Multiple Fluorine Atoms Research Articles

Hypervalent iodine catalysis enabled iterative multi-fluorination: not just a simple alternative for the electrochemical approach.

Unlike the well-established fluoroalkylation, the direct incorporation of multiple fluorine atoms into small molecules via iterative fluorinations has been much less investigated. Herein, we report a hypervalent iodine catalytically selective multi-fluorination in which the fluorination degree is controlled by the delicate balance between the HF/amine ratios. The pros and cons of hypervalent iodine catalysis and the previously established electrochemical approach in the iterative multi-fluorinations are also provided.

Collective Effects of Multiple Fluorine Atoms Causing π-philic Characteristic within a Caged Polyoxometalate Framework.

Perfluorination brings about distinctive properties arising from the unusual nature of the F element, which have been extensively developed in materials science and chemistry. Herein we report that the construction of F-rich inner space within a hollowed Mo132 O372 cage ([Mo132 O372 (OCOR)30 (H2 O)72 ]42- ) leads to the emergence of unique guest binding activities in encapsulation. Prominently, the trifluoroacetate-modified cage (R=CF3 , 2) having as many as 90 F groups inside favors trapping cyclopentadiene (Cp), which is hardly trapped by the non-fluorinated counterpart (R=CH3 , 1). Systematic studies using related hydrocarbons show that the amount of the encapsulated guest is correlated with the unsaturation degree of the guests, implying the involvement of the attractive interaction of the CF3 -modified interior wall with the guest π-electron clouds. Control experiments using the semi-fluorinated analogues (R=CF2 H, CFH2 ) reveal that the perfluorination is a critical factor to facilitate the Cp encapsulation by 2, indicating that collective effects of polar C-F bonds spreading over the interior surface, rather than the polarity of the individual C-F bonds, are responsible. We also provide a successful example of the physical molecular confinement within the cage through the "ship-in-a-bottle" Diels-Alder reaction between trapped diene and dienophile.

Efficient chemical synthesis of new thermoplastic fluorinated aromatic polyester

Recently, great interest has been in synthesizing polymers containing fluorine atoms. Fluorinated polymers exhibit high hydrophobicity, low surface energy, good thermal stability, excellent dielectric properties, low water absorption, and good chemical resistance. This work illustrates the synthesis, characterization, and properties of a new fluorinated aromatic polyester. Poly(fluoromandelic acid) (PFMA). PFMA is a new polymer with multiple fluorine atoms on the polymer chain. Simple heating of 4-fluoromandelic acid, without a solvent or a catalyst, under controlled conditions leads to poly(fluoromandelic acid). The reaction runs in the solid state by the elimination of water. The structure of the resulting poly(fluoromandelic acid) consists mainly of a polyester backbone decorated with p-fluorophenyl groups and has carboxyl and hydroxyl groups at the ends of the polymer chain. Mass spectrometry, solid-state 13C nuclear magnetic resonance (13C ss-NMR), liquid NMR, Fourier-transform infrared spectroscopy (FTIR), and Raman spectroscopy elucidated the polymer chain structure. The thermal stability of the polymer was also studied, and the melting point was determined from the differential scanning calorimetry. In the case of poly(fluoromandelic acid), the thermal conductivities and diffusivity were measured by the transient plane source (TPS) technique, also referred to as the Hot Disk method. The thermal conductivity measured at different temperatures will also be discussed in relation to the structure of the analyzed polymer as correlated with the crystallinity of the polymer structure determined by XRD diffraction. It was also shown that the new fluorinated aromatic polyester exhibited remarkable hydrophobicity.

Electron in a cube: Synthesis and characterization of perfluorocubane as an electron acceptor.

Fluorinated analogs of polyhedral hydrocarbons have been predicted to localize an electron within their cages upon reduction. Here, we report the synthesis and characterization of perfluorocubane, a stable polyhedral fluorocarbon. The key to the successful synthesis was the efficient introduction of multiple fluorine atoms to cubane by liquid-phase reaction with fluorine gas. The solid-state structure of perfluorocubane was confirmed using x-ray crystallography, and its electron-accepting character was corroborated electrochemically and spectroscopically. The radical anion of perfluorocubane was examined by matrix-isolation electron spin resonance spectroscopy, which revealed that the unpaired electron accepted by perfluorocubane is located predominantly inside the cage.

