Highly selective electrochemical fluorination of organic compounds in ionic liquids

Recent studies on electrochemical partial fluorination in ionic liquid fluoride salts are reviewed. At first, historical background and some problems of electrochemical fluorination in organic solvents are briefly mentioned. Solvent-free electrochemical fluorinations in ionic liquids are explained as follows. Ultrasonication was found to improve both the yield and current efficiency for electrochemical fluorination of α-phenylthioacetate, which is mainly attributable to marked mass transport promotion of the substrate and the suppression of anode passivation. Highly regioselective and efficient fluorination of cyclic ethers, lactones, and cyclic carbonate was achieved in Et₄NF·4HF and Et₃N·5HF. Selective fluorination of hardly oxidizable phthalide was realized using a combination of imidazolium and fluoride ionic liquids. The unique effect of imidazolium ionic liquids on electrochemical fluorodesulfurization of 3-phenylthiophthalide was explained. Reuse of ionic liquids for electrochemical fluorination is also possible.     

Unique solvent effects on selective electrochemical fluorination of organic compounds

Recent studies on solvent effects on electrochemical partial fluorination are reviewed. At first, the historical background and some problems of electrochemical fluorination in organic solvents like acetonitrile (MeCN) are briefly mentioned. Ethereal solvents like dimethoxyethane (DME) and a mixture of DME and MeCN were found to improve both the yield and current efficiency for electrochemical fluorination since these solvent systems effectively suppress anode passivation and overoxidation of fluorinated products once formed during the electrolysis. It was also found that DME stabilizes radical cationic intermediates of 4-arylthio-1,3-dioxolan-2-ones and 3-phenylthiophthalide leading to α-fluorination while dichloromethane (CH₂Cl₂) destabilizes them leading to fluorodesulfurization. On the other hand, imidazolium ionic liquids and liquid fluoride salts like Et₄NF·4HF and Et₃N·5HF exhibited similar effects to CH₂Cl₂. Selective fluorination of hardly oxidizable phthalide was also achieved using a combination of two kinds of ionic liquids (imidazolium triflate and liquid fluoride salts).     

Production of MoF6 via electrochemical fluorination

A new process for the electrochemical preparation of the fluorinating agent MoF₆ is described. Solutions fo MoF₄ in anhydrous HF are electrolyzed in a multielectrode cell at 20°C, 5.4÷5.7V cell voltage and 50÷100 A/m² current density, using nickel anodes and cathodes. A new modified Simons cell has been designed, equipped with a stirring system for the efficient recirculation of the electrolyte and with a condenser held at ?15°C.The reaction product MoF₆ (b.p. 35°C) dissolves in the electrolyte, contributing to its conductivity and in part is volatilized together with HF and some byproduct fluorine.Gaseous MoF₆ passing beyond the condenser can be easily collected and separated in a nickel trap held at low temperature.The process presents substantial advantages in comparison with known alternatives, such as the synthesis of MoF₆ from the elements Mo and F₂ at 250°C or the dismutation reaction: 2MoCl₅ + 10HF → MoF₄ + MoF₆ + 10 HClPreparation of the starting material MoF₄, operating conditions and experimental results are illustrated.     

Advances in fluorination of organic compounds with sulphur tetrafluoride

Sulphur tetrafluoride has been known since 1958 as an efficient fluorinating agent for replacing oxygen atoms in carbonyl groups by fluorines. In the past fifteen years a number of new reactions of sulphur tetrafluoride with carbonyl compounds have been discovered. These include formation of bis(1,1-difluoroalkyl) ethers from alkanecar☐ylic acids, bis(1-fluoroalkyl) ethers from aliphatic aldehydes, and cyclic fluoroethers from difunctional car☐ylic acids and aldehydes. In the reactions with branched aldehydes rearrangements of hydrogen and fluorine atoms and also of the carbon skeleton were observed. Tertiary amides were successfully converted to 1,1-difluoroamines and tertiary formamides to trifluoromethylamines. This last reaction involves simultaneous fluorination of the carbon-oxygen and carbon-hydrogen bonds.Participation of carbocations in the mechanism of fluorination of carbonyl groups has been proved and a revised mechanism proposed. Evidence for a reduction-oxidation mechanism for the replacement of formyl hydrogen by fluorine has also been found.     

