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Trans-4-(Trifluoromethyl) cinnamic acid (4TFCA) has a -C=C-double bond among the aromatic system and the carboxyl ring which disturbed the π-electrons of the molecule. The geometrical parameters of 4TFCA is computed using the DFT/B3LYP by higher basis set (6-311++G(d,p)) and the frontier molecular orbital analysis is achieved. FTIR and FTRaman spectra of 4TFCA have been obtained in the regions 4000-400 cm-1 and 4000-50 cm-1. The experimental vibrational frequencies are in good coordination with the calculated wavenumbers. The absorption spectra of 4TFCA have been calculated by using the time dependent/density functional theory approach. The stability of a molecule rising from hyperconjugative π →π* exchanges and charge delocalization has been calculated using natural bond orbital (NBO) analysis. The thermodynamic and charge responses have been studied. In addition, the results of molecular docking reveal that the molecule 4TFCA has the highest binding energy (-6.10 kcal/mol) with the histone deacetylase inhibitor (HDAC8). To understand the molecule's drug likeness, ADMET analysis has also been studied. [ABSTRACT FROM AUTHOR]

An efficient and green approach for the synthesis of azo dyes has been developed via the Brønsted acidic ionic liquid (IL) promoted diazo coupling reaction of naphthols with aryltriazenes. The reaction was carried out with the aryltriazenes as diazotizing agents, the Brønsted acidic ionic liquids as the promoter, and water as the green solvent at room temperature under air and metal-free conditions. Notably, the attractive advantages of the process include mild conditions with excellent yields, simple product isolation process, large-scale experiment, late-stage modification of pharmaceutical and recyclability of the promoter. In addition, the UV-vis spectral characteristics of the azo-dyes were investigated in DMSO. [ABSTRACT FROM AUTHOR]

Trifluoromethyl ketones (TFMKs) are electrophilic moieties which hydrate readily in aqueous media to give geminal diols. This ability has been exploited for the development of histone deacetylase (HDAC) inhibitors, because HDAC enzymes contain a Zn2+ ion which may be chelated by this functionality. Interestingly, TFMKs are exceptional Zn2+-binding groups for targeting the intriguing class IIa HDAC isozymes, involved in transcription factor recruitment and gene regulation. Here, we have developed a scalable and inexpensive synthetic procedure for preparation of the enantiomerically pure TFMK-containing amino acid building block (S)-2-amino-9,9,9-trifluoro-8-oxononanoic acid (Atona). In addition, we propose a protecting group strategy applicable to automated solid-phase peptide synthesis and demonstrate the ability of Atona-containing peptides to inhibit the enzymatic activity of class IIa HDACs with nanomolar potency. We envision that this synthesis will motivate the further development of peptide-based probes for the study of class IIa HDACs. [ABSTRACT FROM AUTHOR]

We have described CsF-catalyzed trifluoromethylation of heteroaromatic aldehydes at room temperature to afford trifluoromethyl group containing alcohols in very good yields. Using catalytic amount of CsF (0.2 eq.) in toluene, trifluoromethylated products were achieved in good yields at rt. The substrate scope has been exemplified by a large number of substrates. As an application, iodo etherification/cyclization has also been demonstrated for the synthesis of trifluoromethyl pyrano[4,3- b ]quinoline from o-alkynyltrifluoro methyl alcohol, in very good yield. [ABSTRACT FROM AUTHOR]

A series of novel 6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives were obtained in good yields from ethyl 4,4,4-trifluoro-3-oxobutanoate, urea, and aryl aldehyde via Biginelli multicomponent reaction. All the corresponding products 4a-4p were examined against four human cancer cell lines (A549, HepG2, COLO205 and DU145) and compounds 4e, 4i, and 4 m which showed promising anticancer activity have been identified. [ABSTRACT FROM AUTHOR]

This review provides an overview of the various synthetic pathways of the N -CF 3 group. This pattern can be generated either from fluoride ions or from electrophilic, nucleophilic, or radical trifluoromethylation. This article mainly focuses on the most recent and prominent studies. [ABSTRACT FROM AUTHOR]