(Invited) Synthesis and Properties of Fluorinated Cubanes

Electron acceptor molecules play an important role in the design of organic functional materials. The electron acceptor molecules reported so far are limited to π-conjugated molecules, which stabilize the accepted electrons by delocalizing them in the extended π-orbitals. In contrast, in perfluorocubane, in which eight carbons of the box-shaped molecule are fluorinated, the eight σ* orbitals of the C-F bonds overlap inside the box and are expected to accept and stabilize electrons there.[1] Since perfluorocubane is expected to accept electrons by overlapping σ* orbitals, it will probably show different physical properties from those of π-conjugated electron acceptor molecules.In the present study, we have succeeded in introducing multiple fluorine atoms into the carbon of cubane derivatives by using an original synthetic technique using fluorine gas,[2] which cannot be used in conventional synthetic organic chemistry. Using this key reaction, perfluorocubane (1), heptafluorocubane (2), and hexafluorocubane (3) were synthesized. Electrochemical and spectroscopic measurements demonstrated that the electron affinity increased with increasing the number of fluorine atoms. Furthermore, the successful observation of perfluorocubane radical anion by ESR measurement will be reported.[1] Irikura, K. K. J. Phys. Chem. A 2008, 112, 983–988. [2] Okazoe, T. J. Fluorine Chem. 2015, 174, 120–131. Figure 1

Dual Triplet Sensitization Strategy for Efficient and Stable Triplet–Triplet Annihilation Upconversion Perovskite Solar Cells

Dual Triplet Sensitization Strategy for Efficient and Stable Triplet–Triplet Annihilation Upconversion Perovskite Solar Cells

Recent Advances in Photoinduced Perfluoroalkylation Using Perfluoroalkyl Halides as the Radical Precursors

AbstractPerfluoroalkylation is one of the most important methods for the introduction of multiple fluorine atoms into organic molecules in a single step. The use of photoinduced technology is a common strategy that uses the outstanding oxidation or reduction ability of a photo­redox catalyst in its excited state to generate perfluoroalkyl radicals from perfluoroalkyl halides. The perfluoroalkyl radicals thus obtained can undergo various subsequent reactions under mild conditions, such as ATRA reaction of alkenes, alkynes, and 1,n-enynes; carbo/heteroperfluoroalkylation of alkenes and isocyanides; and C–H/F perfluoroalkyl­ation. This allows the expedient incorporation of various perfluoroalkyl groups into the molecular motifs. Perfluorinated functional groups are still in demand in pharmaceutical and material sciences; this short review discusses recent advances in photoinduced perfluoroalkylation methodologies and technologies.1 Introduction2 Photocatalytic Perfluoroalkylation of Alkenes, Alkynes, and 1,n- Enynes3 Photocatalytic Carboperfluoroalkylation or Heteroperfluoro­alkylation of Alkenes, Alkynes, Isocyanides, and Hydrazones4 Photocatalytic ATRE Reactions of Alkenes with Perfluoroalkyl Halides­5 Photocatalytic C–X (X = H, F) Bond Perfluoroalkylation6 Continuous Flow Strategies in Photocatalytic Perfluoroalkylation7 Conclusions

Roll-to-roll compatible quinoxaline-based polymers toward high performance polymer solar cells

In this article, two D–A-type quinoxaline-based polymers with multiple fluorine atoms, denoted by PB-QxF and PBF-QxF, were synthesized and tested for polymer solar cells (PSCs).

Synthesis and applications of theranostic oligonucleotides carrying multiple fluorine atoms.

The use of various oligonucleotide (ON) syntheses and post-synthetic strategies for targeted chemical modification enables improving their efficacy as potent modulators of gene expression levels in eukaryotic cells. However, the search still continues for new approaches designed for increasing internalization, lysosomal escape, and tissue specific delivery of ON. In this review we emphasized all aspects related to the synthesis and properties of ON derivatives carrying multifluorinated (MF) groups. These MF groups have unique physico-chemical properties because of their simultaneous hydrophobicity and lipophobicity. Such unusual combination of properties results in the overall modification of ON mode of interaction with the cells and making multi-fluorination highly relevant to the goal of improving potency of ON as components of new therapies. The accumulated evidence so far is pointing to high potential of ON probes, RNAi components and ON imaging beacons carrying single or multiple MF groups for improving the stability, specificity of interaction with biological targets and delivery of ONs in vitro and potentially in vivo.

