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Two series of novel fluorinated Tubastatin A derivatives based on cyclopentane or cyclohexane substitution were first time synthesized by 5 steps at high yield. The influence of the cycloalkanes substituted N‐methylpiperidine and/or fluorinated group on the cap group of Tubastatin A for the in vitro anti‐tumor activity of seven different tumor cell lines (human hepatoma cells Bel7402 and HepG2, human nasopharyngeal carcinoma cells CNE2 and SUNE1, human breast cancer cells MDA‐MB‐231 and MCF‐7, and human pancreatic cancer cells SW1990) was investigated. Compared with Tubastatin A, these novel derivatives with fluorinated groups on the benzene ring of the cap group enhance activity, and modification of the N‐methylpiperidine to cycloalkanes of the cap group improves solubility. The most promising compound trifluoromethyl and cyclohexane substituted derivative, N‐hydroxy‐4‐((6‐(trifluoromethyl)‐1,2,3,4‐tetrahydro‐9H‐carbazol‐9‐yl)methyl) benza‐mide (6 h), had a wide range of anti‐tumor cell range, the IC50 value for human pancreatic cancer cell line SW1990 was 1.17 μM. Hence, fluorinated groups and cyclohexane result in a wide range of anti‐tumor cell range and good anti‐cancer activity. [ABSTRACT FROM AUTHOR]

Trifluoromethyl heterocyclic compounds have high lipophilicity, metabolic stability and binding selectivity, so it is very important to develop their synthetic methods. This review provides an overview of synthesis of trifluoromethyl substituted heterocyclic compounds from β-trifluoromethylated acrylates over the period from 2018 to the present. [ABSTRACT FROM AUTHOR]

All areas of the modern society are affected by fluorine chemistry. In particular, fluorine plays an important role in medical, pharmaceutical and agrochemical sciences. Amongst various fluoro-organic compounds, trifluoromethyl (CF3) group is valuable in applications such as pharmaceuticals, agrochemicals and industrial chemicals. In the present study, following the strict OECD modelling principles, a quantitative structure–toxicity relationship (QSTR) modelling for the rat acute oral toxicity of trifluoromethyl compounds (TFMs) was established by genetic algorithm-multiple linear regression (GA-MLR) approach. All developed models were evaluated by various state-of-the-art validation metrics and the OECD principles. The best QSTR model included nine easily interpretable 2D molecular descriptors with clear physical and chemical significance. The mechanistic interpretation showed that the atom-type electro-topological state indices, molecular connectivity, ionization potential, lipophilicity and some autocorrelation coefficients are the main factors contributing to the acute oral toxicity of TFMs against rats. To validate that the selected 2D descriptors can effectively characterize the toxicity, we performed the chemical read-across analysis. We also compared the best QSTR model with public OPERA tool to demonstrate the reliability of the predictions. To further improve the prediction range of the QSTR model, we performed the consensus modelling. Finally, the optimum QSTR model was utilized to predict a true external set containing many untested/unknown TFMs for the first time. Overall, the developed model contributes to a more comprehensive safety assessment approach for novel CF3-containing pharmaceuticals or chemicals, reducing unnecessary chemical synthesis whilst saving the development cost of new drugs. [ABSTRACT FROM AUTHOR]

Anovel series of C-, N-, and F-doped TiO2 photocatalysts were fabricated using a simple sol-gel method, utilizing 4-(trifluoromethyl)nicotinic acid (TFNA) as a precursor for carbon, nitrogen, and fluorine doping. The resulting materials were characterized using different advanced techniques such as X-ray Diffraction (XRD), Diffuse Reflectance Spectroscopy (DRS), Raman spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), and Field Emission Scanning Electron Microscopy (FESEM). The synthesis approach involved the creation of nanoparticles with varying weights of TFNA, ranging from 0.3 to 1.6 wt. %, followed by calcination at 400 °C for 120 min in the presence of air. The resulting nanostructures were tested for their efficiency in degrading rhodamine B (RhB) dye under ultraviolet (UV) light irradiation. The experimental findings revealed that the 1.6 wt. % TFNA/TiO2 composite exhibited exceptional photocatalytic activity, with approximately 87.0 % degradation efficiency towards RhB dye in aqueous solutions under UV light. This remarkable performance can be attributed to the increased lifetime of photogenerated electron-hole pairs and accelerated interfacial charge transfer rates. [ABSTRACT FROM AUTHOR]

In this study high‐valent Cu(III) trifluoromethyl compounds in combination with DMSO is shown to be an efficient and mild oxidizing system for the conversion of alcohols to ketones (aldehydes as well). Trifluoromethoxylated sulfonium species is proposed to be initially formed that engages in crucial steps of alkoxy replacement at sulfonium center and deprotonative collapse of the resulting alkoxysulfonium intermediate in the presence of a base. This reaction is highly selective without over‐oxidation, and can tolerate a broad range of functional groups owing to mild oxidizing ability of the Cu(III)‐CF3/DMSO system and the inert N2 conditions. This method can be applied to the synthesis and functionalization of commercial drug compounds. This study illustrates an unusual reactivity property of high‐valent Cu(III) trifluoromethyl compounds beyond the conventional CF3 group transfer reactivity, and opens up new opportunities for developing novel reactions of Cu(III)‐CF3 compounds. The combined use of high‐valent Cu(III)‐CF3 compound and DMSO is anticipated to find more applications to develop other novel and useful oxidation reactions. [ABSTRACT FROM AUTHOR]

