Trifluoromethoxy Group Research Articles

Cobalt‐Promoted Para C─H Amination of 3‐Acetyl Substituted Nitroarenes with Arylhydrazines

AbstractWe report a method to furnish substituted 1H‐indazoles via a coupling of 3‐acetyl substituted nitroarenes and arylhydrazines. Reactions progressed in the presence of cobalt(II) acetylacetonate catalyst, TEMPO oxidant, and Cs2CO3 base. Functional groups including bromo, chloro, nitro, and trifluoromethoxy groups were compatible with reaction conditions. The proposed mechanism was based on a nucleophilic substitution of hydrogen para to nitro group. Our method feature a convenient pathway to directly obtain substituted 1H‐indazoles which avoid the use of pre‐functionalized starting materials. Indazole could play a role as the directing group for a palladium‐catalyzed C(sp2)─H arylation with iodobenzene.

5-Trifluoromethoxy-substituted Nicotinic Acid, Nicotinamide and Related Compounds

A practical and convenient method for synthesizing nicotinic acid and nicotinamide with the trifluoromethoxy group in position 5 of the ring has been developed. A series of related compounds, for example, nicotinic aldehyde and nicotinic alcohol, have been synthesized. It has been shown that 3-bromo-5-trifluoromethoxypyridine is a convenient and efficient synthon for palladium-catalyzed coupling reactions. The trifluoromethoxy group has been found to be remarkably stable against hydroiodic acid in contrast to the methoxy group.

Copper‐Catalyzed Aerobic Benzylic C(sp3)−H Oxidation of Unprotected Aniline Derivatives for the Synthesis of Phenanthridines

AbstractHerein, we report a copper‐catalyzed intramolecular benzylic C(sp3)−H oxidation of unprotected aniline derivatives under aerobic conditions, which enables the preparation of phenanthridine compounds. To the best of our knowledge, this is the pioneering reaction of dehydrogenative C(sp3)−N bond formation from unprotected anilines under a Cu/O2 system. Notably, various anilines possessing alkyl, methoxy, halogen (fluoride, chloride, bromide, and iodide), trifluoromethyl, trifluoromethoxy, cyano, ester, and acetal groups can also participate in the reaction.

Conjugating uncoupler compounds with hydrophobic hydrocarbon chains to achieve adipose tissue selective drug accumulation

One potential approach for treating obesity is to increase energy expenditure in brown and white adipose tissue. Here we aimed to achieve this outcome by targeting mitochondrial uncoupler compounds selectively to adipose tissue, thus avoiding side effects from uncoupling in other tissues. Selective drug accumulation in adipose tissue has been observed with many lipophilic compounds and dyes. Hence, we explored the feasibility of conjugating uncoupler compounds with a lipophilic C8-hydrocarbon chain via an ether bond. We found that substituting the trifluoromethoxy group in the uncoupler FCCP with a C8-hydrocarbon chain resulted in potent uncoupling activity. Nonetheless, the compound did not elicit therapeutic effects in mice, likely as a consequence of metabolic instability resulting from rapid ether bond cleavage. A lipophilic analog of the uncoupler compound 2,6-dinitrophenol, in which a C8-hydrocarbon chain was conjugated via an ether bond in the para-position (2,6-dinitro-4-(octyloxy)phenol), exhibited increased uncoupling activity compared to the parent compound. However, in vivo pharmacokinetics studies suggested that 2,6-dinitro-4-(octyloxy)phenol was also metabolically unstable. In conclusion, conjugation of a hydrophobic hydrocarbon chain to uncoupler compounds resulted in sustained or improved uncoupling activity. However, an ether bond linkage led to metabolic instability, indicating the need to conjugate lipophilic groups via other chemical bonds.

2'-19F labelling of ribose in RNAs: a tool to analyse RNA/protein interactions by NMR in physiological conditions.

