Vinyl Fluoride Research Articles

Design of fluorinated cyclopropane derivatives of 2-phenylcyclopropylmethylamine leading to identification of a selective serotonin 2C (5-HT2C) receptor agonist without 5-HT2B agonism

A new series of fluorinated 5-HT2C agonists were designed and synthesized on the basis of our previous work on 2-phenylcyclopropylmethylamines as a potential approach for the treatment of central nervous system disorders. Key fluorinated cyclopropane moieties were constructed through transition metal catalyzed [2 + 1]-cycloaddition of aromatic vinyl fluorides, and the absolute stereochemistry of the representative compound (–)-21a was established. Functional activity measuring calcium flux at 5-HT2 receptors reveals high potency for compounds (+)-21a-d. In particular, (+)-21b had no detectable 5-HT2B agonism and displayed reasonable selectivity against 5-HT2A. Molecular docking studies were further performed to explain the compounds’ possible binding poses to the 5-HT2C receptor.

Synthesis and reactivity of phosphine-arenesulfonate palladium(II) alkyl complexes that contain methoxy substituents

Phosphine-arenesulfonate ligands that contain 1-3 methoxy substituents on the benzo linker, P(2-OMe-Ph)2(2-SO3Na-5-OMe-Ph) (Na[1a]), P(2-MeO-Ph)2(2-SO3Na-4,5-(OMe)2-Ph) (Na[1b]) and P(2-MeO-Ph)2(2-SO3Li-3,4,5-(OMe)3-Ph) (Li[1c]) were synthesized and isolated in 52–85% yield. Reaction of Na[1a,b] and Li[1c] with (COD)PdMeCl and pyridine generates the corresponding (PO)PdMe(pyridine) complexes 2a-c. 2a and 2b were isolated in crystalline form in 59% and 86% yield, respectively, while 2c decomposed during attempted isolation. 2a,b polymerize ethylene to linear polyethylene and copolymerize ethylene with vinyl fluoride (VF) to linear copolymer with ca. 0.5 mol % VF incorporation.

Fouling resistant amphiphilic poly(dimethylsiloxane)-linked-poly(ethylene glycol) network on ultrafiltration poly(vinylidene fluoride) membrane and effect of spatial chain arrangement on separation of oil-water emulsions

In continuation of previous work (J. Membr. Sci. 566, 2018, 415) on construction of superhydrophilic membrane with hierarchical surface morphology, herein a facile route for the fabrication of membrane surface containing dangling amphiphilic chains for the separation of oil-in-water emulsions and protein has been reported. A reactive blend membrane prepared with poly(vinyl fluoride), poly(vinyl pyrrolidone) (360 kDa) and a poly(methyl methacrylate)-co-poly(chloromethyl styrene) upon sequential treatment with amine terminated poly(dimethylsiloxane) (H2N-PDMS-NH2) and single-end isocyanate terminated poly(ethylene glycol) (H3CO-PEG-NCO) gave modified membrane containing dangling PDMS-linked-PEG chains. Membrane surface constructed under optimized reaction conditions showed superior fouling resistant ability during separation of oil-in-water emulsions and bovine serum albumin to that of corresponding hydrophilic or hydrophobic membranes. The membrane was able to separate oil-in-water emulsions with oil rejection as high as >99.5%, flux reduction of about 20%, and flux recovery ratio of >98%. The underlying mechanism of good antifouling property of the membrane is attributed to the easy release of fouling agents from the surface by PDMS segments and cleaning by hydrated PEG segments of dangling PDMS-linked-PEG chains. This membrane is stable owing to formation of partially crosslinked network on membrane surface. Evidently, membrane containing both-end tethered PDMS-linked-PEG chains showed comparatively lower antifouling property than that of membrane containing dangling PDMS-linked-PEG chains due to low water response by the PEG chains.

Copper-Catalyzed Regioselective Synthesis of (E)-β-Fluorovinyl Sulfones.

Organofluorine compounds are finding increasing application in a variety of fields such as pharmaceutical, agrochemical, and material sciences. However, given the scarcity of fluorine-containing natural products, advancement in this area depends almost entirely on the development of new synthetic methodologies. In this article, we present the synthesis of a series of previously undescribed (E)-β-fluorovinyl sulfones via a simple copper-catalyzed addition of hydrogen fluoride to alkynyl sulfone starting materials in varying yields and E/Z selectivities. The hydrogenation of these products was also explored and compared with the hydrogenation of the related Z isomers. These new products may find interesting applications, given the versatility of vinyl sulfones in chemical synthesis and the unique properties of vinyl fluorides in biological settings.