Amino acid-derived quaternary ammonium salts were successfully applied in the asymmetric aza-Henry reaction of nitromethane to N-Boc trifluoromethyl ketimines. a-Trifluoromethyl p-nitroamines were synthesized in good to excellent yields with moderate to good enantioselectivities. This reaction is distinguished by its mild conditions, low catalyst loading (1 mol%), and catalytic base. It also proceeded on a gram scale without loss of enantioselectivity. The products were transformed to a series of adamantane- type compounds containing chiral trifluoromethylamine fragments. The potent anticancer activities of these compounds against liver cancer HepG2 and melanoma B16F10 were evaluated. Six promising compounds with notable efficacy have potential for further development. [ABSTRACT FROM AUTHOR]

The selective C−F bonds functionalization in available trifluoromethyl compounds is an economic route for obtaining high‐value organic fluorine compounds. However, due to the high C−F bonds dissociation energy in trifluoromethyl group, the strength of the bond decreases continuously during defluorination, posing a challenge in modifying such molecules without over‐conversion. Over the past few years, there has been significant progress in developing efficient methods for constructing difluoromethylene unit, using approaches such as radical chemistry, photochemistry, electrochemistry, and organometallic chemistry. These methods involve difluorocarbon radicals, difluorocarbon cations, difluorocarbon anions, and trifluoromethyl carbenes as intermediates. In this review, we summarized the recent five years of research achievements in this field for selective single C−F bond cleavage in trifluoromethyl aromatic and carbonyl compounds to gain diverse difluoromethylene‐containing organic molecules via different intermediate strategies. [ABSTRACT FROM AUTHOR]

A robust and practical difluoroalkylation synthon, α,α‐difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting in dramatically improved enantioselectivity under mild conditions. As demonstrated in catalytic asymmetric aldol reaction and Mannich reactions with ketones or imines in the presence of chiral organocatalysts, quinine‐derived urea, and chiral phosphoric acid (CPA), respectively, this relay catalysis strategy provides an effective platform for applying asymmetric fluorination chemistry. Moreover, this method features a novel 1,2‐difunctionalization process via installation of a carbonyl motif and an alkyl group on two vicinal carbons, which is a complementary protocol to the metal carbene gem‐difunctionalization reaction. [ABSTRACT FROM AUTHOR]

The introduction of trifluoromethyl groups into organic molecules is of paramount importance in modern synthetic chemistry and medicinal chemistry. While methods for constructing C(sp2)−CF3 bonds have been well established, the advancement of practical and comprehensive approaches for forming C(sp3)−CF3 bonds remains considerably restricted. In this work, we describe an efficient and site‐specific deaminative trifluoromethylation reaction of aliphatic primary amines to afford the corresponding alkyl trifluoromethyl compounds. The reaction proceeds at room temperature with readily accessible N‐anomeric amide (Levin's reagent) and bench‐stable bpyCu(CF3)3 (Grushin's reagent, bpy=2,2′‐bipyridine) under blue light. The protocol features mild reaction conditions, good functional group tolerance, and moderate to good yields. Remarkably, the method can be applied to the direct, late‐stage trifluoromethylation of natural products and bioactive molecules. Experimental mechanistic studies were conducted, and a radical mechanism is proposed, wherein the dual roles of Grushin's reagent have been elucidated. [ABSTRACT FROM AUTHOR]

We herein describe a protocol to synthesize trifluoromethylated alkyl boronates from alkenes by the mutual activation of the Togni II and the bis(catecholato)diboron reagents in the absence of any catalyst and additives. This reaction enables synthesizing a series of trifluoromethylated alkyl boronates using unactivated alkenes, including natural products and drug derivatives, in a regioselective manner. Moreover, the synthetic utility of the boronic ester present in the product allows access to a range of trifluoromethyl containing compounds. The radical trapping and gas detection experiments reveal that the more Lewis acidic diboron reagent determines the rapid formation of trifluoromethyl and boron centered radicals. [ABSTRACT FROM AUTHOR]

The use of trifluoromethyl containing compounds is well established within medicinal chemistry, with a range of approved drugs containing C−CF3 and O−CF3 moieties. However, the utilisation of the N−CF3 functional group remains relatively unexplored. This may be attributed to the challenging synthesis of this unit, with many current methods employing harsh conditions or less accessible reagents. A robust methodology for the N‐trifluoromethylation of secondary amines has been developed, which employs an umpolung strategy in the form of a copper‐catalysed electrophilic amination. The method is operationally simple, uses mild, inexpensive reagents, and has been used to synthesise a range of novel, structurally complex N−CF3 containing compounds. [ABSTRACT FROM AUTHOR]

The first example for the generation of 2,2,2-trifluoroethylidene ylide from corresponding iodonium salt is reported, which has been successfully applied in the epoxidation of aldehydes, achieving the corresponding trifluoromethylated epoxides in high yields and diastereo-selectivities. [ABSTRACT FROM AUTHOR]