A series of 2-(4-trifluoromethylphenyl)- and 2-trifluoromethyl-9-dialkylaminoalkylimidazo[1,2- a]benzimidazoles were synthesized for the first time by reacting 2-amino-1-dialkylaminoalkylbenzimidazoles and 2-bromo-1-[(4-trifluoromethyl)phenyl]ethanone or 1-bromo-3,3,3-trifluoroacetone and were tested for analgesic and antiplatelet activity, glycogen phosphorylase and dipeptidyl peptidase-4 inhibitory activity, and in vitro glycation of bovine serum albumin. [ABSTRACT FROM AUTHOR]

Abstract: A large number of reagents have been developed for the synthesis of trifluoromethylated compounds. However, an ongoing challenge in trifluoromethylation reaction is the use of less expensive and practical trifluoromethyl sources. We report herein the unprecedented direct trifluoromethylation of (hetero)arenes using trifluoromethanesulfonic anhydride as a radical trifluoromethylation reagent by merging photoredox catalysis and pyridine activation. Furthermore, introduction of both the CF3 and OTf groups of the trifluoromethanesulfonic anhydride into internal alkynes to access tetrasubstituted trifluoromethylated alkenes was achieved. Since trifluoromethanesulfonic anhydride is a low‐cost and abundant chemical, this method provides a cost‐efficient and practical route to trifluoromethylated compounds. [ABSTRACT FROM AUTHOR]

A simple and efficient synthetic approach is reported for the synthesis of 5-trifluoromethyl-5-aryl-3-methylidenepyrrolidin-2-ones in moderate to excellent yields via an acid-catalyzed one-pot multicomponent reaction of aromatic trifluoromethyl ketones, acylhydrazines, and ethyl 2-(bromomethyl)acrylate promoted by tin powder. The protocol is operationally simple. The overall process involves allylation and cyclization of the intermediate of acylhydrazones. [ABSTRACT FROM AUTHOR]

Electrophilic fluorination and fluoroalkylation are one of the most promising and efficient strategies in the synthesis of organofluorine compounds. The rapid progress of this field has been made possible by the emergence of a wide variety of power-variable, readily prepared, and easy-to-handle electrophilic fluorinating and fluoroalkylating reagents. Understanding the relative power of these reagents is thus vital for their use in synthetic transformations. This digest will outline some recent efforts to quantitatively ordering the relative power of electrophilic fluorinating, trifluoromethylating, and trifluoromethylthiolating reagents. [ABSTRACT FROM AUTHOR]

Abstract: A novel rhodium(III)‐catalyzed synthesis of 2‐(trifluoromethyl)‐dibenzopyranones from easily available 4‐(trifluoromethyl)‐p‐quinols and N‐methoxyarylamides is described. Rhodium(III)‐catalyzed formal anti‐Michael addition was proposed to be a crucial step in this [3+3] annulation with N‐methoxyarylamides as effective 1,3‐dipoles, providing a concise and efficient approach for the construction of trifluoromethyl‐containing dibenzopyranones under mild reaction conditions. [ABSTRACT FROM AUTHOR]

The trifluoromethyl tetrafluoro-λ6-sulfanyl (CF3SF4) group is both extraordinarily lipophilic and profoundly electron withdrawing, properties associated with polar hydrophobicity. Utilization of the CF3SF4 group to prepare novel materials or biologically active agents will not be possible without new methods for the synthesis of aliphatic CF3SF4-substituted building blocks. To advance those studies, trichloromethanesulfenyl chloride was conveniently converted to trans-trifluoromethyl tetrafluoro-λ6-sulfanyl chloride (CF3SF4Cl) by oxidative chlorofluorination. Triethylborane-promoted addition reactions of trans-CF3SF4Cl to substituted olefins and alkynes yielded a variety of new materials. Those addition products were subsequently transformed to CF3SF4-substituted carboxylic acids, CF3SF4-substituted ketones, and a CF3SF4-substituted aldehyde. [ABSTRACT FROM AUTHOR]

