.
Any partially fluorinated compound can be hardly obtained by this process.
A nickel or nickel alloy anode is effective for this process.
Synthetic Aspects of the Simons’ Process
As already mentioned, the yield of perfluorinated products is low since they are usually accompanied by bond cleavage, dimerization, and cyclization. The yield of the desired product generally decreases with increasing carbon chain length.
The Phillips’ Process
This process was developed at Phillips Petroleum Company in Germany [2, 24]. Suitable substrates are at least moderately volatile and not particularly soluble in the molten KF-2HF electrolyte, e.g., alkanes, cycloalkanes, chloroalkanes, acyl fluorides, and esters. It is thought that elementary fluorine is generated as the anode reaction. The anode is porous carbon (not graphite), and the process is thought to involve the electrolytic generation of elementary fluorine and reaction of that fluorine with substrates within the porous carbon anode.
The products appear to be formed by the statistical replacement of substrate hydride with fluoride and range from monofluoro to perfluoro compounds. The electrolysis is run at 90–100 °C. Mechanism of fluorination in this process is “In situ” reaction with fluorine generation, that is, a hydrocarbon substrate reacts with free radicals of fluorine and so this process is classified as indirect fluorination.
The process is efficient for many fluorinations. Different from the Simons’ process, the structure of substrate is retained mostly. For example, ethane is frequently run as a model substrate and various fluoroethanes are formed. Other easily run substrates are 1,2-dichloroethanes (80% retention of 1,2-dichloro structure), acetyl fluoride (85% yield of fluorinated acetyl fluorides), and tetrafluorocyclobutane (90% retention of structure). Current efficiencies are generally rather good (80 ~ 100%). This process is a useful complement to the Simons’ process for many volatile substrates and products.
Process for Perfluorotrimethylamine[(CF3)3N] Production
Perfluorotrimethylamine, (CF3)3N, easily decomposes to release trifluoromethyl radicals, •CF3 which react with organic compounds and promote lipophilicity of the resulting products. It is therefore considered that (CF3)3N is an important fluorine source for synthesis of many useful organofluoro compounds. (CF3)3N is a potential fire extinguish gas, and it is also expected as an etching gas for SiO2 film on Si wafer instead of hexafluoroethane, C2F6, in semi-conductor industry.
Mechanism on fluorination of (CH3)4N+ and (CH3)3N is similar to that in Simons’ process. In the mixed melt of (CH3)3N•mHF and CsF-2.3HF, the highly oxidized nickel fluoride of CsNi2F6 is formed on a nickel anode and it also fluorinates (CH3)3N to form (CF3)3N.
Electrochemical Partial Fluorination
Electrochemical partial fluorination can be commonly achieved in aprotic solvents such as acetonitrile (MeCN), dichloromethane, dimethoxyethane (DME), nitromethane, and sulfolane containing fluoride ions to provide mostly mono- and/or difuorinated products [1, 2, 3, 4, 5]. Electrolyses are conducted at constant potentials slightly higher than the first oxidation potential of a substrate by using a platinum or graphite anode. Constant current electrolysis is also effective for partial fluorination in many cases. Choice of the combination of a supporting fluoride salt and an electrolytic solvent is most important to accomplish efficient selective fluorination because competitive anode passivation (the formation of a nonconducting polymer film on the anode surface that suppresses faradaic current) takes place very often during the electrolysis. Pulse electrolysis is in many cases effective in order to avoid such passivation. Therefore, difficult-to-oxidize fluoride salts, which do not cause the passivation of the anode and have strongly nucleophilic F−, are generally recommended as the supporting fluoride salts. Thus, room temperature-molten salts such as R3N-nHF (n = 3–5), R4NF-nHF (n = 3–5), and pyridine poly(hydrogen fluoride) salt (Py-nHF) are most often used and even R4NBF4 and R4NPF6 salts are effective in some cases [1, 2, 3, 4, 5]. Particularly when a HF supporting salt and a low hydrogen overvoltage cathode such as platinum are used, the reduction of protons (hydrogen evolution) occurs predominantly at the cathode during the electrolysis. Therefore, a divided cell is not always necessary for the fluorination under such conditions.
In an aprotic solvent, F− becomes more nucleophilic; however, the reactivity of F− is quite sensitive to a water-content of the electrolysis system because a hydrated F− is a weak nucleophile. Drying of both the solvent and electrolyte is therefore necessary to optimize the formation of fluorinated products.
Fluorination of Olefins
Anodic fluorination of vinyl sulfides such as 2-(phenylthio)styrene provides vicinal difluorides . 1-Phenylhexene undergoes stereoselective difluorination and fluoroacetamidation upon anodic oxidation in MeCN while the difluorination predominates in the less nucleophilic solvent, dichloromethane (CH2Cl2).
In the case of anodic α-fluorination of toluene, ethylbenzene, and cumene in MeCN, the effciency of the fluorination is in the following order: cumene > ethylbenzene > toluene . On the other hand, the efficiency of acetamidation is reverse. Moreover, triphenylmethane is selectively monofluorinated to provide fluorotriphenylmethane in high yield (80%) even in MeCN . These facts suggest that the more stable benzylic cation intermediate reacts with fluoride ion more efficiently.
Fluorination of Organosulfur Compounds
Regioselective electrochemical fluorination of alkyl ary sulfides having an electron-withdrawing group on the aromatic ring can be also achieved in Et3N-3HF/MeCN .
Fluorination of Other Chalcogeno Compounds
Fluorination of Organic Oxygen, Nitrogen and Halogen Compounds
Fluorination of Other Heteroatom Compounds
Fluorination of Heterocyclic Rings
Dethiofluorination of dithioacetals and thiocarbonyl compounds using chemical oxidising reagents like NBS is a well-established method for the preparation of gem-difluoro compounds. However, this process requires a large amount of oxidizing reagents particularly in a large scale. In sharp contrast, electrochemical dethiofluorination does not require any oxidants.
Solvent-Free Electrochemical Fluorination
Solvent-free electrochemical fluorination is an alternative method for preventing anode passivation and acetoamidation [5, 83]. As already mentioned, handling extremely corrosive and poisonous anhydrous HF in a laboratory setting is accompanied by serious hazards and experimental difficulties. Molten salts such as 70%HF/pyridine (Olah’s reagent) and commercially available Et3N-3HF  are often used to replace anhydrous HF. Other molten salts with the general formula R4NF-nHF (n > 3.5, R = Me, Et, and n-Pr) are useful in electrochemical partial fluorination. These electrolytes are non-viscous liquids that have high conductivity and anodic stability.
Although electrochemical perfluorination has been established and commercialized long time ago, there are some problems like product selectivity and durability of anodes. It is hoped that new electrochemical perfluorination is developed to solve such problems. On the other hand, electrochemical partial fluorination had been unexplored until about 30 years ago. Great progress has been made in this area and various new electrochemical methodologies have been developed for fluorination using various room temperature-molten fluoride salts with and without organic solvents. Highly efficient and selective fluorination of organic compounds using green sustainable methodology is one of the most important goals of modern organofluorine chemistry. It is hoped that electrochemical fluorination will be exploited further and commertialized to produce valuable organofluorine compounds in the near future.
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