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).     

Selective anodic fluorination of electrophilic alkenes

Anodic fluorination of some electrophilic alkenes (conjugated with electron-withdrawn groups), ethyl cinnamates, RC₆H₄CHCHCO₂Et (R = H, CH₃, CH₃O, F and CF₃), cinnamonitrile, C₆H₄CHCHCN, phenyl stryryl ketone, and t-butyl styryl ketone using ammonium fluorides as the fluorine source and supporting electrolyte, in CH₂Cl₂ as electrolytic solvent yields the expected vicinal difluoro compounds, as mixture of erythro and threo isomers. The anodic fluorination of phenyl 3,5-di-t-butyl-4-hydroxystyryl ketone yields two monofluoro compounds. A possible reaction mechanism is discussed.     

Oxidative fluorination of aromatic compounds in liquid hydrogen fluoride

Toluene derivatives bearing electronegative substituents are cleanly fluorinated on the methyl group by reaction with lead dioxide or nickel dioxide in liquid HF. For example, 4-nitrotoluene gives in high yield a mixture of 4-nitrobenzyl fluoride and 4-nitrobenzal fluoride. Aromatic cation radicals are proposed as intermediates.     

Comparison of chaotropic salt and ionic liquid as mobile phase additives in reversed-phase high-performance liquid chromatography of biogenic amines

Highly hydrophilic compounds belonging to biogenic amines were analysed in the reversed-phase system, modified with the addition of ionic liquids: 1-ethyl-3-methyl-imidazolium hexafluorophosphate (EMIM PF(6)) and chaotropic salt NaPF(6) on Discovery HS C18 column at acidic conditions. The effect of the additives concentration and the presence of organic solvent on the analytes' chromatographic parameters such as retention factor, tailing factor and theoretical plates number were all determined. On the basis of k versus ionic liquid concentration in aqueous-organic mobile phase with constant amount of phosphate buffer, retention mechanism was studied. It was established that the presence of organic solvent with low dielectric constant and ionic liquid with both chaotropic ions allows achieving typical Langmuir shape of this relationship. Investigated mobile phase additives are comparable according to efficiency and selectivity towards biogenic amines analysis. However, the sensitivity was found to be better for the eluent system modified with chaotropic salt.     

A novel glycosidation of glycosyl fluoride using a designed ionic liquid and its effect on the stereoselectivity

The glycosidations of glucopyranosyl fluoride and alcohols using an ionic liquid containing a protic acid effectively proceeded under mild conditions to afford the corresponding glycosides in good to high yields. The stereoselectivity of the glycosidation was significantly affected by the ionic liquid solvent. 1-n-Hexyl-3-methylimidazolium trifluoromethanesulfonate (C₆mim[OTf]), containing a trifluoromethanesulfonate anion, and 1-(3-cyanopropyl)-3-methylimidazolium trifluoromethanesulfonimidide (CNC₃mim[NTf₂]), possessing a cyano group at the side chain of the imidazolium cation, gave the β-stereoselectivity.     

Morphology-controlled synthesis of nanostructured zinc hydroxide fluoride via a microwave-assisted ionic liquid route

Zinc hydroxide fluoride (Zn(OH)F) with multiform morphologies such as flower-like particles, pumpkin-like aggregates, and hollow orange-like aggregates are prepared by a microwave-assisted ionic liquid method. During synthesis, microwave irradiation accelerates the reaction rate and shortens the reaction time. 1-Butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF₄]) or 1-2-hydroxylethyl-3-methylimidazolium tetrafluoroborate ([C₂OHmim][BF₄]) is used as both reactant and template. Experimental results indicate that the morphology evolution of Zn(OH)F is mainly controlled by the concentration of zinc acetate solution. A possible mechanism underlying the formation of nanostructured Zn(OH)F with diverse morphologies is proposed. Furthermore, nanoporous ZnO is obtained by the thermal decomposition of as-prepared Zn(OH)F in air, and the morphology is well retained.     

