Perfluoroalkanesulfonylimides and their lithium salts: synthesis and characterisation of intermediates and target compounds

ECF processes have been extensively experienced and developed since early 1970s at the Fluorine Chemistry Laboratory of Padua University: several classes of perfluorinated inert and functional compounds have been obtained, in particular perfluoro heterocyclics and perfluorinated acid fluorides.Recently the demand for electrolyte salts, applied in lithium batteries, drove our interest to investigate on the perfluoroalkanesulfonylimides.A series of the perfluoroalkanesulfonylfluoride precursors has been obtained by ECF and their metathesis to the related imides and lithium salts has been investigated.A number of representative products has been obtained and characterized in their structure and ionic conductivity.     

Novel and facile synthesis of fluorinated enamino ketones and amino alcohols

Selected imines and one bis-imine react via their enamine tautomers with terminal perfluorinated epoxides, e.g. hexafluoropropene oxide to produce fluorinated enamino ketones or imino ketones. In contrast, internal perfluorinated linear epoxides and one cyclic epoxide yield intermediate imino alcohols, which in one case added hexafluoroacetone, furnishing a new imino diol investigated by X-ray diffraction.     

电化学氟化的新进展

电化学氟化是利用电极反应将氟直接引入有机或无机物的一种重要方法。有机物的电化学氟化方法有两种: 一是Simons于1941年发明的, 用镍作阳极, 在无水氟化氢溶液中, 电解制备全氟化合物的方法。此方法在近年来有不少改进。另一是1970年Rozhkov提出的, 以有机溶剂(如含Et3N.3HF的MeCN)为介质, 在铂阳极上,氧化得到单氟化产物的方法。本文全面地综述了这两种方法, 并着重于最新民发展。     

Electrochemical fluorination of N,N-dimethylperfluoroacylamides

The electrochemical fluorination (ECF) of N,N-dimethylperfluoroacylamides gives the corresponding perfluoro-N,N-dimethylacylamides in low yield. With increase of the number of carbon atoms in the perfluoroacyl radical the yield of the required perfluoro-N,N-dimethylacylamides is slightly increased.     

Imidazopyridine and pyrimidinopyridine systems from perfluorinated pyridine derivatives

Annelation of pentafluoropyridine via an intramolecular nucleophilic aromatic substitution process with benzamidine gave an imidazopyridine system in high yield in a two step process whilst alkyl amidines gave 4-aminotetrafluoropyridine by a competing elimination reaction. 4-Phenylsulfonyl tetrafluoropyridine reacts with amidines to give the corresponding imidazo[4,5-b]pyridine systems. In contrast, 4-cyanotetrafluoropyridine gave a [6,6]-fused pyrimidinopyridine system arising from initial nucleophilic substitution at the C-3 position of the pyridine ring followed by intramolecular cyclization onto the pendant cyano group. The systems prepared by this annelation methodology further demonstrate the utility of perfluorinated heterocyclic substrates for the synthesis of heterocyclic scaffolds that possess multiple functionality and have potential applications in the drug discovery arena.     

Simons electrochemical fluorination of substituted homopiperazines(hexahydro-1,4-diazepines) and piperazines

Simons electrochemical fluorination (ECF) of 1,4-dimethyl-1,4-homopiperazine, methyl 4-ethylhomopiperazin-1-ylacetate and 1,4-bis(methoxycarbonylmethyl)-1,4-homopiperazine was studied. For comparison, ECF of three piperazines with a N-(methoxycarbonylmethyl) group(s) was also studied. ECF of 1,4-dimethyl-1,4-homopiperazine gave a low yield of corresponding perfluoro(1,4-dimethyl-1,4-homopiperazine) together with perfluoro(2,6-diaza-2,6-dimethylheptane) as the major product. Corresponding perfluoro(homopiperazines) with mono- and/or di-(fluorocarbonyldifluoromethyl) groups [CF₂C(O)F] at the 1- and/or 4-position were formed in low yields from methyl 4-ethylhomopiperazin-1-ylacetate and 1,4-bis(methoxycarbonylmethyl)-1,4-homopiperazine, respectively. These new seven-membered perfluoro(1,4-dialkyl-1,4-homopiperazines) were accompanied by the formation of mono- and/or di-basic linear perfluoroacid fluorides resulting from the CC bond scission at the 2- and 3-positions of the ring. From mono- and/or di-N-(methoxycarbonylmethyl)-substituted piperazines, corresponding perfluoropeperazines having the acid fluoride group(s) were formed in low yields.     