Vinyl Fluorides: Competent Olefinic Counterparts in the Intramolecular Pauson-Khand Reaction.

Despite the great advances achieved in the Pauson-Khand reaction and the ever-increasing demand for fluorinated compounds, the use of vinyl fluorides as olefinic counterparts in the above-mentioned transformation had been completely overlooked. Herein, we describe, for the first time, the intramolecular Pauson-Khand reaction of enynes containing a vinyl fluoride moiety.

Transparent Copper-Based Antibacterial Coatings with Enhanced Efficacy against Pseudomonas aeruginosa.

Bacterial surface contamination is a major cause of hospital-associated infections. Antibacterial coatings can play an important role in reducing bacterial transmission via inanimate surfaces in healthcare settings. In this work, transparent copper-based antibacterial coatings were fabricated on commercial poly(vinyl fluoride) and stainless steel. Acrylated quaternized chitosan and ethylenediaminetetraacetic acid were covalently grafted on the substrate for complexation with copper ions. The number of viable Staphylococcus aureus in a droplet [containing ∼104 colony forming units (CFU)], deposited on the copper-containing coating decreased by ∼96% within 60 min at 25 °C. With Pseudomonas aeruginosa, one of the most virulent and hardest to kill bacteria, no CFU could be observed within the same time span (killing efficacy >99.8% based on the detection limit). An increase in copper release from the coating was observed in the presence of P. aeruginosa, which was postulated to be due to the proteolytic activity of P. aeruginosa. The higher efficacy of the coating against P. aeruginosa compared to S. aureus is thus attributed to this increased copper release from the coating, which resulted in extensive bacterial membrane damage and death. The copper-containing coating on poly(vinyl fluoride) retained its antibacterial efficacy after 100 wipes with a water-wetted cloth or isopropanol wipes, demonstrating its durability and long-term efficacy. The coating did not exhibit significant cytotoxicity toward mammalian fibroblasts, further demonstrating its potential for mitigating bacterial transmission in a clinical setting.

Enhanced Output Performance of Nanogenerator Based on Composite of Poly Vinyl Fluoride (PVDF) and Zn:Al Layered-Double Hydroxides (LDHs) Nanosheets

We report a high output performance of flexible nanogenerator (NG) based on the composite of PVDF and Zn:Al layered double hydroxide (LDH) nanosheets. The Zn:Al LDH nanosheets were synthesized via the most facile process by dipping the sputtered Al-doped ZnO (AZO)/Ag/AZO multilayer films into deionized water at room temperature. Here, sputtered AZO/Ag/AZO multilayer was served as a bottom electrode of the energy harvesting device as well as for the growth of Zn:Al LDH nanosheets. The PVDF based NG exhibited an output voltage of ~ 1.71 V and a current density of ~ 0.19 μA cm−2 after poling. While poled-PVDF/Zn:Al LDH composite based NGs exhibited an enhancement in the output performance with an output voltage and current density of ~ 6.24 V and ~ 0.655 μA cm−2, respectively. This simple facile approach can be feasible for the development of large-scale, flexible and an eco-friendly energy harvester that can be widely implemented in self-powered biomedical applications.

Reaction mechanisms and kinetics of the β-elimination processes of compounds CHF2CH2SiFnMe3–n (n = 0–3): DFT and CBS-QB3 methods using Rice-Ramsperger-Kassel-Marcus and transition state theories

The gas-phase β-elimination kinetics of 2,2-difluoroethyltrifluorosilane (1), 2,2-difluoroethylmethyldifluorosilane (2), 2,2-difluoroethyldimethylfluorosilane (3), and 2,2-difluoroethyltrimethylsilane (4) have been investigated computationally using M06-2x exchange-correlation functional as well as the benchmark CBS-QB3 quantum chemical approach. The obtained energy profile has been enhanced with kinetic calculations using statistical Rice-Ramsperger-Kassel-Marcus (RRKM) theory and transition state theory (TST). The calculated results are in good agreement with the available experimental data which obtained by the CBS-QB3 approach. The comparison between all our calculations and experiments indicates that a thermodynamically-controlled reaction that gives more stable products derived from the compound 2 species will be the vinyl fluoride and methyltrifluorosilane species, whereas the elimination of compound 1 into the vinyl fluoride and silicon tetrafluoride species is favorable process from kinetic point of view.In proportion to rather larger barrier heights, pressures where P > 10―4 bar are insufficient to ensure a saturation of the calculated rate constant compared with the RRKM unimolecular rate kinetics (in high-pressure limit).Natural bond orbital analysis revealed that in accordance with an increase of barrier height from compounds 1 to 4, the HOMO-LUMO energy-gaps decreases. Furthermore, the obtained order of barrier heights could be explained by the number of electron-withdrawing fluorine atoms attached to the silicon atom. The occupancies of σC1―F3 bonding orbital for the studied compounds are as follows: 1>2>3>4 and those of σ*C1―F3 antibonding orbital increase in the opposite order (4>3>2>1) by NBO analysis. This fact explains a comparatively easier elimination of the σC1―F3 bond in compound 1 compared to the other compounds. The calculated data reveal that the polarization of the C1―F3 bond in the sense C1δ+–F3δ− is the determining factor in the elimination reaction of the studied compounds.