Trimethylsilyl ethers of trifluoromethyl substituted benzyl type alcohols of thiophene and (benzo)furan series undergo multichannel electrophilic transformations in triflic acid CF3SO3H (TfOH). Intermediate cationic species generated from starting heterocycles interact with arenes, leading to the formation of various products of side chain arylation, dehalogenation, arylation of the heteroaromatic core, intramolecular cyclization, hydro-detrimethylsilylogenation, oxo-dehalogenation, and others. The reaction pathway depends on the structure of an intermediate cation, nucleophilicity of the arene, reaction time, and temperature. Plausible mechanisms of these electrophilic reactions are discussed. The obtained trifluoromethyl substituted compounds exhibit good antimicrobial activity against Candida albicans, a yeast-like fungus, at concentrations ranging from 64 to 128 μg mL−1 and inhibit the growth of both Escherichia coli and Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerases (PARPs) are key enzymes in the DNA repair pathway. Inhibitors of these enzymes belong to a new type of anticancer drugs that selectively kill cancer cells by targeting the homologous recombination genetic defects. This study presents a new synthetic approach to PARP inhibitors containing a 4-trifluoromethyl substituted 3,6,7,7a-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-2,5-dione scaffold. The method is based on a practical one-step cyclocondensation of 2-(2-oxo-1,2,3,4-tetrahydropyrimidin-4-yl)acetic acid derivatives via the Curtius rearrangement of the corresponding acyl azides formed in situ upon the treatment with diphenylphosphoryl azide. The resulting products have been found to possess a potent inhibitory effect on PARP-1 and PARP-2 isoforms of poly(ADP-ribose) polymerases. The structure–activity analysis has revealed that the N1-aryl substituent is crucial to the selectivity and high potency towards PARP-2, and that the p-fluorobenzyl group is the optimal group for the non-selective and potent PARP-1 and PARP-2 inhibition [ABSTRACT FROM AUTHOR]

A positive synergy in the electric strength was observed in a previous study in SF6/HFO1234ze(E) mixtures which was shown to result from a strong electron energy moderation capability of HFO1234ze(E) combined with thermal electron attachment of SF6 (Egüz et al 2022 J. Phys. D: Appl. Phys. 55 315203). In the present work, the electron energy moderation properties of compounds with a similar C=C−C backbone are investigated. Swarm and breakdown measurements are performed in pure gases and in mixtures with SF6. Compounds with a trifluoromethyl group (−CF3) showed lower characteristic energy and as a consequence a positive synergism with SF6. Descriptors related to electron energy moderation are identified and computed; a clear trend is found from the analysis of descriptors related to inelastic processes which suggest(s) that vibrational excitations may be the main source of electron energy loss in the compounds showing positive synergy. [ABSTRACT FROM AUTHOR]

Single C−F transformations of aromatic trifluoromethyl compounds are challenging issues due to the strong C−F bond. We have recently developed selective methods for single C−F transformations such as allylation of o‐hydrosilyl‐substituted benzotrifluorides through the hydride abstraction with trityl cations. Single C−F thiolation and azidation of o‐(hydrosilyl)benzotrifluorides were achieved using trityl sulfides and trityl azide catalyzed by Yb(OTf)3. Treatment of o‐(hydrosilyl)benzotrifluorides with trityl chloride resulted in single C−F chlorination. The resulting fluorosilyl group served in further transformations including protonation, halogenation, and Hiyama cross‐coupling with C−Si cleavage. We also synthesized benzyl fluorides by LiAlH4‐reduction of the resulting fluorosilanes and further C−F transformations. These methods enabled us to prepare a broad range of organofluorines from simple benzotrifluorides through C−F and C−Si transformations. [ABSTRACT FROM AUTHOR]

The new high selective mAChRs M3 inhibitors with IC50 in nanomolecular ranges, which can be the prototypes for effective COPD and asthma treatment drugs, were discovered with computational approaches among trifluoromethyl containing hexahydropyrimidinones/thiones. Compounds [6‐(4‐ethoxy‐3‐methoxy‐phenyl)‐4‐hydroxy‐2‐thioxo‐4‐(trifluoromethyl)hexahydropyrimidin‐5‐yl]‐phenyl‐methanone (THPT‐1) and 5‐benzoyl‐6‐(3,4‐dimethoxyphenyl)‐4‐hydroxy‐4‐(trifluoromethyl)hexahydropyrimidin‐2‐one (THPO‐4) have been proved to be a highly effective (with IC50 values of 1.62 ⋅ 10−7 M and 3.09 ⋅ 10−9 M, respectively) at the same concentrations significantly competitive inhibit the signal conduction through mAChR3 in comparison with ipratropium bromide, without significant effect on mAChR2, nicotinic cholinergic and adrenergic receptors. [ABSTRACT FROM AUTHOR]

This account summarizes our recent efforts in the enantioselective organocatalytic synthesis of chiral halogenated compounds. The enantioselective α‐halogenation of aldehydes, decarboxylative chlorination of β‐keto acids, and enantioselective C−C bond formation at the trifluoromethylated prochiral carbon to yield the corresponding organohalides with chlorinated, fluorinated, or trifluoromethylated chiral stereogenic centers are discussed. We applied common organocatalysts, such as Jørgensen‐Hayashi catalyst and cinchona alkaloid‐derivatived catalyst, and developed novel chiral amine catalysts for these reactions. This account also discusses stereospecific derivatizations of the resulting chiral halogenated compounds via nucleophilic substitution. Thus, we synthesized many novel chiral compounds that have not been reported, even as racemates. [ABSTRACT FROM AUTHOR]

This study reports reactivity properties of Cu(III)−CF3 compounds with anilines, wherein basicity‐dictated distinct reactivities are achieved, giving rise to formamides or hydrazines. Competing generation of difluorocarbene and N‐centered radical is proposed that is controlled by the basicity of the reaction solution. Specifically, under acidic or neutral conditions, reaction of anilines with Cu(III)−CF3 compounds produces formamides, where difluorocarbene is involved, undergoing aniline formylation. In contrast, in the presence of a base, this same reaction selectively gives hydrazines instead, where Cu(III)−CF3 compounds act as an oxidizing reagent to allow dehydrogenative N−H/N−H coupling of two anilines through an N‐centered radical. The scope of both reactions is studied, and application to medicinally relevant compounds is shown. This study shows the unusual use of high‐valent Cu(III) trifluoromethyl compounds as hydrogen‐abstracting reagents to allow dehydrogenative reactions. [ABSTRACT FROM AUTHOR]