Electrolytic partial fluorination of organic compounds. Part 78: Regioselective anodic fluorination of 2-oxazolidinones

Various 2-oxazolidinones were galvanostatically electrooxidized in the presence of various fluoride salts. It was found that a fluorine atom was introduced to the α-position of the nitrogen atom of N-acyl- and N-alkoxycarbonyl-2-oxazolidinones to provide the corresponding α-fluorinated products in moderate to good yields. In the case of N-phenoxycarbonyl derivative, fluorination took place on the phenyl group selectively.     

Selective electrochemical fluorination of organic molecules and macromolecules in ionic liquids

This article provides an outline of recent studies on selective electrochemical fluorination in ionic liquid fluoride salts toward green sustainable chemistry. First, a brief historical background of electrochemical fluorination in organic solvents is provided, and some particular problems and unique solvent effects associated with this technique are briefly mentioned. Second, recent progress in selective fluorination and fluorodesulfurization of organic molecules and macromolecules in ionic liquids using direct and indirect electrolysis with recyclable mediators is reviewed.     

The electrochemical fluorination of acetyl fluoride

The electrochemical fluorination of acetyl fluoride in anhydrous hydrogen fluoride to produce trifluoroacetyl fluoride was investigated in a microprocessor-aided modified Simons' reactor. The product was recovered in acetic acid as trifluoroacetic acid. The experiments were carried out at a controlled anodic potential using a Cu/CuF₂ reference electrode. Product yields of 36 - 45%, current efficiencies of 30 to 50% and energy efficiencies of 11 – 23% were obtained.Experimental results of this investigation are presented and discussed.     

Electroytic partial fluorination of organic compounds. 52. Regio- and diastereoselective anodic fluorination of thiazolidines

Anodic fluorination of N-benzoyl, N-acethyl-, and N-formylthiazolidine derived from L-cysteine was carried out in dimethoxyethane (DME) and acetonitrile containing various supporting fluoride salts using an undivided cell. Highly regioselective fluorination proceeded to provide the corresponding 5-monofluorinated thiazolidine derivatives in good yields in DME, and the diastereoselectivitiy was moderate to high regardless of the supporting fluoride salts. The diastereoselectivitiy of the fluorination was greatly affected by the bulkyness of the subsitituent on the nitrogen atom, and N-benzoylthiazolidine gave much higher diastereoselectivity compared with N-formyl derivative. The fluorination of the thiazolidines was not achieved by commercially available fluorinating reagents such as N-fluoropyridinium salts.     

The electrochemical methoxylation of methoxybenzenes and related compounds : The mechanism of electrochemical methoxylation of 1,4-dimethoxybenzene

Anodic oxidation of benzenoid aromatic ethers in methanolic KOH soln at a platinum electrode constitutes a one step method for the synthesis of the rare class of compounds, herein designated as the quinone diketals. The mechanism of conversion of 1,4-dimethoxybenzene to the diketal of p-benzoquinone, based on the evidence accumulated, is considered to proceed via discharge of the adsorbed aromatic compound, followed by nucleophilic reaction of the solvent system with the electrogenerated cationic species. The quinone diketal products resulting from anisole, 1,4-, 1,2-, and 1,3-dimethoxybenzene, 9,10-dimethoxyanthracene and benzodioxane have been established. In contrast methyl benzoate, anisonitrite, and benzene were found to be unreactive in agreement with a direct discharge scheme which does not involve methoxy radicals.     

Electrolytic partial fluorination of organic compounds. 83. Anodic fluorination of N-substituted pyrroles and its synthetic applications to gem-difluorinated heterocyclic compounds

Anodic fluorination of N-substituted pyrroles was carried out in MeCN containing supporting fluoride salts such as Et3N-nHF (n = 2-5) and Et4NF-4HF with use of platinum electrodes under constant current conditions. Anodic fluorination of N-methyl- and N-p-tosylpyrroles having an electron-withdrawing cyano group proceeded smoothly to provide the corresponding fluorinated products in moderate to excellent yields, while anodic fluorination of N-methylpyrrole devoid of an electron-withdrawing cyano group did not take place and a polymeric product was formed at the anode surface. In sharp contrast to the cases of N-methylpyrroles, even N-p-tosylpyrrole devoid of an electron-withdrawing cyano group underwent anodic fluorination efficiently. Diels-Alder reaction of 5,5-difluoro-1-methyl-3-pyrrolin-2-one (2e) derived from anodic fluorination of 2-cyano-1-methylpyrrole (2a) with various dienes was carried out to provide the cycloaddition products in excellent yields. Furthermore, Michael reaction of 2e with various nucleophiles was also successfully carried out to provide the Michael addition products in good to excellent yields.     