Diastereo- and Enantioselective Synthesis of Fluorine Motifs with Two Contiguous Stereogenic Centers.

The synthesis of chiral fluorine containing motifs, in particular, chiral fluorine molecules with two contiguous stereogenic centers, has attracted much interest in research due to the limited number of methods available for their preparation. Herein, we report an atom-economical and highly stereoselective synthesis of chiral fluorine molecules with two contiguous stereogenic centers via azabicyclo iridium-oxazoline-phosphine-catalyzed hydrogenation of readily available vinyl fluorides. Various aromatic, aliphatic, and heterocyclic systems with a variety of functional groups were found to be compatible with the reaction and provide the highly desirable product as single diastereomers with excellent enantioselectivities.

Finding the Better Fit: The Microwave Spectrum and Sterically Preferred Structure of trans-1,2-Difluoroethylene-Hydrogen Chloride.

The rotational spectrum of the gas-phase bimolecular heterodimer formed between trans-1,2-difluoroethylene and hydrogen chloride is obtained using Fourier transform microwave spectroscopy from 5.6 to 20.6 GHz. Analysis of the spectrum provides rotational constants and nuclear quadrupole coupling constants that are used to determine the structure of the complex. The HCl molecule forms a hydrogen bond with one of the two electrostatically equivalent fluorine atoms of the difluoroethylene, and this hydrogen bond bends from linearity to allow a secondary interaction between the chlorine atom and the hydrogen atom located cis to the fluorine atom in the hydrogen bond. Because the two hydrogen atoms are likewise electrostatically equivalent, the structure indicates that this is the sterically preferred arrangement in HCl binding to a fluoroethylene rather than the one with the secondary interaction to the geminal hydrogen atom. Detailed comparisons among the geometries of the complexes formed between HCl and HF, on the one hand, and vinyl fluoride, 1,1-difluoroethylene, trans-1,2-difluoroethylene, 1,1,2-trifluoroethylene, and ( E)-1-chloro-2-fluoroethylene, on the other, reveal structural trends accompanying increasing fluorination and substitution of chlorine for fluorine.

Gold-Catalyzed Hydrofluorination of Electron-Deficient Alkynes: Stereoselective Synthesis of β-Fluoro Michael Acceptors.

The gold(I)-catalyzed, stereoselective hydrofluorination of electron-deficient alkynes with triethylamine trihydrogen fluoride (Et3N·3HF) is described. Fluorinated α,β-unsaturated aldehydes, amides, esters, ketones, and nitriles were isolated in moderate to good yields as single diastereomers. In all but four cases, the (Z)-vinyl fluorides were initially formed in ≥97% diastereoselectivity. This work constitutes the first catalytic example of the diastereoselective preparation of a variety of β-alkyl, β-fluoro Michael acceptors from alkynes. Additionally, the described work expands access to β-aryl, β-fluoro Michael acceptors to the synthesis of β-fluoro-α,β-unsaturated amides and nitriles. The monofluoroalkenes formed through this strategy were readily transformed into other fluorine-containing compounds, and the developed method was applied to the synthesis of a fluorinated analogue of Exoderil, a topical antimycotic.

Fluorine‐Containing Functionalized Cyclopentene Scaffolds Through Ring Contraction and Deoxofluorination of Various Substituted Cyclohexenes

The fluorination of some highly‐functionalized cyclopentene derivatives, obtained from various substituted cyclohexenes through a ring‐opening/ring‐contraction procedure, has been investigated. The transformations were found to be highly substrate dependent, and led to the formation of various functionalized alicyclic compounds or heterocycles containing allyl difluoride or vinyl fluoride moieties.