The difunctionalizative trifluoromethylation of unsaturated C−C bonds is a highly useful and efficient method for the synthesis of trifluoromethyl compounds with attractive architectures from simple feedstocks, allowing the introduction of the CF3 group along with a wide variety of substituents either inter‐ or intramolecularly. Given that trifluoromethyl molecules are increasingly used as promising bioactive species in the design of new drugs and agrochemicals, difunctionalizative trifluoromethylation has been extensively studied during the last decade. This review focuses on reactions proceeding via the simultaneous formation of C−heteroatom (O, N, S, Se, B) and C−H bonds, as these reactions provide useful CF3 group‐containing building blocks. To identify the trends and prospects of the evolution of this methodology, we systematically describe the variants of these types of reactions and provide a more general view of reaction conditions, modes, and mechanisms. The presented comprehensive survey enables the categorization of reactions into those that are synthetically mature and those with room for further development. [ABSTRACT FROM AUTHOR]

We report a kinetic study of the water exchange on lanthanide ions in water/[1-ethyl-3-methylimidazolium][trifluoromethylsufate] (water/[EMIm][OTf]). The results from 17O-NMR measurements show that the water-exchange rates in water/[EMIm][OTf] increase with decreasing size of the lanthanide ions. This trend forwater-exchange is similar to the previously reported trend inwater/1-ethyl-3-methylimidazolium ethyl sulfate (water/[EMIm][EtSO4]) but opposite to that in water. To gain atomic-level insight into these water-exchange reactions, molecular dynamics simulations for lanthanide ions in water/[EMIm][OTf] have been performed using the atomic-multipole-optimizedenergetics-for-biomolecular-application polarizable force field. Our molecular dynamics simulations reproduce the experimental water-exchange rates in terms of the trend and provide possible explanations for the observed experimental behavior. The smaller lanthanide ions in water/[EMIm][OTf] undergo faster water exchange because the smaller lanthanide ions coordinate to the first shell [OTf] anions more tightly, resulting in a stronger screening effect for the second-shell water. The screening effect weakens the interaction of the lanthanide ions with the second-shell water molecules, facilitating the dissociation of water from the second-shell and subsequent association of water molecules from the outer solvation shells. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Trifluoromethyl group is one of the most frequently available and promising functional groups in pharmaceutical, agrochemical as well as material molecules. Developing synthetic methods for the synthesis of trifluoromethyl functionalized compounds by trifluoromethylation reactions occupies significant position in modern organic chemistry. On the other hand, as a typical tool of sustainable synthesis, transition metal‐free synthesis possesses unique advantages in atom economy, easy product purification as well as excellent eco‐tolerance. Consequently, transition metal‐free trifluoromethylation reactions constitute the most important approaches for accessing trifluoromethylated molecules. Herein, the advances in the transition metal‐free C—H trifluoromethylation reactions are reviewed for the first time. According to the updated state‐of‐art, both the catalytic reactions by conventional heating chemistry and the more sustainable photocatalysis are included, covering the trifluoromethylation reactions of C(sp3)–H bond, aromatic C(sp2)–H bond as well as the non‐aromatic C(sp2)–H bond in different substrates over the last five years (2017—2021). [ABSTRACT FROM AUTHOR]

• DFT calculations elucidate the nickel-catalyzed defluorinative asymmetric cyclization reaction of trifluoromethyl-substituted 1,6-enynes via the stepwise addition cyclization mechanism. • The electrostatic interactions govern the regioselectivity of the reaction, favoring 1,2-insertion of the carbon-carbon triple bond over 2,1-insertion. • The enantioselectivity originates from stronger non-covalent interactions between the ligand and the substrate, minimal catalyst conformational distortion, and enhanced electronic interactions between the catalyst and the substrate. Density functional theory (DFT) calculations were employed to elucidate the mechanism and selectivity of nickel-catalyzed defluorinative asymmetric cyclization reactions of trifluoromethyl-substituted 1,6-enynes. The results indicate that the product is formed via a stepwise addition cyclization mechanism, including sequential steps of ligand coordination, transmetalation, ligand exchange, alkyne insertion, olefin insertion, β-F elimination, another transmetalation, and a final ligand exchange. The regioselectivity is primarily governed by the alkyne insertion step, where electrostatic interactions strongly favor 1,2-insertion of the carbon-carbon triple bond over 2,1-insertion. The enantioselectivity is largely determined during the insertion step of the olefin insertion step, with the (S)-product forming preferentially over the (R)-product due to stronger non-covalent interactions between the ligand and the substrate, minimal catalyst conformational distortion, and enhanced electronic interactions between the catalyst and the substrate. [Display omitted] [ABSTRACT FROM AUTHOR]

This paper describes the photophysical properties of a series of seven selected examples of 5-(alkyl/aryl/heteroaryl)-2-methyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidines (3), which contain alkyl, aryl, and heteroaryl substituents attached to the scaffolds of 3. Given the electron-donor groups and -withdrawing groups, the optical absorption and emission in the solid state and solution showed interesting results. Absorption UV–Vis and fluorescence properties in several solvents of a pyrazolo[1,5-a]pyrimidines series were investigated, and all derivatives were absorbed in the ultraviolet region despite presenting higher quantum emission fluorescence yields in solution and moderate emission in the solid state. Moreover, the solid-state thermal stability of compounds 3a–g was assessed using thermogravimetric analysis. The thermal decomposition profile showed a single step with almost 100% mass loss for all compounds 3. Additionally, the values of T0.05 are considerably low (72–187 °C), especially for compound 3a (72 °C), indicating low thermal stability for this series of pyrazolo[1,5-a]pyrimidines. [ABSTRACT FROM AUTHOR]