Protein-RNA interactions are central to numerous cellular processes. In this work, we present an easy and straightforward NMR-based approach to determine the RNA binding site of RNA binding proteins and to evaluate the binding of pairs of proteins to a single-stranded RNA (ssRNA) under physiological conditions, in this case in nuclear extracts. By incorporation of a 19F atom on the ribose of different nucleotides along the ssRNA sequence, we show that, upon addition of an RNA binding protein, the intensity of the 19F NMR signal changes when the 19F atom is located near the protein binding site. Furthermore, we show that the addition of pairs of proteins to a ssRNA containing two 19F atoms at two different locations informs on their concurrent binding or competition. We demonstrate that such studies can be done in a nuclear extract that mimics the physiological environment in which these protein-ssRNA interactions occur. Finally, we demonstrate that a trifluoromethoxy group (-OCF3) incorporated in the 2'ribose position of ssRNA sequences increases the sensitivity of the NMR signal, leading to decreased measurement times, and reduces the issue of RNA degradation in cellular extracts.

Recent developments in fluorine-containing pesticides.

To ensure ongoing sustainability, the modern agrochemical industry is faced with enormous challenges. These arise from provision of high-quality food to increasing water use and environmental impact as well as a growing world population. The loss of previous agrochemicals due to consumer perception, changing grower needs and ever-changing regulatory requirements is higher than the number of active ingredients that are being introduced into the crop protection market. Therefore, the development of novel agrochemicals is essential to provide improved efficacy and environmental profiles. In this context, the introduction of fluorine atoms and fluorine-containing motifs into a molecule is an important method to influence its physicochemical properties. These include, for example, small difluoro- and trifluoromethyl, or trifluoromethoxy groups at aryl or heterocyclic aryl moieties but also fragments like 2,2,2-trifluoroethoxycarbonyl, trifluoromethylsulfonyl, trifluoroacetyl, as well as the so far unusal rest like heptafluoro-iso-propyl. This review gives an overview of recent developments of fluorine-containing pesticides launched over the past 7 years and describes a selection of current fluorine-containing development candidates. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Metal-free introduction of primary sulfonamide into electron-rich aromatics.

We report herein a direct and practical synthesis of arylsulfonamides from electron-rich aromatic compounds by using in situ generated N-sulfonylamine as the active electrophile. Substrates include derivatives of aniline, indole, pyrrole, furan, styrene and so on. The reaction proceeds under mild conditions and tolerates many sensitive functional groups such as alkyne, acetate, the trifluoromethoxy group or acetoxymethyl ester. Applications of this method for the construction of metal ion sensors and fluorogenic dye have been demonstrated, thus highlighting the potential of this method for probe development.

Influence of the molecular structure of compounds differing with terminal polar group on the induction of the smectic A phase. Part III

ABSTRACT The aim of this work is to determine the influence of the terminal polar group of nematic compounds, namely -OCF3, -NCS, -CN, -F, on the induction of the SmA phase in their mixtures with compounds having terminal non-polar groups. The former group of compounds has positive dielectric anisotropy, and the latter negative. The phase transition temperatures of binary mixtures were measured using polarising thermomicroscopy, and phase diagrams for investigated systems were constructed. The strength of the SmA phase induction increases upon the increase of the polarity of compounds. The strongest induction is observed in systems with compounds having a terminal trifluoromethoxy group. Although compounds with the cyano group have the highest polarity, their ability for the SmA phase induction is smaller due to their dimerisation.

Bridging organic, molecular, macromolecular, supramolecular and biological sciences to create functions via fluorine chemistry and fluorinated reagents