Syntheses of Atypically Fluorinated Peptidyl Macrocycles through Sequential Vinylic Substitutions.

Small peptides containing combinations of cysteine, tyrosine, histidine, and serine residues react with octafluorocyclopentene (OFCP) to afford atypically structured macrocycles through successive vinylic substitutions. The reactions proceed rapidly in air at 0 °C and are tolerant of spectating tryptophan, asparagine, glutamine, and threonine residues. Hexapeptides of consensus sequence YXCXXC displace four fluorine atoms from OFCP to generate fluorinated macrobicyclic compounds that display dual-turn surfaces. The method provides facile access to a wide range of previously unknown heterocyclic structures.

A highly selective dispersive liquid–liquid microextraction approach based on the unique fluorous affinity for the extraction and detection of per- and polyfluoroalkyl substances coupled with high performance liquid chromatography tandem–mass spectrometry

In the present study, a highly selective fluorous affinity-based dispersive liquid–liquid microextraction (DLLME) technique was developed for the extraction and analysis of per- and polyfluoroalkyl substances (PFASs) followed by high performance liquid chromatography tandem–mass spectrometry. Perfluoro-tert-butanol with multiple C-F bonds was chosen as the extraction solvent, which was injected into the aqueous samples with a dispersive solvent (acetonitrile) in a 120:800 (μL, v/v) mixture for PFASs enrichment. The fluorous affinity-based extraction mechanism was confirmed by the significantly higher extraction recoveries for PFASs containing multiple fluorine atoms than those for compounds with fewer or no fluorine atoms. The extraction recoveries of medium and long-chain PFASs (CF2 > 5) exceeded 70%, except perfluoroheptanoic acid, while those of short-chain PFASs were lower than 50%, implying that the proposed DLLME may not be suitable for their extraction due to weak fluorous affinity. This highly fluoroselective DLLME technique can greatly decrease the matrix effect that occurs in mass spectrometry detection when applied to the analysis of urine samples. Under the optimum conditions, the relative recoveries of PFASs with CF2 > 5 ranged from 80.6-121.4% for tap water, river water and urine samples spiked with concentrations of 10, 50 and 100 ng/L. The method limits of quantification for PFASs in water and urine samples were in the range of 0.6–8.7 ng/L. Furthermore, comparable concentrations of PFASs were obtained via DLLME and solid-phase extraction, confirming that the developed DLLME technique is a promising method for the extraction of PFASs in real samples.

Quantitative characterization of new supramolecular synthons involving fluorine atoms in the crystal structures of di- and tetrafluorinated benzamides.

Strong hydrogen bonds play a significant role in crystal packing. In particular, the involvement of interactions involving fluorine in controlling the crystal packing requires appropriate attention, especially in the presence of other strong hydrogen bonds. In the present study, a detailed quantitative assessment has been performed of the nature, energetics and topological properties derived from the electron density in model compounds based on fluorinated benzamides (a total of 46 fluorine-substituted benzamides containing multiple fluorine atoms) in the solid state. The primary motivation in the design of such molecules is to enhance the acidity of the interacting H atoms in the presence of an increasing number of F atoms on the molecular scaffold, resulting in increased propensity towards the formation of intermolecular interactions involving organic fluorine. This exercise has resulted in the identification of new and frequently occurring supramolecular synthons involving F atoms in the packing of molecules in the solid state. The energetics associated with short and directional intermolecular Csp2-H...F-Csp2 interactions with significantly high electrostatic contributions is noteworthy, and the topological analysis reveals the bonding character of these ubiquitous interactions in crystal packing in addition to the presence of Csp2-F...F-Csp2 contacts.

Hexaphyrin as a Potential Theranostic Dye for Photothermal Therapy and 19 F Magnetic Resonance Imaging.