Fluorine‐containing moieties are widely used in the pharmaceutical, agrochemical, and material fields. Thus, these structures are of immense interest in the fields of organic synthesis and medicinal chemistry. Among various fluorinated groups, the difluoromethyl unit has drawn increasing attention due to its unique pharmaceutical properties. In recent years, several methods for the synthesis of difluoromethylated compounds have been rapidly developed. However, most of these methods treat aromatic compounds with excess difluoromethylating reagents, which often contain organometallic compounds, so these transformations are generally less environmentally friendly and atom‐economical. In this review, we summarize the recent development of new methods for the synthesis of difluoromethyl motifs or difluoroalkenes from trifluoromethylated aromatic compounds or trifluoromethyl alkenes via single C(sp3)−F bond cleavage. [ABSTRACT FROM AUTHOR]

The dynamics of methyl (CH3) and fluoromethyl (CF3) groups in organic molecular (van der Waals) solids can be exploited to survey their local environments.We report solid state 1H and 19F spin-lattice relaxation experiments in polycrystalline 3-trifluoromethoxycinnamic acid, along with an X-ray diffraction determination of the molecular and crystal structure, to investigate the intramolecular and intermolecular interactions that determine the properties that characterize the CF3 reorientation. The molecule is of no particular interest; it simply provides a motionless backbone (on the nuclear magnetic resonance (NMR) time scale) to investigate CF3 reorientation occurring on the NMR time scale. The effects of 19F-19F and 19F-1H spin-spin dipolar interactions on the complicated nonexponential NMR relaxation provide independent inputs into determining a model for CF3 reorientation. As such, these experiments provide much more information than when only one spin species (usually 1H) is present. In Sec. IV, which can be read immediately after the Introduction without reading the rest of the paper, we compare the barrier to CH3 and CF3 reorientation in seven organic solids and separate this barrier into intramolecular and intermolecular components. [ABSTRACT FROM AUTHOR]

We have carried out nonlinear ion conductivity measurements on the supercooled ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide[C6mim][NTf2] by applying ac electric fields with amplitudes up to about 200 kV/cm. At these field amplitudes, 3ω and 5ω harmonic components in the current response were detected, and the higher-order conductivity coefficients σ¹3,σ³3,σ³5, and σ55 were determined. The frequency and temperature dependence of these conductivity coefficients was analyzed in detail. The most important findings were the following: (i) The third-order spectra σ¹3 and σ³3 exhibit very similar values in the dc plateau regime but differ considerably in the dispersive regime. The same was observed for the fifth order spectra σ³5 and σ55. (ii) In the dispersive regime, the third-order spectra display a minimum, while the fifth-order spectra display a maximum. (iii) The frequencies of these minima and maxima are thermally activated with the same activation energy as the low-field dc conductivity σ1,dc, whereas the dc values of the higher-order conductivity coefficients, σ3,dc and σ5,dc, are characterized by lower activation energies. [ABSTRACT FROM AUTHOR]

Small molecules that contain the (TFMO) moiety were reported to specifically inhibit the class-IIa histone deacetylases (HDACs), an important target in cancer and the disorders of the central nervous system (CNS). However, radiolabeling methods to incorporate the [18F]fluoride into the TFMO moiety are lacking. Herein, we report a novel late-stage incorporation of [18F]fluoride into the TFMO moiety in a single radiochemical step. In this approach the bromodifluoromethyl-1,2,4-oxadiazole was converted into [18F]TFMO via no-carrier-added bromine-[18F]fluoride exchange in a single step, thus producing the PET tracers with acceptable radiochemical yield (3–5%), high radiochemical purity (> 98%) and moderate molar activity of 0.33–0.49 GBq/umol (8.9–13.4 mCi/umol). We validated the utility of the novel radiochemical design by the radiosynthesis of [18F]TMP195, which is a known TFMO containing potent inhibitor of class-IIa HDACs. [ABSTRACT FROM AUTHOR]

Four organic small-molecule hole transport materials (D41, D42, D43 and D44) of tetraarylpyrrolo[3,2-b]pyrroles were prepared. They can be used without doping in the manufacture of the inverted planar perovskite solar cells. Tetraarylpyrrolo[3,2-b]pyrroles are accessible for one-pot synthesis. D42, D43 and D44 possess acceptor-π-donor-π-acceptor structure, on which the aryl bearing substitutes of cyan, fluorine and trifluoromethyl, respectively. Instead, the aryl moiety of D41 is in presence of methyl with a donor-π-donor-π-donor structure. The different substitutes significantly affected their molecular surface charge distribution and thin-film morphology, attributing to the electron-rich properties of fused pyrrole ring. The size of perovskite crystalline growth particles is affected by different molecular structures, and the electron-withdrawing cyan group of D42 is most conducive to the formation of large perovskite grains. The D42 fabricated devices with power conversion efficiency of 17.3% and retained 55% of the initial photoelectric conversion efficiency after 22 days in dark condition. The pyrrolo[3,2-b]pyrrole is efficient electron-donating moiety for hole transporting materials to form good substrate in producing perovskite thin film. [ABSTRACT FROM AUTHOR]

Polyfluoromethyl groups generally suffer from over-reaction, where multiple C–F bonds are uncontrollably functionalized. The use of a frustrated Lewis pair (FLP)-mediated C–F bond activation permits selective monodefluorination through base capture of intermediate fluorocarbocations. FLP-mediated C–F bond activation can be applied to aromatic, heteroaromatic, or nonaromatic difluoro and trifluoromethyl groups to generate selectively fluoride-substituted phosphonium and pyridinium salts. These salts can be further functionalized by Wittig coupling, nucleophilic substitution, photoredox alkylation, nucleophilic transfer, or hydrogenation reactions to install a range of functional groups into the activated C–F position. 1 Introduction 2 Frustrated Lewis Pair C–F Activation 3 Conclusion [ABSTRACT FROM AUTHOR]