Abstract: Visible‐light capture activates a thermodynamically inert CoIII−CF3 bond for direct C−H trifluoromethylation of arenes and heteroarenes. New trifluoromethylcobalt(III) complexes supported by a redox‐active [OCO] pincer ligand were prepared. Coordinating solvents, such as MeCN, afford green, quasi‐octahedral [(SOCO)CoIII(CF3)(MeCN)2] (2), but in non‐coordinating solvents the complex is red, square pyramidal [(SOCO)CoIII(CF3)(MeCN)] (3). Both are thermally stable, and 2 is stable in light. But exposure of 3 to low‐energy light results in facile homolysis of the CoIII−CF3 bond, releasing .CF3 radical, which is efficiently trapped by TEMPO. or (hetero)arenes. The homolytic aromatic substitution reactions do not require a sacrificial or substrate‐derived oxidant because the CoII by‐product of CoIII−CF3 homolysis produces H2. The photophysical properties of 2 and 3 provide a rationale for the disparate light stability. [ABSTRACT FROM AUTHOR]

The first oxidative C(sp3)−H/C(sp3)−H cross-dehydrogenative coupling (CDC) reaction promoted by an internal oxidant is reported. This copper-catalyzed CDC reaction of oxime acetates and trifluoromethyl ketones provides a simple and efficient approach towards 2-trifluoromethyldihydropyrrol-2-ol derivatives in a highly diastereoselective manner by cascade C(sp3)−C(sp3) bond formation and cyclization. These products were further transformed into various significant and useful trifluoromethylated heterocyclic compounds, such as trifluoromethylated furan, thiophene, pyrrole, dihydropyridazine, and pyridazine derivatives. A trifluoromethylated analogue of an Aβ42 lowering agent was also synthesized smoothly. Preliminary mechanistic studies indicated that this reaction involves a copper(I)/copper(III) catalytic cycle with the oxime acetate acting as an internal oxidant. [ABSTRACT FROM AUTHOR]

We herein showcase the ability of NHC-coordinated dinuclear NiI-NiI complexes to override fundamental reactivity limits of mononuclear (NHC)Ni0 catalysts in cross-couplings. This is demonstrated with the development of a chemoselective trifluoromethylselenolation of aryl iodides catalyzed by a NiI dimer. A novel SeCF3-bridged NiI dimer was isolated and shown to selectively react with Ar−I bonds. Our computational and experimental reactivity data suggest dinuclear NiI catalysis to be operative. The corresponding Ni0 species, on the other hand, suffers from preferred reaction with the product, ArSeCF3, over productive cross-coupling and is hence inactive. [ABSTRACT FROM AUTHOR]

The reaction of (5-hydroxypentylthio magnesium porphyrazine) with 2-methoxy-4,6-bis(trifluoromethyl)benzoic acid in DCCI and PTSA, esterified MgPz having [5-thiopentyl 2-methoxy-4,6-bis(trifluoromethyl)benzoate] substituent was obtained. Further reactions of the metal-free porphyrazine with M2+(Mg, Co, Cu, Zn, Fe) acetates have produced the metallo-porphyrazines. Finally, by the reaction of FePzCl with pyridine or pyrazine compounds, [FePz(py)2] and [FePz(pyz)]ncomplexes were prepared as the novel stable complexes, respectively. The target compounds have been characterized by using different spectroscopic methods such as FT-IR, UV-Vis, mass,1H,13C, and19F NMR together with elemental analysis. The aggregation and the solubility features were indicated in various concentrations and solvents. [ABSTRACT FROM PUBLISHER]