FTIR spectrum of vinyl fluoride near 3.6 μm: rovibrational analysis of the ν4+ν7 band and modelling Coriolis resonances in a seven-level polyad

ABSTRACTThe Fourier transform infrared (FTIR) spectrum of vinyl fluoride, H2C=CHF, has been widely investigated in the region of the ν4+ν7 combination band around 2800 cm−1 at a resolution of 0.005 cm−1. This vibration of A' symmetry gives rise to an a/b-hybrid band with a predominant a-type component. The rovibrational structure is strongly perturbed and the analysis has been rather complicated since this combination band is involved at least in a seven-level interacting polyad, including the ν8+2ν10, 2ν8+ν10, 2ν7+ν9, ν7+ν8+ν12, ν5+ν9+ν10 and ν7+ν10+ν12 vibrational states. The study has been further complicated by the absence of transitions coming from the perturbers that were considered as dark states. The spectral analysis resulted in the identification of 936 transitions with J" ≤ 46 and Ka" ≤ 11, all belonging to the a-type component. Most of the assigned data have been fitted using the Watson's A-reduction Hamiltonian in the Ir representation and proper Coriolis perturbation operators. The model employed includes seven different resonances within a complex polyad resonant system and a set of spectroscopic constants for the ν4+ν7 combination band, for the dark states, and Coriolis coupling coefficients have been determined.

Organoselenium-Catalyzed Oxidative Allylic Fluorination with Electrophilic N–F Reagent

An efficient route of organoselenium-catalyzed oxidative allylic fluorination has been developed. In this transformation, bulky electrophilic fluorinating reagent N-fluoro-2,4,6-trimethylpyridinium triflate (TMFP-OTf) was employed as the oxidant and fluorine source. Notably, TEMPO as an additive affects the fluorination and leads to better substrate scope and excellent functional group tolerance. By this protocol, a variety of allylic fluorides were synthesized in good to excellent yields. The obtained allylic fluorides could be converted into vinyl fluorides efficiently in the presence of an appropriate base.

Transparent Copper-Loaded Chitosan/Silica Antibacterial Coatings with Long-Term Efficacy.

Bacteria-contaminated inanimate surfaces within hospitals and clinics result in transmission of pathogens via direct or indirect contact, leading to increased risk of healthcare-associated infections (HAI). The use of antibacterial coatings is a potential way of reducing the bacterial burden, but many surfaces such as instrument panels and monitors necessitate the coatings to be transparent while being highly antibacterial. In this work, silica nanoparticles (SiO2 NPs) were first grown over a layer of acrylated quaternized chitosan (AQCS) covalently immobilized on commercially available transparent poly(vinyl fluoride) (PVF) films. The SiO2 NPs then served as nanoreservoirs for adsorption of copper ions. The coated PVF films were transparent and reduced viable bacterial count by ∼99% and 100%, when incubated with a bacteria-loaded droplet for 60 and 120 min, respectively. The killing efficacy of these coatings, after wiping 100 times, with a deionized water-wetted cloth was reduced slightly to 97-98%. The stability of these coatings can be further improved with the deposition of another layer of cationic quaternized chitosan (QCS) over the negatively charged SiO2 NP layer, wherein the coatings maintained ∼99% killing efficacy even after 100 wipes. These coatings showed no significant toxicity to mammalian cells and, hence, can potentially be used in a clinical setting for reducing HAI.

Preparation and evaluation of amphiphilic polymer as fouling-release coating in marine environment

Polystyrene–polybutadiene–polystyrene (SBS), vinyl fluoride silicone (BD-FT-LSR) and polyethylene glycol were chosen as the reactors to synthesize amphiphilic polymer which was used to prepare a new type of fouling-release coating. To evaluate the fouling-release performance and explore the mechanism of the coating, artificial and real-sea environment tests were carried out in the experiments, respectively. IR and 1H NMR were utilized to characterize the structure of the polymer. The effect of fouling-release agent was explored by considering changes in the parameters of surface contact angle, XPS, elastic modulus, and TEM. Results of real-sea tests show that the new amphiphilic fouling-release coating has a very good antifouling performance and can be re-cleaned after 6 months of testing in the real-sea environment. These can be explained through hydrophilic PEG migrating to the surface to form a comb-type structure which reduces the adhesion strength of fouling organisms that can then be self-cleaned by flow from the surface of coatings.