Two new iridium(III) complexes were synthesized by introducing two trifluoromethyl groups into an ancillary ligand to develop pure‐red emitters for organic light‐emitting diodes (OLEDs). The electron‐donating ability of the ancillary ligands is suppressed, owing to the electron‐withdrawing nature of trifluoromethyl groups, which can reduce the HOMO energy levels compared with those of compounds without trifluoromethyl groups. However, the introduction of trifluoromethyl groups into the ancillary ligand has little impact on the LUMO energy levels. Therefore, a well‐tuned, pure‐red, excited‐state energy was achieved by regulating the relative energy level between the HOMO and LUMO. OLEDs with these complexes as emitters showed high external quantum efficiencies (EQEs) of 26 % and realized high EQEs of about 25 % and fairly low driving voltages of 3.3–3.6 V for practical luminance of 1000 cd m−2, as well as excellent Commission Internationale de L'Eclairage (CIE) coordinates of (0.66, 0.33) and (0.67, 0.33); thus, this demonstrates the successful molecular design strategy by modifying the electron‐donating ability of ancillary ligand. [ABSTRACT FROM AUTHOR]

CF3CF=CF2 is a potential source of atmospheric trifluoroacetic acid (CF3C(O)OH). The kinetics of the reaction of the simplest Criegee intermediate (CH2OO) with CF3CF=CF2 was studied by using the OH laser-induced fluorescence method. At 10 torr, the rate co-efficients were measured to be (1.45±0.14)×10−13, (1.18±0.11)×10−13, (1.11±0.08)×10−13, and (1.04±0.08)×10−13 cm3·molecule−1·s−1 at 283, 298, 308 and 318 K, respectively. The activation energy of (−1.66±0.21) kcal/mol was derived from the Arrhenius equation. No obvious pressure dependence was observed. [ABSTRACT FROM AUTHOR]

This study reports an oxytrifluoromethylation method for construction of oxazoles and furans motif and the concurrent incorporation of a 2,2,2‐trifluoroethyl group at the aromatic C5‐position. High‐valent copper(III) trifluoromethyl compounds are crucial to this reaction that induces oxy‐trifluoromethylation of alkynes with a pendant amide/enol group functioning as the oxygen‐nucleophile. A wide substrate scope is demonstrated with high efficiency and with broad functional group tolerance. Late‐stage functionalization of dehydrocholic acid, a complex drug compound, is accomplished to show the potential of this method for practical drug design. [ABSTRACT FROM AUTHOR]

The high resolution rotational spectrum of 2-(trifluoromethyl)pyridine in 2 20 GHz was recorded and analyzed. Spectroscopic parameters including rotational constants, nuclear quadrupole coupling constants of 14N as well as the centrifugal distortion constants were determined. The rotational spectra of five mono-substituted 13C and one 15N isotopologues were also measured and assigned in natural abundance. Experimental results complemented by ab initio calculations lead to an accurate determination of the skeleton structure. The values of the planar moment inertia Pcc were determined to be 44.46 uÅ2 for all the measured isotopologues, indicating a Cs symmetry of this molecule. The molecular electrostatic surface potential was calculated to illustrate the trifluoromethyl substitution effects on the electron distribution. [ABSTRACT FROM AUTHOR]

The trifluoromethyl radical, CF3•, is studied for the first time by means of threshold photoelectron spectroscopy (TPES). The radical is produced in the gas phase using the flash-pyrolysis technique from hexafluoroethane as a precursor. CF3+ total ion yield and mass-selected TPES of the radical are recorded using a spectrometer based upon velocity map imaging and Wiley-McLaren time-of-flight coupled to the synchrotron radiation. The high resolution of the instrument and of the photons allows the observation of rich vibrational progressions in the TPES of CF3•. By using Franck-Condon factors computed by Bowman and coworkers, we have been able to simulate the TPES. The initial vibrational temperature of the radical beam has been evaluated at 350 ± 70 K. The structures have been identified as transitions between (n1,n2) and (n1+,n2+) vibrational levels of CF3 and CF3+ with small excitation of the breathing mode, ν1+, and large excitation (n2+ = 10-26) of the umbrella mode, ν2+, in the cation. From the energy separation between the two resolved peaks of each band, a value of 994 ± 16 cm-1 has been derived for the ν1+ breathing frequency of CF3+. For the high-lying n2+ levels, the apparent ν2+ umbrella spacing, 820 ± 14 cm-1, is fairly constant. Taking into account the ν2+ anharmonicity calculated by Bowman and coworkers, we have deduced ν2+ = 809 ± 14 cm-1, and semi-empirical estimations of the adiabatic ionization energy IEad.(CF3•) are proposed in good agreement with most of previous works. A value of the vertical ionization potential, IEvert.(CF3•) = 11.02 eV, has been derived from the observation of a photoelectron spectrum recorded at a fixed photon energy of 12 eV. [ABSTRACT FROM AUTHOR]

Trifluoromethyl group (CF 3) is a privilege scaffold in fluorine-containing drugs, agrochemicals and material science. Hence, the development of highly efficient methods for introducing trifluoromethyl group into organic molecules is of primary importance. Significant progress on trifluoromethylation strategies, including trifluoromethylation reagents and trifluoromethyl building blocks, has been made in past two decades. Among various trifluoromethylation methods, trifluoromethylation by using the trifluoromethyl building blocks has always played an important role. As a stable and easily available compounds, trifluoromethyl N -acylhydrazones have emerged into versatile trifluoromethyl building blocks for construction of trifluoromethylated nitrogen compounds, especially for trifluoromethyl nitrogen - heterocycles. This review gives an overview on the research progress to use trifluoromethyl N -acylhydrazones as trifluoromethyl building blocks for construction of trifluoromethyl compounds. [Display omitted] [ABSTRACT FROM AUTHOR]