Four new fully triphenylamine-based polyamides coded as polyamide (CF3,CF3), polyamide (CF3,CH3), polyamide (CH3,CF3), and polyamide (CH3,CH3) were synthesized by the phosphorylation polyamidation reaction from various combinations of 3,5-bis(trifluoromethyl)-4′,4″-dicarboxytriphenylamine, 3,5-dimethyl-4′,4″-dicarboxytriphenylamine, 3,5-bis(trifluoromethyl)-4′,4″-diaminotriphenylamine, and 3,5-dimethyl-4′,4″-diaminotriphenylamine. All the polyamides were amorphous and readily soluble in many common organic solvents and could be solution-cast into transparent, flexible, and strong films with good mechanical properties. They had useful levels of thermal stability associated with high glass-transition temperatures of 268–287°C and 10 wt%-loss temperatures in excess of 500°C. Cyclic voltammograms of the film of polyamide (CH3,CH3) on the indium-tin oxide-coated glass substrates exhibited two oxidation redox couples withE1/2around 0.82 and 1.29 V vs. Ag/AgCl in tetrabutylammonium perchlorate/acetonitrile solution, accompanied by a color change from pale yellow neutral state to dark green oxidized state. The CF3-substituted polyamides displayed a higher oxidation potential and less electrochemical stability as compared to the CH3-substituted analogues. [ABSTRACT FROM PUBLISHER]

A broadly applicable, practical, scalable, efficient and highly α- and enantioselective method for addition of a silyl-protected propargyl moiety to trifluoromethyl ketones has been developed. Reactions, promoted by 2.0 mol % of a catalyst that is derived in situ from a readily accessible aminophenol compound at ambient temperature, were complete after only 15 minutes at room temperature. The desired tertiary alcohols were isolated in up to 97 % yield and 98.5:1.5 enantiomeric ratio. Alkyl-, alkenyl-, alkynyl-, aryl- or heteroaryl-substituted trifluoromethyl ketones can be used. Utility is highlighted by application to a transformation that is relevant to enantioselective synthesis of BI 653048, a compound active against rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

A conceptually novel strategy with achiral pyridine as the ancillary ligand to stabilize high-valent copper species for the first asymmetric radical oxytrifluoromethylation of alkenes with alcohols under CuI/phosphoric acid dual-catalysis has been developed. The transformation features mild reaction conditions, a remarkably broad substrate scope and excellent functional group tolerance, offering an efficient approach to a wide range of trifluoromethyl-substituted tetrahydrofurans bearing an α-tertiary stereocenter with excellent enantioselectivity. Mechanistic studies support the presumed role of the achiral pyridine as a coordinative ligand on copper metal to stabilize the key transient reaction species involved in the asymmetric induction process. [ABSTRACT FROM AUTHOR]

We have developed a transition-metal free trifluoromethylation protocol between enamines and CF3SO2Na. A wide range of β-trifluoromethyl substituted enamines were delivered in moderate to high yields with only E-configurations. [ABSTRACT FROM AUTHOR]

Trifluoromethylthiolation and trifluoromethylselenolation of 3- or 4-iodo(bromo)-2-pyrones with (bpy)CuSCF 3 and [(bpy)CuSeCF 3 ] 2 provide a convenient method for the synthesis of trifluoromethylthio(seleno)lated 4-alkoxy-, aryloxy-, and benzyloxy-2-pyrones in high yields. [ABSTRACT FROM AUTHOR]

Ethyl α-nitro-β-trifluoromethyl acrylate was synthesized by nucleophile-catalyzed reaction of ethyl nitroacetate with excess trifluoroacetaldehyde methyl hemiacetal and subsequent dehydration of the intermediate alcohol with PO. The synthesized nitro olefin regioselectively reacts with the substituted indoles to give fluorinated 3-indolyl-2-nitrobutyrates, which were converted into the corresponding β-trifluoromethyl-substituted tryptophan analogs via the nitro group reduction followed by saponification of the ethoxycarbonyl group. In the step of synthesis of amino ester, the 2-methylindole derivative was resolved into diastereomers, which were transformed to the corresponding acids separately. It was found that the synthesized β-trifluoromethyltryptophans have plant-growth regulating activity apparently attributable to their metabolic transformations into substituted α-trifluoromethylindol-3-ylacetic acids. [ABSTRACT FROM AUTHOR]