Electrochemical fluorination (Simons process) – A powerful tool for the preparation of new conducting salts, ionic liquids and strong Brønsted acids

Electrochemical fluorination (Simons process) provides a cheap commercial access to a series of tris(perfluoroalkyl)diflurophosphoranes. These substances are convenient starting material for the preparation of various fluoro-chemicals. The synthesis of new conducting salts and ionic liquids with perfluoroalkyl-fluorophosphate (FAP) and perfluoroalkyl-phosphinate anions is described. FAP ionic liquids exhibit excellent hydrolytic stability, low viscosity and high electrochemical and thermal stability. Organic and inorganic salts with FAP anions possess high electrochemical stability and conductivity that makes them attractive for application in several electrochemical devices (Li-ion batteries, super-capacitors, etc.). The possible application of H[(R_F)₃PF₃] (HFAP), (R_F)₂P(O)(OH) and (R_F)P(O)(OH)₂ as components of proton-conducting membranes is discussed.     

Hydrophosphonylation of activated alkenes and alkynes via fluoride ion activation in ionic liquid medium

A simple transition metal-free hydro/hydrothiophosphonylation of Baylis-Hillman adducts, substituted allyl bromides, allenylphosphonates and alkynes, promoted by fluoride ion in ionic liquid, is described. Clear-cut evidence for fluoride activation of the phosphite via pentacoordinate phosphorus is provided for the first time. Also, in a comparative reaction, the product obtained was different from that from the palladium catalyzed one. Structures of key products are proven by X-ray crystallography.     

Ionic cyclodextrins in ionic liquid matrices as chiral stationary phases for gas chromatography

Ionic liquids (ILs) are used to dissolve ionic cyclodextrin (CD) derivatives to produce a new type of gas chromatographic chiral stationary phase. Compared to a previous study with neutral cyclodextrin chiral selectors, the new ionic liquid-based stationary phase exhibits broader enantioselectivities, up to seven times higher efficiencies, and greater thermal stabilities. When compared to the analogous commercial column with polysiloxane matrix, it exhibits different enantioselectivities, more symmetric peak shapes and some complementary enantioseparations. The most profound separation enhancements are usually found for more polar analytes.     

Thermal stability of ionic liquid BMI(BF4) in the presence of nucleophiles

We have found that a common ionic liquid--one containing a N-N′-dialkylimidazolium cation--decomposes in the presence of nucleophiles at much lower temperatures than previously believed. The decomposition occurs through S_N2 attack of the nucleophile on the electrophilic alkyl groups attached to the imidazolium ring.     

Increased paraoxon detection by acetylcholinesterase inactivation with ionic liquid additives

This is the first study using ionic liquids (ILs) as additive in the aqueous solvent medium for detection of paraoxon by acetylcholinesterase inhibition method. A systematic comparison of various ILs with organic solvents has been made. The aqueous buffer solution containing ionic liquid ethylpyridinium hexafluorophosphate [EtPy]⁺[PF₆]⁻ has been found to give the best results. The inhibition kinetic follows the first order model. Ionic liquids modified aqueous solutions show the potential to provide a promising and effective medium in detection of paraoxon with acetylcholinesterase.     

Facile and highly efficient synthesis of fluorinated heterocycles via Prins cyclization in ionic liquid hydrogen fluoride salts

Prins cyclization of homoallylic alcohols, thiols, and amines with various aldehydes in an ionic liquid HF salt (Et(4)NF.5HF) afforded the corresponding 4-fluorinated heterocycles in excellent yields.     

Effects of additives on the cloud points of selected nonionic linear ethoxylated alcohol surfactants

Effects of various additives including inorganic salts, nonionic and ionic surfactants, water-soluble polymers and alcohols on the cloud points of three linear nonionic surfactants, Tergitol 15-S-7, Tergitol 15-S-9 and Neodol 25-7, were investigated. These surfactants are readily biodegradable and either linear primary or secondary ethoxylated alcohols. Cloud points of these surfactants were functions of their concentrations and concentrations of additives. The cloud points of nonionic surfactant mixtures lay in between the cloud points of individual component surfactants. Presence of two ionic surfactants, sodium dodecyl sulfate (SDS) and cetyl trimethyl ammonium bromide (CTAB), increased the cloud point of 1 wt% Tergitol 15-S-7 micellar solution dramatically when concentrations of ionic surfactants approaching their critical micelle concentration. Addition of water-soluble polymers decreased the cloud point, while addition of inorganic salts can either increase or decrease the cloud points. However, the effect of an alcohol additive on cloud point was dependent on its chain length or its water solubility. Interestingly, synergistic effects between sulfate or phosphate and pentanol on depression of cloud points of Tergitol 15-S-9 were discovered. A linear model predicting cloud points of Tergitol 15-S-X (X = 7, 9 and 12) surfactants and Neodol 25-X (X = 7, 9 and 12) surfactants were proposed with a correlation to logarithm of their ethylene oxide numbers.     