The actual state of our knowledge about mechanism of electrochemical fluorination in anhydrous hydrogen fluoride (Simons process)

Based on recent developments the nickel fluorides mediated mechanism of Simons process is proposed. It is shown that the yield of perfluorinated products depends on the nature of the starting material and the peculiarities of the adsorptions processes on the surface of the nickel anode. Some useful empirical rules to optimise the process of electrochemical fluorination in anhydrous hydrogen fluoride are formulated.     

Synthesis and biological evaluation of 99mTc-ECF: a new ethionamide derivative for tuberculosis diagnosis

In this work we propose a technetium-99m-labeled derivative from Ethionamide (ETH), further referred to as ^99mTc-ECF for tuberculosis diagnosis. The biological features of this radioactive agent have been studied. The 2-ethylpyridine-4-carbothioamide-ferrocène (ECF) was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that ^99mTc-ECF is obtained with high radiolabelling yield (>90 %). Radiochemical analysis of ^99mTc-ECF revealed that the molecule was efficiently labeled with a little free remaining pertechnetate. Only 1–2 % of the tracer was leached out from the complex at 24 h when incubated in serum at 37 °C which confirmed its high stability. The sensitivity test of ECF showed that the group of grafted ferrocenyl does not seem to have largely altered the active site of the molecule. In-vitro investigations were conducted using BCG (Bacille Calmette-Guérin) as analogue of Mycobacterium Tuberculosis and Listeria Monocytogenes as negative control. It was proved that for BCG, ECF has kept the bacteriostatic properties of the parent compound (ETH). In physiological conditions, the measured up-take of the tracer with live bacteria was about 24.1 and 7.1 % for BCG and Listeria Monocytogenese, respectively. The comparison of the ^99mTc-ECF accumulation at sites of BCG infected animals, which is expressed as target-to-non-target ratio (found to be equal to 2.15) with other radiotracers was discussed. This allowed us to consider that ^99mTc-ECF could be a reasonable radiotracer for mycobacterial infections. Obtained results were good and encourage to undergo a similar labeling for the Mycobacterium tuberculosis as perspective of this work.     

Porous alumina-based fluorous liquid membranes: Dependence of transport on fluorous solvent

We report here the properties of supported fluorous liquid membranes based on porous alumina. The alumina is first rendered compatible with fluorous solvents by surface modification with an oligomeric perfluoropropylene oxide-based carboxylic acid, Krytox 157FSH. After modification, simply dipping the porous alumina membrane into a perfluorinated solvent results in a supported liquid membrane with high selectivity for fluorous compounds. Two homologous series of compounds differing in the number of -CF₂- groups were investigated, namely esters of cinnamyl alcohol and the analogous naphthyl derivative with 2H,2H,3H,3H-perfluoroalkanoic acids (HOOC-(CH₂)₂-(CF₂)_m−1CF₃, m = 2, 4, 6 and 8). Four perfluorinated membrane solvents (FC-77, PF-5080, FC-3283 and FC-43) were investigated. In FC-3283, the permeabilities, which are the products of a diffusion coefficient and a partition coefficient in the solution-diffusion model, of cinnamyl alcohol derivatives are 3.62 ± 0.36 times greater than those of the analogous naphthyl compounds for the solutes containing the same perfluorinated chain. Permeability, P, increases as the perfluorinated chain length increases in all of the perfluorinated solvents. Values of log(P) vs m are linear with a slope of 0.147 ± 0.002 but with different intercepts for the various solvents. Independent measurements of the partition coefficients of the solutes between the source/receiving phase solvent, ethanol, and the fluorous solvents reveal that the selectivity behavior is dominated by partitioning rather than diffusion. The free energy of transfer of a -CF₂- group (ethanol to perfluorinated solvents) is −1.1 kJ/mol. Despite the fact that the solvents are mixtures, not pure liquids, the partition coefficients are well correlated with values calculated based on group contributions with ‘mobile order and disorder’ theory. The diffusion coefficients of four solutes in four membrane solvents were also determined based on the solution-diffusion model. The Stoke-Einstein equation shows satisfactory estimation of experimental results.     