A general and selective method is developed that allows direct vinylic C−H bond trifluoromethylation of 1,1‐diarylalkenes by a high‐valent copper(III) trifluoromethyl complex, producing biologically active trifluoromethylated alkenes (as well as trifluoromethylated carbocyclic compounds). This fundamental reactivity of Cu(III)−CF3 compounds has thus far been unknown. The presence of a tertiary amine is crucial to this reaction, acting as both a weak base and a single electron transfer (SET) promoter to abstract the vinylic hydrogen. This method starts from bulk olefins under cost‐effective conditions (without the need for external noble metal photocatalyst or stoichiometric amounts of oxidant), and thus is valuable for practical and sustainable applications. [ABSTRACT FROM AUTHOR]

Herein we report an unprecedented, convenient NHC‐catalyzed one‐pot cascade reaction to afford α,ω‐difunctionalized hydroxytrifluoromethyl alkynones and allenones in a single step. The critical fragile aliphatic aldehydes are introduced by a base‐mediated in situ Grob‐type fragmentation of their corresponding latent cyclic vinylogous hemiacetal triflate (VHAT) and γ‐hydroxy vinyl triflate (GHVT) precursors, avoiding typical problems and losses upon isolation. The ′demasked′ aldehydes are subsequently trapped by NHC‐catalyzed umpolung and further metal‐free C−C‐cross‐coupling to access a broad scope of terminally modified alkynyl or allenyl aliphatic, aromatic and heteroaromatic trifluoromethyl ketones as multifunctionalized, high‐value building blocks for advanced synthetic applications. Additional synthetic utility of this approach is demonstrated with the possibility for asymmetric variants using chiral NHC‐catalysts. [ABSTRACT FROM AUTHOR]

We report the development of photoredox‐catalyzed and copper‐promoted trifluoromethoxylation of arenediazonium tetrafluoroborates, with trifluoromethyl arylsulfonate (TFMS) as the trifluoromethoxylation reagent. This new method takes advantage of visible‐light photoredox catalysis to generate the aryl radical under mild conditions, combined with copper‐promoted selective trifluoromethoxylation. The reaction is scalable, tolerates a wide range of functional groups, and proceeds regioselectively under mild reaction conditions. Furthermore, mechanistic studies suggested that a Cs[Cu(OCF3)2] intermediate might be generated during the reaction. [ABSTRACT FROM AUTHOR]

A study of organic compounds that caused a serious taste and odor episode of water supply in two residential areas in Catalonia (N.E. Spain) was carried out. Sweet and paint/solvent odor were the main descriptors used by consumers. Some cases of sickness and nausea were also associated with drinking water consumption by the consumers. Closed-loop stripping analysis (CLSA) combined with sensory gas chromatography and gas chromatography mass spectrometry detection were used to study the problem. As a result, 3-(trifluoromethyl)phenol (CAS number 98-17-9) was for the first time identified as a responsible of an odor incident in drinking water. Concentration levels of this compound were up to 17,000 ng/L in groundwater and up to 600 ng/L in distributed water. Odor threshold in water for 3-(trifluoromethyl)phenol was determined as 13 ng/L (45 °C). [ABSTRACT FROM AUTHOR]

A novel synthetic method of the 1, 3, 5‐trinitro‐2, 2‐bis(trifluoromethyl)‐1,3,5‐triazinane (2) has been successfully developed. In addition to IR, 1H 13C NMR and elemental analysis, compound 2 was characterized by 15N NMR and X‐ray single crystal diffraction. Due to the introduction of trifluoromethyl, the density of compound 2 is up to 2.04 g⋅cm−3 at 298 K, which is consistent with its crystal density (2.059 g⋅cm−3, 296(2) K). Compound 2 exhibits excellent detonation pressures and velocities (P, 45.6 GPa; vD, 9564 m⋅s−1), as good as exceptional impact and friction sensitivities(IS, 22.5 J; FS, >360 J). Some of these values are better than the current benchmark explosives, such as 1, 3, 5‐trinitrodihydro‐1, 3, 5‐triazine (RDX) and cyclo‐1, 3, 5, 7‐tetramethylenene‐2, 4, 6, 8‐tetranitramine (HMX).It is a potential high energy density material. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of vinyl trifluoromethyl compounds from α, β‐unsaturated carboxylic acids and CF3SO2Na has been developed. This electrochemical decarboxylative trifluoro‐methylation was found to be highly stereoselective and afforded products in good yields with wide substrate scope under metal‐free and external chemical oxidant‐free conditions. [ABSTRACT FROM AUTHOR]

Abstract A novel aromatic trifluoromethyl (CF 3)-substituted triphenylamine (TPA)-based diamine was synthesized and subjected to polycondenstion with various commercial aromatic dianhydrides. The obtained polyimides exhibit excellent solubility in common organic solvents, including ethanol, allowing their processing in thin films under environmentally friendly conditions. These polymers possess superior thermal stability, up to 485 °C and high glass transition temperature. The photo-optical properties were investigated in detail and the results evidenced the existence of a dual intramolecular charge transfer (ICT) between TPA and CF 3 units, on one hand and triphenylamine and phthalimide, on the other hand, a feature rarely encountered at TPA-based polyimides. The occurrence of the FRET mechanism between these two ICT exited states that modulates the light emission toward yellow-orange spectral range is a totally novel aspect highlighted for this type of polymers. Prototype devices with ITO/PEDOT:PSS/polyimide/Ag configuration were also fabricated and preliminary investigations of the electrical characteristics were performed. Graphical abstract Image 1 Highlights • Triphenylamine-based polyimides with excellent organosolubility are synthesized. • The polymers possess high thermal stability, up to 485 °C and high T g. • Yellow-orange emission was achived due to the FRET mechanism. • The developed polyimides proved the ability for ambipolar transport characteristics. • Nonlinear Schottky behaviour was demonstrated in ITO/PEDOT:PSS/polyimide/Ag devices. [ABSTRACT FROM AUTHOR]