Effective reductive amination of carbonyl compounds with hydrogen catalyzed by iridium complex in organic solvent and in ionic liquid

The direct reductive amination (DRA) of carbonyl compounds with amines has been achieved using homogenous iridium catalyst and gaseous hydrogen. It appeared that the cationic iridium catalyst, [Ir(cod)₂]BF₄, without any other ligands was sufficient for the reaction. For the DRA of the ketone substrates, an ionic liquid, [Bmim]BF₄, was found to be superior to the other organic solvent used. Especially, the counter anion of the ionic liquid has a significant influence on the selectivity, and at the same time, a high reaction temperature was found to be crucial for the excellent selectivity.     

Facile nucleophilic fluorination by synergistic effect between polymer-supported ionic liquid catalyst and tert-alcohol reaction media system

A highly efficient method was developed for nucleophilic fluorination using an alkali metal fluoride through the synergistic effect of the polymer-supported ionic liquid (PSIL) as a catalyst and tert-alcohol as an alternative reaction media. This PSIL/tert-alcohol system not only enhances the reactivity of alkali metal fluorides and reduces the formation of by-products but also allows the use of a polymer-supported catalyst protocol. As an example, the nucleophilic fluorinations of the model compound, 2-(3-bromopropoxy)naphthalene, with CsF using only tert-amyl alcohol as solvent (for 2 h reaction time), 0.5 equiv of PS[hmim][BF₄] in CH₃CN (for 12 h reaction time), and 0.5 equiv of PS[hmim][BF₄] in tert-amyl alcohol (which is a PSIL/tert-alcohol system for the synergistic effect; for 2 h reaction time) provided 18, 40, and 84% yield, respectively. The characteristics of the nucleophilic fluorination reactions of some halo- and alkanesulfonyloxyalkane systems to the corresponding fluoroalkanes using various alkali metal fluorides are also reported.     

Influence of the ionic liquid structure on thiophene solubility

Binary liquid-liquid equilibria for 10 systems containing an ionic liquid with thiophene were measured by dynamic method in the temperature range from 283 K to the boiling point of thiophene. The influence of ionic liquid structure on solubility of thiophene is discussed in comparison with results taken from the literature. The solubility of thiophene in all investigated ionic liquids is high - below 0.31 ionic liquid mole fraction.     

A novel ionic liquid based on small size cation

An ionic liquid material containing small size cation was synthesized and its composition and structure was determined by FT-IR, 1H NMR, 13C NMR and element analysis. However, its physical properties such as melting point, viscosity, conductivity, etc. were measured and the results show that the novel ionic liquid is composed of small cation with highly symmetry and larger anion which is very rare among the reported ionic liquid family.     

A synthesis of diethyl alkylsulfanylmethylmalonates catalyzed by KOH in an ionic liquid

Abstract  1-Ethyl-3-methylimidazolium bromide was used as a green recyclable alternative to volatile organic solvents for KOH catalyzed three-component synthesis of diethyl alkylsulfanylmethylmalonates from aldehydes, diethyl malonate, and alkylthiols. Graphical Abstract  A synthesis of diethyl alkylsulfanylmethylmalonates catalyzed by KOH in an ionic liquid      

Catalytic oxidation of cyclohexane with hydrogen peroxide and a tetracopper(II) complex in an ionic liquid

The catalytic peroxidative oxidation (with H₂O₂) of cyclohexane in an ionic liquid (IL) using the tetracopper(II) complex [(CuL)₂(μ₄-O,O′,O′′,O′′′-CDC)]₂·2H₂O [HL = 2-(2-pyridylmethyleneamino)benzenesulfonic acid, CDC = cyclohexane-1,4-dicarboxylate] as a catalyst is reported. Significant improvements on the catalytic performance, in terms of product yield (up to 36%), TON (up to 529), reaction time, selectivity towards cyclohexanone and easy recycling (negligible loss in activity after three consecutive runs), are observed using 1-butyl-3-methylimidazolium hexafluorophosphate as the chosen IL instead of a molecular organic solvent including the commonly used acetonitrile. The catalytic behaviors in the IL and in different molecular solvents are discussed.