Radiation-induced grafting of perfluorinated vinyl ether into fluorinated polymer films

We report herein the first successful grafting of perfluorinated vinyl ether monomer into base polymer films by simultaneous radiation method. 2-Bromotetrafluoroethyl trifluorovinyl ether (BrTFF) could be grafted into poly(ethylene-co-tetrafluoroethylene) (ETFE) films by γ-rays irradiation at room temperature. The grafting yield increased linearly with an increase in the dose up to 1400 kGy. The required dose for a satisfactory grafting yield, such as 20%, was as high as ca. 400 kGy probably due to low polymerization reactivity of fluorinated monomers. However, the solvent and catalyst had no positive influence for improving the grafting yield. FTIR spectra and SEM-EDS testified that BrTFF was successfully grafted into ETFE films homogeneously in the perpendicular direction. The thermal analysis of the grafted films further indicated no phase separation between poly(BrTFF) grafts and ETFE films, probably owing to high compatibility of the fluorinated grafts and base polymers.     

An entirely new methodology for synthesizing perfluorinated compounds: synthesis of perfluoroalkanesulfonyl fluorides from non-fluorinated compounds

A new synthetic procedure for the preparation of perfluoroalkanesulfonyl fluorides utilizing liquid-phase direct fluorination with elemental fluorine has been developed. Direct fluorination of a partially fluorinated ester, which has alkanesulfonyl fluoride in the end, was synthesized from non-fluorinated counterparts and perfluorinated acid fluoride according to the PERFECT process, gave the desired perfluorinated product in moderate yield as well as by-products arising from CS bond cleavage. The results of the direct fluorination of some model substrates suggest that the CS bond cleavage occurred due to radical formation at the α-position rather than the β-position.     

The radiation degradation of polytetrafluoroethylene resulting in low-molecular and functionalized perfluorinated compounds

The degradation of polytetrafluoroethylene (PTFE) by high energy radiation with a high dose and in presence of oxygen forms perfluorinated carboxylic acids, among other compounds. In an inert atmosphere (in nitrogen) mixtures of perfluorinated olefines and paraffins of different chain length ranges are obtained. This process represents a new alternative of the synthesis of special active components, such as fluorocarbon surfactants, fluorine containing textile finishing agents, special dielectrics and others. Irradiation of the resulting perfluorinated paraffins (in nitrogen) and of gaseous degradation products of PTFE leads to a significant increase in the yield of perfluorinated olefines. Reaction mechanisms are discussed. Recombinations of radicals obtained by irradiation form branched molecules. The reactions are diffusion controlled. Irradiation of high molecular PTFE leads to low branching. The degree of branching of molecules increases in correlation with a decrease of viscosity of the reaction medium. An apparatus conception pertaining to the process of a continuous degradation of PTFE to perfluoroolefines and perfluoroparaffins in the favourable chain length ranges from six to 14 carbon atoms, according to application, is described. An essential component of this conception is the use of a target which consists of a tempered thin layer which is moved into an inertly processed reactor for irradiation. The action of high energy radiation of relatively low dose in air in presence of reactive substances leads to a finely grained PTFE powder with functional groups, which can be mixed easily with liquids, solutions and polymers.     

Free radical and isomerisation processes during the electrochemical fluorination of n-butyryl chloride, i-butyryl chloride and pivaloyl chloride in anhydrous hydrogen fluoride

Electrochemical perfluorination (ECPF) of the title compounds containing primary, secondary and tertiary carbon atoms was carried out in anhydrous hydrofluoric acid (AHF). Detailed analysis of major and minor products suggest that carbon chain isomerisation involving cyclo-propane intermediate is more prevalent during ECPF of i-butyryl chloride when compared to n-butyryl chloride. Simple statistical probability involving free radical intermediates also support this observation. ECPF involving cyclo-propane intermediate is even more prevalent in pivaloyl chloride containing three methyl substituents. In this case, perfluorinated cyclo-propane intermediates were also observed in the product sample. Distribution of minor perfluorinated and partially fluorinated products also suggest the predominant role of normal free radical pathway involving single-electron transfer.     

Perfluorinated ion exchange polymers and their use in research and industry

Tetrafluoroethylene is copolymerized with a perfluorovinyl ether, containing a functional end group (-SO₂F or -CO₂CH₃) to yield a melt fabricable precursor polymer. After fabrication into the desired shape, the polymer is treated with a solution of potassium hydroxide to convert the functional group to an ion exchange site. The fundamental incompatibility of the ionic group with the perfluorinated polymer backbone results in a unique morphology, particularly in the presence of water or polar organic solvents. This has been the subject of extensive investigations by various research institutions. The most important industrial use for these polymers is in the electrolysis of sodium chloride solutions. Initially introduced in order to eliminate the environmental problems of the amalgam process, their performance has now improved to the point where they offer substantial savings, particularly in terms of energy costs, over the two older processes. An emerging, potentially very important use for perfluorinated ion exchange polymers is as an ionic conductor in fuel cells. Recent advances in this area will be discussed.     