Selective and effective fluorination of organic compounds in water using Selectfluor F-TEDA-BF4

[reaction: see text] Selective and effective fluorination of various types of organic compounds performed in water as the reaction medium using 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor F-TEDA-BF4) is reported. 2-Naphthole and 2-methoxynaphthalene were thus transformed to 1,1-difluoro-2(1H)naphthalenone, estrone to 10beta-fluoro-1,4-estradien-3,17-dione, phenyl-substituted alkenes to vicinal fluorohydrins, and various ketones, 1,3-diketones, or beta-ketoesters to corresponding alpha-fluoro or alpha,alpha-difluoro ketones.     

Sonochemical fluorination of heterocyclic nitro compounds with Selectfluor™ (F-TEDA-BF4)

CH and CH₂ groups attached to a heterocycle and a nitro function were rapidly mono- or difluorinated by reaction with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis-tetrafluoroborate (Selectfluor) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), preferably with ultrasonic irradiation.     

Electrolytic partial fluorination of organic compounds 84: Anodic mono- and difluorination of benzylphosphonate derivatives

Anodic fluorination of benzylphosphonate derivatives was carried out under various electrolytic conditions to provide the corresponding α-mono- and/or α,α-difluoro-products in moderate to good yields. It was found that the selectivity of fluorinated products was depending on the molecular structures of the starting substrates and the electrolytic conditions.     

Electrolytic partial fluorination of organic compounds.71. Highly diastereoselective anodic fluorination of sulfides having oxygen-containing heterocyclic groups

Diastereoselective anodic fluorination of sulfides having various oxygen-containing heterocyclic substituents such as 2-furanyl, 1,3-dioxolanyl, 2,2-dimethyl-1,3-dioxolanyl, 2-spirocyclohexyl-1,3-dioxolanyl, 2-spiroadamantyl-1,3-dixolanyl, and 1,3-dioxolanonyl groups at the beta-position was comparatively studied. Among the oxygen-containing heterocyclic substituents, the 2-spirocyclohexyl-1,3-dioxolanyl group gave the best diastereoselectivity (80% de). The diastereoselectivity was also affected by supporting fluoride salts and solvents. Chemical fluorination using selectfluor resulted in much lower diastereoselectivity and extremely poor yield. The fluorinated products were readily converted into the corresponding fluorinated diol in good yields by acidic hydrolysis.     

Detection of free radicals in electrochemical fluorination

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 255–256, January, 1991.     

The electrochemical fluorination of octanoyl fluoride with electrolyte circulation

A modification to the standard method of electrochemical fluorination is described which embodies a forced flow of electrolyte through the electrode pack. A preliminary study of flow characteristics through an electrode pack was carried out.Good yields of perfluorooctanoyl fluoride and associated perfluorinated products are reported. The nature of the anode surface was studied before and after fluorination by scanning electron microscopy.     

The fluorination of organic substrates with tetraphenyl-phosphonium hydrogendifluoride

Tetraphenylphosphonium hydrogendifluoride acts as a powerful source of F^? in various reactions with organic substrates to give fluorine containing-products     

Pi-conjugated N-heterocyclic compounds: correlation of computational and electrochemical data

Electrochemical reduction potentials of a broad selection of nitrogen-containing molecules suitable as bridging (dipodal and tripodal) ligands in coordination and organometallic chemistry are reported and compared with results of semiempirical calculations. Trends of electrode potentials observed experimentally agree with respective calculated data, deviations can be explained by invoking peculiarities of the involved molecular orbitals and ligand-electrode surface interactions.     

The “Base-catalysed” fluorination of SO2 by XeF2

The fluorination of SO₂ by XeF₂ in the presence of compounds of the type MX (M = NMe₄, Cs, K; X = F, Cl) is described.Reaction mechanisms are proposed in which the XeF₂ functions as a weak Lewis acid.