The α,α-difluoro-β-hydroxyketone skeleton is an important pharmacodynamic structure in the synthesis study of pharmaceuticals. Herein, we describe a novel iron mediated Reformatsky reaction of iododifluoroacetophenones with aldehydes, which offers a relatively more economical and environment friendly route for the construction of α,α-difluoro-β‑hydroxyl ketone with good yield. In addition, iron shows wider applicability compared with other metals. It can mediate the reaction between iodifluorophenone and α,β-unsaturated ketones or sulfonimides, obtaining 1,2-addition products and α,α-difluoro-β-aminone compounds, respectively.

Abstract not available

Attempts to prepare Cs[MVIF7] and Cs2[MVIF8] salts by photochemical reactions between CsF, noble metal M (M = Ru, Rh, Os, Ir, Pt) and UV-irradiated F2 in anhydrous HF failed. The main products were Cs[MVF6] salts. The formation of MF6 (M = Rh, Os, Ir) was also observed. The reaction between PtF6 and a solution of CsF in anhydrous HF resulted in the formation of CsPtF6 and the release of elemental F2. The crystal structures of the Cs[MVF6] salts (M = Ru, Rh, Os, Ir, Pt) were determined on single crystals. They are isotypic and crystallize in the trigonal space group R ̅3 (No. 148), belonging to the KAsF6 (KOsF6) family of crystal structures. The Raman spectra of Cs[MF6] salts (M = Ru, Rh, Os, Ir, Pt) are also described.

Nuclear magnetic resonance (NMR) is a unique analytical technique because it is capable of providing structural information about molecules at the atomic level. However, the complicated spectral assignments and the inherently low sensitivity without resorting to hyperpolarization methods hamper the widespread applications of NMR techniques in the analysis of complex real-world samples. Through a combination of 19F NMR and ingeniously designed molecular probes, the dynamic recognitions of target analytes can be transduced into easily interpretable 19F NMR signals of characteristic chemical shifts. The method has demonstrated robust performance for the precise multi-component analysis of complex mixtures and the enantiodifferentiation of chiral analytes that are difficult to resolve by chiral chromatographic methods. Here, we highlight a few recently developed 19F-labeled probes and provide discussions on their recognition properties, analyte scopes, and applications under different scenarios.

The preparation of aliphatic SF5-compounds (i.e., RCH2CH2SF5 where R is a functionalized alkyl chain) using a Kolbe-based reaction was explored. In this electrochemical approach, 2-(pentafluoro-λ6-sulfanyl)acetic acid, used as the “SF5CH2” source, is reacted with an aliphatic carboxylic acid. A total of 9 examples of unsymmetrical coupling between 2-(pentafluoro-λ6-sulfanyl)acetic acid and a range of aliphatic carboxylic acid was achieved with NMR yields ranging from 15% to 66% (up to 62% isolated yield). Even if the method leads to modest yields, it represents one of the very few strategies to rapidly access aliphatic SF5-containing compounds.

The ability of binary fluorides (MFx, x = 1 - 7) to donate fluoride ions to the Lewis acids AsF5 and SbF5, i.e., the synthesis and characterization of solids with emphasis on structural data, are comprehensively reviewed herein. If the starting binary fluoride compound MFx does not exist, a different approach must be taken to synthesize the corresponding MFx⋅nPnF6 compound. In addition to the solid compounds isolated in MFx/AsF5 and MFx/SbF5 systems, several other examples are given where Mn+ was detected in HF-AsF5 or HF-SbF5 solutions, but the corresponding salts were never isolated in the condensed state. AsF5 and SbF5 are strong Lewis acids and strong fluoride ion acceptors. In MFx/PnF5 systems (n = 1-7; Pn = As, Sb), AsF5 forms only [AsF6]− salts, whereas reactions with SbF5 give oligomeric [Sb2F11]− or [Sb3F16]− salts in addition to [SbF6]−. Most reactions in MFx/PnF5 systems occurred by direct interaction of the reactants with/without the use of a suitable solvent (anhydrous HF, SO2, etc.). Liquid anhydrous HF (aHF) proved to be the most suitable solvent. When performing reactions with AsF5, even at low concentrations, in aHF, the oxidizing power of AsF5 should be taken into account. SbF5 is completely ionized in HF solutions in the form of [SbF6]−, [Sb2F11]−, [Sb3F16]−, and/or [Sb4F21]−, depending on the concentration. Attempts to grow single crystals MFx⋅nPnF6 from corresponding saturated solutions often resulted in HF-containing [PnF6]− salts. Examples of such compounds are also included in this work. In addition, a brief overview of [PnF6]−, [Pn2F11]− and [Pn3F16]− salts (Pn = As, Sb) with homopolyatomic cations [Mx]n+ is given.