After a brief introduction highlighting the challenges of fluorine chemistry and the latest developments in the field, this Perspective will discuss how a combination of fluorine and fluorous chemistry together with fluorinated reagents helped to bridge between organic, molecular, macromolecular, supramolecular and biological sciences to create functions in the laboratory of the corresponding author. The reactivity of fluoride as a leaving group is best illustrated by SNAr reactions when it helped to demonstrate single electron transfer-mediated side reactions and through molecular design replaced activated aryl fluorides with aryl chlorides in the synthesis of poly(etherketone)s. Subsequently it was demonstrated how Ni(II) sigma complexes provided an orthogonal approach to the Suzuki-type cross-coupling of arylfluorides, other halides and all aryl C–O based electrophiles. Fluorinated reagents facilitated cylotrimetrization vs cyclotetramerization of bis(methoxy)benzyl chloride and alcohol and the synthesis of the simplest molecular liquid crystals. Triflic acid, methyl triflate facilitated the most tolerant living polymerizations including of cyclic siloxanes, functional vinyl ethers and oxazolines to generate self-organizable dendronized polymers while fluorine, trifluoromethyl and trifluoromethoxy groups facilitated disassembly and reassembly of liquid crystal polyethers and poly(p-phenylenes). Fluorinated stereocenters accessed the first heterochiral recognition in side-chain liquid crystal poly(vinyl ether)s and their model compounds. Alkali metal triflates mediated self-organization of supramolecular nonfluorinated and fluorinated self-assembling minidendrons, dendrons, dendrimers and self-organizable dendronized polymers. The role of fluorinated alkyl groups and of alkali metal triflates in the self-assembly, disassembly and isomorphic replacement analysis, of supramolecular helical columns, of the assembly of helical cogwheel coat and of spherical supramolecular dendrimers forming Frank-Kasper periodic and quasiperiodic arrays was highlighted. A brief discussion of fluorinated amino acids, peptides and peptoids and their potential role in the self-assembly and functions resulted from dendritic dipeptides followed by a discussion of semifluorinated amphiphilic Janus dendrimers as models of biological membranes, including for cell fusion and fission, concludes this Perspective.

Design, Synthesis and Antifungal Activities of Novel Pyrazole Analogues Containing the Aryl Trifluoromethoxy Group.

On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF3 were designed and synthesized. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry. These compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi by the mycelium growth rate method. Most of the compounds showed some activity against each of the fungi at 100 μg/mL. Compounds 1t and 1v exhibited higher activity against all the tested fungi, and 1v displayed the highest activity against F. graminearum with an EC50 value of 0.0530 μM, which was comparable with commercial pyraclostrobin. Structure-activity relationship analysis showed that, with respect to the R1 substituent, the straight chain or cycloalkyl ring moiety was a key structural moiety for the activity, and the R2 substituent on the pyrazole ring could have significant effects on the activity. Simple and readily available pyrazoles with potent antifungal activity were obtained, which are ready for further elaboration to serve as a pharmacophore in new potential antifungal agents.

Synthesis and cis-trans kinetics of an azobenzene-based molecular switch for light-responsive silica surfaces

Light-responsive materials design is an attractive research field that stimulates demand for the synthesis of novel molecular photoswitches. The novel photoswitches should be capable of being attached to a desired surface in order to provide it with light-responsive properties. The switchback to its ground state is expected to be gradual, with the possibility of acceleration. This study presents a comprehensive description of a chemical route to a molecular photoswitch based on an azobenzene derivative with a trifluoromethoxy group and a long alkyl chain. The photoswitch is capable of modifying submicrometer silica particles and silicon wafers as models of curved and flat surfaces, respectively. The thermal relaxation times of the synthesized azobenzene were studied in three different solvents: ethanol, chloroform, and toluene. The results reveal a significantly delayed relaxation process lasting for several days. This observation is found to be related to the polarity of the solvents used. To characterize the extensive thermal relaxation process, a methodology including the use of white-light pulses to accelerate cis-trans isomerization is suggested. The white light spectrum used in pulses affects thermal relaxation but does not alter the relaxation time extrapolated to zero. The density of the photoswitch molecules attached to particles varies from 0.7 to 1.7 molecules/nm2 as the initial amount of azobenzene in the reaction increases. Surface-attached photoswitches demonstrate reversible cis-trans isomerization behavior when exposed to UV and white light irradiation. A 14° contact angle change is observed when flat surfaces modified with photoswitches are irradiated with UV light.

Precise Pore Engineering of fcu-Type Y-MOFs for One-Step C2 H4 Purification from Ternary C2 H6 /C2 H4 /C2 H2 Mixtures.