Photodissociation of alkyl bromides

The branching ratios for the production of Br(4²P_{$\text{1}\text{2}$}) following the broadband flash photolysis of the alkyl bromides, CH₃Br and C₂H₅Br, and the perfluorinated molecules, CF₃Br, C₂F₅ Br and n-C₃F₇ Br, have been determined using time-resolved atomic absorption spectroscopy. The production of electronically excited bromine atoms is shown to be inefficient in the case of the alkyl bromides while the perfluorinated molecules yield decreasing amounts of Br(4²P_{$\text{1}\text{2}$}) as the molecular complexity increases, i.e., CF₃Br > C₂F₅Br > C₃F₅Br > C₃F₇. It is also shown that the hydrogenated bromides deactive electronically excited atoms almost two orders of magnitude faster than do the perfluorinated bromides.     

Perfluorinated and partially fluorinated organic compounds. Preparation,characterization and application

Electrochemical fluorination (ECF) of various heterocyclic compounds has been investigated. α,ω-Dimorpholinoalkanes of different chain length (n = 1-6) and of morpholinocyclohexene gave the perfluoro derivatives in yields up to 45%. The crystal and molecular structures of the perfluorinated compounds are presented. The mechanism of ECF for these compounds is discussed on the basis of a steric model. Perfluorocarbon emulsions of second generation were prepared by means of F-dimorpholines and F-cyclohexylmorpholine, acting both as oxygen carriers and as interfacial active compounds (IFACs). The stabilizing effect of these IFACs is interpreted. Semifluorinated alkanes, R_fR_h, are chemically inert and non-toxic. They are useful for blood substitutes in two ways: as co-surfactants to stabilize emulsions with perfluorocarbons and as oxygen carriers instead of perfluorocarbons. The high density of perfluorocarbons cause problems in some field of application in medicine. Therefore symmetrical diethers of the type R_F(CH₂)_mO(CH₂)_nO(CH₂)_mR_F were synthesized. These are inert and biocompatible compounds. Diethers with long R_F-tail and long hydrocarbon spacer are ideal solubilizers for perfluorocarbons with hydrocarbons and vice versa. The diethers with short hydrocarbon spacer and long R_F-tail can be applied in biological systems, because they are not soluble in lipid tissues. Perfluorocarbons (e. g. F-decalin, F-octane) are used as medical tools in ophthalmology, their purity is essential. Not totally fluorinated compounds (1 H-perfluoroalkanes, α,ω-dihydrogenoperfluoroalkanes) are characterized and discussed. 1H-perfluoroalkane is also formed by nucleophilic attack on perfluoroalkyl halide.     

Combining Theory and Experiment to Characterize the Voltammetric Behavior of Nickel Anodes in the Simons Process

The Simons process, otherwise known as the electrochemical fluorination (ECF) method, is widely used in industry to electrolytically synthesize chemicals for various purposes. Even to this day, the exact mechanism of the ECF reaction remains unknown, but is believed to involve the formation of an anodic nickel fluoride film with highly oxidized nickel centers. In this study, experiments and density functional theory calculations are combined to characterize the initial anodic peak occurring at potentials typically required in an ECF cell. NiF₂ is believed to form a passivating layer at low potentials. The calculations show that a potential of +3.1 V is required to oxidize surface Ni²⁺ centers to Ni³⁺. This is in good agreement with the measured anodic peak at +3.57 V.     

A Voltammetric Study of the Kolbe Synthesis with Perfluorinated Oxa Acids: Influence of the Structure of the Fluorocarbon Residue

The Kolbe synthesis with two perfluorinated oxa acids, perfluoro-3,7-dioxa-2-methyloctanoic and perfluorotetrahydro-α-furylacetic, was studied voltammetrically on platinum and glassy carbon anodes in water-acetonitrile and methanol-acetonitrile solutions. The influence exerted on the process by the acid concentration, degree of its neutralization, and solvent was studied. The solvent-anode system exerts a differentiating effect on the reactivity of perfluorinated acids under the conditions of the Kolbe synthesis.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 5, 2005, pp. 762–767.Original Russian Text Copyright © 2005 by Chechina, Tomilov, Sokolov.     

Two procedures for the syntheses of labeled sialic acids and their 1,7-lactones

The synthesis of four deuterated sialic acids and their 1,7-lactones has been performed in two ways, one based on sialic acid classical chemistry, and the other involving a direct exchange of the unlabeled acyl group of N-acetylneuraminic acid with a labeled one mediated by a perfluorinated amide. The final lactonization is promoted by benzyloxycarbonyl chloride.