The chromenone core is an ubiquitous group in biologically active natural products and has been extensively used in organic synthesis. Fluorine-derived compounds, including those with a trifluoromethyl group (CF3), have shown enhanced biological activities in numerous pharmaceuticals compared with their non-fluorinated analogues. 2-Trifluoromethylchromenones can be readily functionalized at the 8- and 7-positions, providing chromenones cores of high structural complexity, which are excellent precursors for numerous trifluoromethyl heterocycles. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Transition-metal-free visible-light-induced trifluoromethylation of imidazopyridines. • Anthraquinone-2-carboxylic acid as the photo-organocatalyst. • Photoredox catalyzed cyclization generate trifluoromethyl radical. Abstract A transition-metal-free, visible-light-induced trifluoromethylation of imidazo[1,2- a ]pyridines has been developed at mild conditions by employing cheap and commercially available anthraquinone-2-carboxylic acid (AQN-2-CO 2 H) as the photo-organocatalyst, and Langlois reagent as the trifluoromethylating reagent. A series of 3-(trifluoromethyl)imidazo[1,2- a ]pyridine derivatives with broad functionalities could be conveniently and efficiently obtained by direct regioselective functionalization. [ABSTRACT FROM AUTHOR]

A one-pot transformation of α,β-unsaturated trifluoromethyl ketones with 2-(phenylsulfinyl)acetamide to give trifluoromethylated 2-pyridones is realized. The reaction proceeds under mild conditions and involves multiple steps in an expeditious and controlled sequence to provide efficient access to a broad range of trifluoromethylated 2-pyridones in moderate to high yields. Moreover, further synthetic manipulations permit the routine synthesis of a diverse array of trifluoromethylated pyridines with good efficiency. [ABSTRACT FROM AUTHOR]

Abstract Purpose To evaluate if the common field lampricide 3-trifluoromethyl-4-nitrophenol (TFM) that is intended to eradicate the invasive species sea lampreys in the Great Lakes has the potential to sensitize radiation responses in cells from non-targeted native fish Materials and methods The TFM toxicity was assessed acutely and chronically with the clonogenic fish cell line eelB. The acute toxicity (24-h exposure) was determined by the fluorescent cell viability probe Alamar Blue. The chronic toxicity was determined either by Alamar Blue (7-d exposure) or the clonogenic survival assay (14-d exposure). Pre- and post-exposure of fish cells to environmentally relevant TFM concentrations following gamma irradiation were performed. Clonogenic survival was determined to assess the damage level of radiation-induced reproductive cell death. Results The chronic toxicity tests were more sensitive than the acute toxicity tests. The 14-d EC 50 using the clonogenic survival endpoint was 2.09 ± 0.28 μg/mL and was statistically similar to the 7-d EC 50 (1.85 ± 0.07 μg/mL) based on the Alamar Blue-based cytotoxicity endpoint. Post-exposure of cells to environmentally relevant TFM concentrations following irradiation did not have any effect as compared to the irradiation alone group. In contrast, pre-exposure of cells to TFM following irradiation had a negative additive effect when the total radiation dose was 2 Gy, but not 0.1 or 0.5 Gy. Conclusion Our results suggest that the common field lampricide TFM is a potential radiation sensitizer in cells from non-targeted native fish. This could be a health problem of concern for non-targeted native fish if a large accidental radioactive release occurs. Highlights • Effects of the lampricide TFM on the fish cells' reproductive death were studied. • Chronic TFM toxicity tests were more sensitive than acute toxicity tests. • Post-exposure of fish cells to TFM has no additive effect on the radiation responses. • Pre-exposure of fish cells to TFM sensitizes the radiation responses. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A new series of Xanthenone based hydrazones (5a–n) was synthesized. • New hydrazones were screened for their i n vitro α -glucosidase inhibitory activity. • Structure activity relationship established. • In silico , molecular docking was carried out to study putative binding of potent hydrazones with target enzyme. • Solid state self-assembly studies to explore the role of iminoamide dimer synthon in crystal packing. Abstract Xanthenone based hydrazone derivatives (5a–n) have been synthesized as potential α-glucosidase inhibitors. All synthesized compounds (5a–n) are characterized by their FTIR, 1H NMR, 13C NMR and HRMS, and in case of 5g also by X-ray crystallographic technique. The compounds unveiled a varying degree of α-glucosidase inhibitory activity when compared with standard acarbose (IC 50 = 375.38 ± 0.12 µM). Amongst the series, compound 5l (IC 50 = 62.25 ± 0.11 µM) bearing a trifluoromethyl phenyl group is found to be the most active compound. Molecular modelling is performed to establish the binding pattern of the more active compound 5l, which revealed the significance of substitution pattern. The pharmacological properties of molecules are also calculated by MedChem Designer which determines the ADME (absorption, distribution, metabolism, excretion) properties of molecules. The solid state self-assembly of compound 5g is discussed to show the conformation and role of iminoamide moiety in the molecular packing. [ABSTRACT FROM AUTHOR]