The purification of C2 H4 from C2 H6 /C2 H4 /C2 H2 mixtures is of great significance in the chemical industry for C2 H4 production but remains a daunting task. Guided by powerful reticular chemistry principles, herein a systematic study is carried out to engineer pore dimensions and pore functionality of fcu-type Y-based metal-organic frameworks (Y-MOFs) through the construction of a series of eight new structures using linear dicarboxylate linkers with different length and functional groups. This study illustrates how delicate changes in pore size and pore surface chemistry can effectively influence the adsorption preference of C2 H6 , C2 H4 , and C2 H2 by the MOFs. Importantly, clear relations between pore size/pore surface polarity and C2 adsorption selectivities of this series of MOFs are established. In particular, HIAM-326 built on a linker decorated with trifluoromethoxy group shows notably preferential adsorption of C2 H6 and C2 H2 over C2 H4 , with balanced C2 H2 /C2 H4 and C2 H6 /C2 H4 selectivities. This endows the compound with the capability of one-step purification of C2 H4 from C2 H6 /C2 H4 /C2 H2 ternary mixtures, which is validated by breakthrough measurements where high purity C2 H4 (99.9%+) can be obtained directly from the separation column. Its adsorption thermodynamics and underlying selective adsorption mechanisms are further revealed by ab initio calculations.

Design and synthesis of novel poly (aryl ether ketones) containing trifluoromethyl and trifluoromethoxy groups

ABSTRACTThe high-frequency and high-speed communication in the 5 G era puts forward requirements for the dielectric properties of polymers. Introducing fluorine into poly(ary ether ketone) can improve its dielectric properties. In this work, by introducing the fluorine group strategy, we successfully designed and synthesized three novel trifluoromethyl (−CF3) or trifluoromethoxy (−OCF3)-containing bisphenol monomers and their F-substitution PEK-based polymers (PEK-Ins). All these PEK-Ins exhibited good thermal, mechanical and dielectric properties. The T d5% of the three polymers is all higher than 520℃. The free volume fraction of novel polymers increased from 3.75% to 5.72%. Among the three polymers, exhibited the lowest dielectric constant of the films is 2.839, and the dielectric loss is 0.0048, ascribing to the increasing free volume. The Young’s modulus of the polymer film is as high as 2.9 GPa and the tensile strength is as high as 84 MPa. PEK-Ins reduced the dielectric constant by introducing a low fluorine content. This study provides a new way to design PEK to synthesize low dielectric constant polymers.

Copper-Catalyzed Enantioselective Trifluoromethoxylation of Propargyl Sulfonates.

Due to the strong electron-withdrawing nature and high lipophilicity of trifluoromethoxy group (OCF3 ), methods for introducing OCF3 into organic molecules are in high demand. However, the research area of direct enantioselective trifluoromethoxylation is still in the embryonic stage, with limited enantioselectivity and/or reaction types. Here, we describe the first copper-catalyzed enantioselective trifluoromethoxylation of propargyl sulfonates using trifluoromethyl arylsulfonate (TFMS) as the trifluoromethoxy source in up to 96 % ee.

Copper‐Catalyzed Enantioselective Trifluoromethoxylation of Propargyl Sulfonates

AbstractDue to the strong electron‐withdrawing nature and high lipophilicity of trifluoromethoxy group (OCF3), methods for introducing OCF3into organic molecules are in high demand. However, the research area of direct enantioselective trifluoromethoxylation is still in the embryonic stage, with limited enantioselectivity and/or reaction types. Here, we describe the first copper‐catalyzed enantioselective trifluoromethoxylation of propargyl sulfonates using trifluoromethyl arylsulfonate (TFMS) as the trifluoromethoxy source in up to 96 % ee.

Chiral nitroxide radical with terminal trifluoromethoxy group

ABSTRACTA new chiral liquid crystalline nitroxide radical with a terminal trifluoromethoxy group exhibits not only chiral nematic and chiral smectic A phases but also a twist grain boundary phase in the cooling process. The layer order induced by the trifluoromethoxy group seems frustrated with the helical order.