Here, a number of symmetric and unsymmetric N-heterocyclic carbene (NHC) precursors based on benzimidazol-2-ylidene are synthesized. The N-benzyl substituent in these compounds has an electron-withdrawing group (F) at the para position. The structure of these compounds was characterized using elemental analysis and various spectroscopic methods (FTIR and NMR). The molecular and crystal structures of compound 1f and compound 1h were unambiguously elucidated through single-crystal X-ray diffraction analysis. According to the X-ray studies, compound 1f exhibits the formation of a U-shaped molecule whereas compound 1h has a Z-shape formation. In addition, the enzyme inhibition activities of these compounds were investigated against acetylcholinesterase (AChE) and carbonic anhydrases (hCAs). They showed a highly potent inhibition effect on AChE and hCAs (Ki values are in the range of 14.84±1.91 to 174.80±23.60 nM for AChE, 22.41±1.93 to 188.67±27.05 nM for hCA I and 35.29±7.21 to 136.55±17.61 nM for hCA II). These results may contribute to the design and development of new drug candidates, particularly for treatment of some widespread disorders displayed in the world including Alzheimer's disease and glaucoma.

Nucleophilic substitutions of fluorine moieties on fluorographite by hydroxyl groups are carried out by a strategy in which the parallel reductive defluorinations are minimised. Mild sonochemical exfoliation of the resulting product in water provides an aqueous dispersion of hydroxylated fluorographene (HFG) in which C-F bonds are largely semi-ionic in character. Upon subsequent hydrothermal treatment with hydrogen peroxide, additional fluorinations may take place because of adsorbed fluoride ions. Further, oxidative etching results in the formation of blue fluorescent fluorine-rich small sized (1- 2.5 nm) graphene quantum dots (FGQDs) with excellent solubility and high stability. The prepared FGQDs is shown to be a good sensing platform for the detection of Fe3+ions in aqueous solution. A good linear response is obtained for Fe3+ concentrations over a range of 0–90 µM with a limit of detection of 1.93 µM.

Herein, we developed the palladium-catalyzed Sonogashira-type cross-coupling of 1‑bromo-2,2-difluoroethylene with a variety of aromatic and aliphatic terminal alkynes proceeds smoothly at mild reaction condition to access the corresponding gem‑difluoroenyne derivatives. 1-Bromo-2,2-difluoroethylene is a useful difluoroethenyl source because of its commercially available and easy-to-handle. This new synthetic protocol provided a novel strategy to directly construct gem‑difluoroenynes with good functional group tolerance and high yields.

The pyrolysis behaviors of 2,3,3,3-tetrafluroropropene (R1234yf) had been first studied in a flow reactor pyrolysis apparatus coupled with the synchrotron vacuum ultraviolet photoionization mass spectrometry and gas chromatography. The pyrolysis temperature, reaction products and intermediates were measured at atmospheric pressure. The experimental results revealed that the initial pyrolysis temperature of R1234yf was 1040K and the thermal decomposition was accelerated with the increase of temperature. It was found that the pyrolysis reaction of R1234yf will be replaced by a self-polymerization reaction at 1160 K. In order to explore the chemical process of R1234yf pyrolysis, a detailed kinetic simulation was performed and compared with experimental results. The calculated results indicated that the unimolecular decomposition paths took a dominant role in the whole pyrolysis processes. The intermediates of C2H2, C2HF, CF2, CHF3, CF4 and CF3CF3 were detected in the pyrolysis experiments. Moreover, the distribution characteristics and sensitivity analysis of the vital fluorinated species of CF2, C2H2, CF4, CF3CF3 and HF were discussed. All of these founding could provide reliable data for the development of pyrolysis models and guidance for the use of R1234yf in the refrigeration system.

Isatin and substituted isatins were subjected to Aldol condensation with various ketones. The resulted 3-hydroxy compounds were transformed into fluorine derivatives. Thus obtained, 3-fluoro-3-substituted oxindoles were screened for Insilco evaluation against anti-cancer targets VEGFR2 and GSK-3β. The study reveals that the fluoro compounds showed binding at their active sites. Particularly, compounds 4i, 4n and 4q shows the best binding affinity and similar hydrophobic interactions as their respective co-crystallized ligands.

An intramolecular annulation strategy has been developed for the synthesis of fluoroalkylated indane-type analogs. The difluoromethyl and trifluoromethyl functional motifs could be derived from gem-difluoroalkenes through this palladium-catalyzed reaction. This method is also extendable to other fluoroalkenes and multi-component reactions.

A copper-catalyzed three-component radical trifluoromethylalkynylation of unactivated alkenes is realized from Togni-II reagent and readily available terminal alkynes under mild conditions to afford an array of β-trifluoromethylated alkynes. The utilization of a multidentate N,N,N-ligand is crucial for the efficient radical generation and the C(sp3)–C(sp) bond formation. Facile transformations of the difunctionalization products highlight its potential utility in the synthesis of various trifluoromethyl-containing building blocks.