Two features of meso-Aryl-substituted expanded porphyrins suggest suitability as theranostic agents. They have excellent absorption in near infrared (NIR) region, and they offer the possibility of introduction of multiple fluorine atoms at structurally equivalent positions. Here, hexaphyrin (hexa) was synthesized from 2,6-bis(trifluoromethyl)-4-formyl benzoate and pyrrole and evaluated as a novel expanded porphyrin with the above features. Under NIR illumination hexa showed intense photothermal and weak photodynamic effects, which were most likely due to its low excited states, close to singlet oxygen. The sustained photothermal effect caused ablation of cancer cells more effectively than the photodynamic effect of indocyanine green (a clinical dye). In addition, hexa showed potential for use in the visualization of tumors by 19 F magnetic resonance imaging (MRI), because of the multiple fluorine atoms. Our results strongly support the utility of expanded porphyrins as theranostic agents in both photothermal therapy and 19 F MRI.

Novel Ir(ppy)3 Derivatives: Simple Structure Modification Toward Nearly 30% External Quantum Efficiency in Phosphorescent Organic Light‐Emitting Diodes

Novel tris-cyclometalated iridium phosphors with diphenylamino groups and multiple fluorine atoms incorporated on cyclometalating ligands are developed for use as doped emitters in organic light-emitting diodes (OLEDs). The green phosphorescent OLEDs based on heteroleptic iridium complexes exhibit an external quantum efficiency of 30% even using simple device structures, which is among the highest values ever reported for iridium phosphors. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Synthesis and Properties of Dendritic Emitters with a Fluorinated Starburst Oxadiazole Core and Twisted Carbazole Dendrons

Three generations of novel dendrimers (G1, G2, and G3) with an electron-deficient fluorinated starburst oxadiazole core and twisted carbazoles as dendrons were synthesized via aromatic nucleophilic substitution reaction at ambient temperature by the weak base potassium fluoride with a high selectivity in a nearly quantitative yield, which was attributed to the high reactivity of the para fluorine atom activated by oxadiazole and multiple fluorine atoms. 1H NMR, 19F NMR, elemental analysis, and MALDI-TOF MS results confirmed the designed chemical structures. Varying the generation to gradually modify the dendrons could gradiently modulate the HOMO−LUMO energy band gaps of Gn, which was verified by cyclic voltammetry results. Photoluminescent spectra showed the dual fluorescence emission of the dendrimers in solutions, which indicated that twist intramolecular charge transfer occurred between oxadiazole and carbazole separated by nonconjugated bonds. The Gn-based devices with the configuration of ITO/PEDOT:PSS/Gn/TPBI/AlQ/LiF/Al displayed a stable green emission in their electroluminescent spectra with a gradual increase in external quantum efficiency and current efficiency for higher-generation dendrimers, owing to gradually improved charge transport. The device with G3 possessed the lowest turn-on voltage along with the highest external quantum efficiency of 1.49%, maximum current efficiency of 4.6 cd/A, and a high luminance of 4882 cd/m2, indicating that it had the best carrier balance.

Substituted piperazines as novel dipeptidyl peptidase IV inhibitors

Incorporation of a fluorophenyl β-amino amide moiety into piperazine screening lead 2 has resulted in the discovery of a structurally novel series of potent and selective DP-IV inhibitors. Simplification of the molecule and incorporation of multiple fluorine atoms on the phenyl ring has provided low molecular weight analogs such as compound 32, which is a 19 nM DP-IV inhibitor with >4000-fold selectivity over QPP.

Surface Structure of A Liquid Perfluoropolyether Examined by Reactive Ion/Surface Scattering

ABSTRACTThis study shows that reactive ion/surface collisions can provide information on the surface structure of molecular systems. The microscopic structures of perfluorinated polyether (PFPE) liquid surfaces are characterized by ion/surface collision experiments in a mass spectrometer and the results are compared to those obtained with a fluorinated self-assembled monolayer (F-SAM) surface. Low energy (< 100 eV) beams of W+ and W(CO)6+ ions are used for surface-induced dissociation (SID) and ion/surface reactive scattering, while Xe+ and Kr+ beams are used for chemical sputtering experiments. Both the PFPE and F-SAM surfaces show similar SID fragments while reactions with W+ and W(CO)6+ lead to the scattered metal ion with multiple fluorine atoms attached. The main peaks in chemical sputtering spectra are similar for both surfaces as well. Both hydrogen probe beams and chemical sputtering confirm that the liquid PFPE surface is nearly free of impurities. Our results on both surfaces also suggest that the CF3 group of the monomer units is most likely projected outward from the bulk of the liquid surface.