Influence of the molecular structure of calamitic compounds with trifluoromethoxy terminal group on the induction of the smectic a phase. Part I

ABSTRACT For the liquid crystalline mixtures of compounds with positive and negative dielectric anisotropies, the induction of the liquid crystal smectic A phase can be observed. This effect can be very favourable for definite specific purposes. The main aim of this work is to determine the influence of the molecular structure of compounds with a polar trifluoromethoxy (-OCF3) group on the induction strength of the orthogonal smectic A (SmA) phase. In order to reach this target, the phase diagrams of the mixtures were established using the polarised optical microscope observations. The presence of a triple bond, phenyl and cyclohexyl rings as well as fluorine atoms in the core and the length of terminal alkyl chains of the tested compounds were considered. The length of the rigid core has the greatest effect on the induction strength of the SmA phase, while the length of the alkyl chain (3–5 carbon atoms) has relatively minor influence. Explaining the correlation between the molecular structure and the induction strength, the dipole moments and the polarisability of the molecules should be taken into account. For shorter molecules, changes in the molecular structure have more significant influence on the temperature and concentration range of the orthogonal SmA phase.

Synthesis of Novel α-Trifluoroanisole Derivatives Containing Phenylpyridine Moieties with Herbicidal Activity.

To find novel herbicidal compounds with high activity and broad spectrum, a series of phenylpyridine moiety-containing α-trifluoroanisole derivatives were designed, synthesized, and identified via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Greenhouse-based herbicidal activity assays revealed that compound 7a exhibited > 80% inhibitory activity against Abutilon theophrasti, Amaranthus retroflexus, Eclipta prostrate, Digitaria sanguinalis, and Setaria viridis at a dose of 37.5 g a.i./hm2, which was better than fomesafen. Compound 7a further exhibited excellent herbicidal activity against Abutilon theophrasti and Amaranthus retroflexus in this greenhouse setting, with respective median effective dose (ED50) values of 13.32 and 5.48 g a.i./hm2, both of which were slightly superior to fomesafen (ED50 = 36.39, 10.09 g a.i./hm2). The respective half-maximal inhibitory concentration (IC50) for compound 7a and fomesafen when used to inhibit the Nicotiana tabacum protoporphyrinogen oxidase (NtPPO) enzyme, were 9.4 and 110.5 nM. The docking result of compound 7a indicated that the introduction of 3-chloro-5-trifluoromethylpyridine and the trifluoromethoxy group was beneficial to the formation of stable interactions between these compounds and NtPPO. This work demonstrated that compound 7a could be further optimized as a PPO herbicide candidate to control various weeds.

Polyimide Films Containing Trifluoromethoxy Groups with High Comprehensive Performance for Flexible Circuitry Substrates

Polyimide Films Containing Trifluoromethoxy Groups with High Comprehensive Performance for Flexible Circuitry Substrates

Synthesis and applications of S-(trifluoromethyl)-2,8-bis(trifluoromethoxy)dibenzothiophenium triflate (Umemoto reagent IV)

A new, powerful, and easy-to-handle electrophilic trifluoromethylating agent, S-(trifluoromethyl)-2,8-bis(trifluoromethoxy)dibenzothiophenium triflate (Umemoto reagent IV), was developed. Due to the extraordinary electronic effect of trifluoromethoxy group, Umemoto reagent IV was easily synthesized by a one-pot method from readily available 3,3’-bis(trifluoromethoxy)biphenyl. It was shown that Umemoto reagent IV was more powerful than Umemoto reagent II and could trifluoromethylate many kinds of nucleophilic substrates more effectively. In addition, Umemoto reagent IV was successfully utilized for the preparation of trifluoromethyl nonaflate, a useful trifluoromethoxylating agent. The direct conversion of 2,8-bis(trifluoromethoxy)dibenzothiophene to Umemoto reagent IV with triflic anhydride was achieved, albeit in low yield.