CF3I, as a novel “Halon” replacement fire-extinguishing agent, has the characteristics of low fire-extinguishing concentration, high efficiency, and safety. However, there are still some gaps in its thermal decomposition studies when it is released into the high-temperature fire, so the thermal decomposition of CF3I in oxidizing environments was studied to simulate its diffusive decomposition. The decomposition of CF3I was demonstrated to be accelerated by O2 through experiments in the temperature range of 100°C-800°C in air and N2 atmosphere. The effects of initial concentration, temperature, and residence time on the decomposition rate of CF3I and decomposition characteristics were investigated by tube furnace simulation. The kinetics of thermal decomposition was calculated using the Arrhenius equation in which activation energy Ea is 15.18 kJ/mol and pre-exponential factor (A) is 13.87s−1. Additionally, the thermal decomposition products were examined by GC-MS and FTIR. The experimental results showed that the pyrolysis gas products were mainly CF4, C2F6, and CF2O. Using quantum chemistry and density flooding theory (DFT) calculations, it was concluded that the main decomposition pathway was the reaction of CF3I with singlet oxygen. The reaction pathway of the thermal decomposition of CF3I under a high-temperature fire oxidation environment was proposed based on the products.

A novel synthetic method for the preparation of partially fluorinated unsaturated diethyl phosphonates and phosphonic acids is presented involving the deprotonation of the starting α-hydroxymethyl diethylphosphonate or diethylphosphite with a strong base, followed by in situ addition of an O- or P-nucleophile to the terminal double bond of the perfluorinated olefin. Subsequent elimination of the corresponding leaving groups and restoring of the double bond leads to the target bifunctional perfluorinated olefins. Reaction of the diethyl phosphonate group with trimethylsilyl bromide (TMS-Br) and subsequent hydrolysis/methanolysis gave the corresponding unsaturated phosphonic acids. In the case of using α-hydroxymethyl diethylphosphonate, the reaction may be accompanied by an addition of a second equivalent of an O-nucleophile to form bis-functional internal olefins. The reaction conditions, factors affecting the reactivity, stereo- and regioselectivity of the process, the choice of reagent as well as the course of competitive reactions are discussed, too.

A metal-free protocol for the synthesis of monofluoromethylarenes using diaryliodonium salts and fluorobis(phenylsulfonyl)methane (FBSM) is disclosed. This work represents a facile alternative to traditional metal-mediated monofluoromethylation reactions and utilizes inexpensive and accessible starting materials. The target products can be regioselectively synthesized in excellent yields (up to 97%) and with good functional group tolerance. The thus prepared compounds can be further reduced to furnish monofluoromethylarenes. Our investigations revealed that the counter anion of the iodonium species significantly affects the reaction yield. The ionic nature of the reaction mechanism involving an SNAr type process is elucidated using Hammett's linear free energy analysis, and further supported by control experiments.

In this communication, we present an unusual bifurcated hydrogen bonding array between an OH donor and two C-F bond acceptors. This serendipitously discovered model system was observed in several substrates with various electron demands placed on the OH acceptor, and all show a symmetrical COH—(F-C)2 hydrogen bonding interaction. We employ NMR and IR spectroscopy, X-ray crystallography and DFT theory to characterize this interesting and potentially biochemically relevant hydrogen bonding format.

The abuse of amphetamine (AMPH)-type stimulants (ATS) is a worldwide problem, and there is a need for reliable analytical methods to detect amphetamines and related designer drugs in unknown samples. Nuclear magnetic resonance (NMR) is an indispensable tool for structural elucidation and noninvasive analysis. Herein, we applied recognition-enabled “chromatographic” (REC) 19F NMR for the detection and quantitative analysis of ATS. This method allows for the detection and differentiation of up to 20 ATS and structurally similar analogs in complex mixtures, where the 19F NMR signals are precisely matched with those obtained in the analysis of each component independently. Selecting AMPH as a model analyte, we also illustrate the capability of our approach to quantitatively detect ATS. Further experiments showed that AMPH can be detected at a concentration of 1 μM in artificial urine. These results demonstrate that REC 19F NMR is an efficient and robust strategy for the determination of ATS and related derivatives.

A reagent-free activation method for the addition of SF5Cl on unsaturated compounds was developed using a blacklight compact fluorescent lamp irradiation. A total of 19 examples of alkenes and alkynes were performed, with yields ranging from 25% to 99%. Overall, this method represents an oxygen-free alternative to the most common SF5Cl addition reaction conditions.

All possible fluorine spin-spin coupling constants, 19F‒19F, 19F‒13C, and 19F‒1H, in the series of 12 fluorobenzenes, ranging from fluorobenzene to hexafluorobenzene, were calculated using three different non-empirical formalisms, those based on the DFT, SOPPA, and CCSD formalisms with taking into account solvent, vibrational, and correlation corrections. Within the DFT formalism, three exchange-correlation functionals, namely KT3, M06–2X, and PBE0, were found to be most suitable for the calculation of 19F‒19F, 19F‒13C, and 19F‒1H couplings. Among computational schemes based on the SOPPA and CCSD formalisms, the most efficient and accurate scheme for the calculation of 19F‒13C and 19F‒1H SSCCs is the SOPPA(MP2), while that for the 19F‒19F coupling constants, it is the composite scheme SOPPA(MP2)/CCSD.