Thermodynamic measurement and modeling of vinyl fluoride solubility in aqueous lithium Bis(trifluoromethylsulfonyl)imide Li+Tf2N− + H2O solutions

The solubility of gaseous vinyl fluoride (VF) was measured in lithium bis(trifluoromethylsulfonyl)imide (Li+Tf2N−) + water (H2O) solutions at salt compositions on a solute (VF) free basis of 20.15, 40.0, and 80.0 wt.% at isothermal conditions of approximately 283 K, 304 K, and 372 K using a volumetric view cell. The experimental results demonstrated that vinyl fluoride is highly soluble in aqueous Li+Tf2N− salt solutions and that solubility is directly proportional to salt loading with the greatest VF solubilities (xVF≈0.0629) observed in samples containing 80.0 wt.% Li+Tf2N−. The experimental phase equilibrium results were successfully modeled by a standard Peng-Robinson equation of state which utilized a van der Waals 1-parameter mixing rule and four binary interaction parameters (two temperature dependent and two temperature independent). The absolute average deviation (AAD) in pressure between experimental and regressed data was 1.71% indicating the excellent model fit. The significant thermodynamic vinyl fluoride sorption capacity of Li+Tf2N− + H2O solutions indicate their potential to be utilized as improved solvents for poly(vinyl fluoride) polymerization reactions.

Rotational spectrum and structural analysis of CH⋯F interactions in the vinyl fluoride⋯1,1-difluoroethylene dimer

The structure of the weakly bound dimer of 1,1-difluoroethylene with vinyl fluoride was studied using Fourier-transform microwave spectroscopy in the 6–19GHz range. In the observed dimer structure each monomer acts as both a weak bond donor and acceptor, giving a cyclic arrangement of CH⋯F contacts. The difluoroethylene CC bond is roughly perpendicular to the vinyl fluoride CC bond, forming the cross of a T-shaped carbon atom framework, resembling the lowest energy structure predicted by MP2/6-311++G(2d,2p) calculations. Observed CH⋯F distances are similar to those of vinyl fluoride and 1,1-difluoroethylene complexes with difluoromethane and HCCH. The dipole moment of the dimer was measured using the Stark effect, giving values of μa=0.9003(19) D, μb=0.030(8) D and μtotal=0.9008(22) D. A second ab initio structure, with the CC bonds in a slipped parallel arrangement, was predicted to be about 38cm−1 higher in energy than the T-shaped conformation. This higher energy arrangement has not been observed experimentally..

Olefin Insertion into a Pd-F Bond: Catalyst Reactivation Following β-F Elimination in Ethylene/Vinyl Fluoride Copolymerization.

The discrete (phosphinoarenesulfonate)Pd fluoride complex (POBp,OMe )PdF(lutidine), where POBp,OMe =(2-MeOC6 H4 )(2-{2,6-(MeO)2 C6 H3 }C6 H4 )(2-SO3 -5-MeC6 H3 )P, inserts vinyl fluoride (VF) to form (POBp,OMe )PdCH2 CHF2 (lutidine) and inserts multiple ethylene (E) units to generate polyethylene that contains -CH2 F chain ends. These results provide strong evidence that the -CHF2 and -CH2 F chain ends in E/VF copolymer generated by (phosphinoarenesulfonate)PdR catalysts form by β-F elimination of Pd(β-F-alkyl) species, VF or E insertion of the resulting (PO)PdF species, and subsequent chain growth. These results also imply that β-F elimination is not an important catalyst deactivation reaction in this system.

Olefin Insertion into a Pd–F Bond: Catalyst Reactivation Following β‐F Elimination in Ethylene/Vinyl Fluoride Copolymerization

AbstractThe discrete (phosphinoarenesulfonate)Pd fluoride complex (POBp,OMe)PdF(lutidine), where POBp,OMe=(2‐MeOC6H4)(2‐{2,6‐(MeO)2C6H3}C6H4)(2‐SO3‐5‐MeC6H3)P, inserts vinyl fluoride (VF) to form (POBp,OMe)PdCH2CHF2(lutidine) and inserts multiple ethylene (E) units to generate polyethylene that contains −CH2F chain ends. These results provide strong evidence that the −CHF2 and −CH2F chain ends in E/VF copolymer generated by (phosphinoarenesulfonate)PdR catalysts form by β‐F elimination of Pd(β‐F‐alkyl) species, VF or E insertion of the resulting (PO)PdF species, and subsequent chain growth. These results also imply that β‐F elimination is not an important catalyst deactivation reaction in this system.