Hydroxytrifluoromethylation of alkenes using the fluoroform (CF3H)-derived [CuCF3] reagent is described. In the presence of additive B2Pin2 and air, this reagent effectively facilitates the addition of hydroxy and trifluoromethyl groups across an alkene double bond, a formal hydroxytrifluoromethylation process. Various β-trifluoromethyl alcohols can be synthesized from simple alkenes where the ultimate CF3 source is the industrial byproduct fluoroform. [ABSTRACT FROM AUTHOR]

NMR and single crystal X-ray structure data for four structurally similar semicarbazones and thiosemicarbazones were compared. In solution, proton NMR showed considerable variation in their chemical shift values especially for the NH protons. In the case of the semicarbazones this peak appeared as a broad singlet with an integration ratio of two while for the thiosemicarbazones the amino group showed two distinct singlets with marked chemical shift differences. This is attributed to the differences in the canonical forms of the thiosemicarbazone amino group and the semicarbazone analogue. Additionally, we provide evidence that the 2-trifluoromethyl phenyl substituted semicarbazone ( 2) formed an intermolecular hydrogen bond with one of the hydrogens of the NH group while this was totally absent in the thiosemicarbazone. We explain this by the restricted rotation of the CN bond in the thiosemicarbazone due to its double bond character compared to the less restricted rotation in semicarbazone compound. Graphical Abstract: NMR and single crystal X-ray structure data for four structurally similar semicarbazones and thiosemicarbazones were compared for their hydrogen bonding characteristics. [ABSTRACT FROM AUTHOR]

Iridium-catalyzed aromatic borylation provides quick onestep access to 2,6-bis(trifluoromethyl)pyridine-4-boronic acid pinacol ester. Suzuki couplings of this highly electron-deficient pyridine-4-boronic ester with various (hetero)aryl bromides was successfully carried out and the coupled products were obtained in 46–95% isolated yields. Double and triple Suzuki couplings, with dibromo- and tribromoarenes, respectively, were also achieved. Thus demonstrating that this pyridine- 4-boronic ester can be a useful source for the installation of one of the strongest electron-withdrawing aromatic group in organic compounds. [ABSTRACT FROM AUTHOR]

As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study. The results showed that the differentiation effect of ATPR on APL cells was accompanied with autophagy induction and PML-RARα degradation via activating Notch1 signaling pathway. Moreover, inhibition of autophagy using 3-methyladenine (3-MA) or small interfering RNA (siRNA) that targets essential autophagy gene ATG5 abrogated the ATPR-induced cell differentiation. Furthermore, when pretreated with DAPT, a γ-secretase inhibitor, the Notch1 signaling pathway was blocked in APL cells, followed by the reduction of ATPR-induced autophagy and differentiation. Taken together, these results suggested that autophagy play an important role in ATPR-induced cell differentiation, which may provide a novel approach to cure APL patients. [ABSTRACT FROM AUTHOR]

Among bistable photochromic molecules, diarylethenes (DAEs) possess the distinct feature that upon photoisomerization they undergo a large modulation of their π-electronic system, accompanied by a marked shift of the HOMO/LUMO energies and hence oxidation/reduction potentials. The electronic modulation can be utilized to remote-control charge- as well as energy-transfer processes and it can be transduced to functional entities adjacent to the DAE core, thereby regulating their properties. In order to exploit such photoswitchable systems it is important to precisely adjust the absolute position of their HOMO and LUMO levels and to maximize the extent of the photoinduced shifts of these energy levels. Here, we present a comprehensive study detailing how variation of the substitution pattern of DAE compounds, in particular using strongly electron-accepting and chemically stable trifluoromethyl groups either in the periphery or at the reactive carbon atoms, allows for the precise tuning of frontier molecular orbital levels over a broad energy range and the generation of photoinduced shifts of more than 1 eV. Furthermore, the effect of different DAE architectures on the transduction of these shifts to an adjacent functional group is discussed. Whereas substitution in the periphery of the DAE motif has only minor implications on the photochemistry, trifluoromethylation at the reactive carbon atoms strongly disturbs the isomerization efficiency. However, this can be overcome by using a nonsymmetrical substitution pattern or by combination with donor groups, rendering the resulting photoswitches attractive candidates for the construction of remote-controlled functional systems. [ABSTRACT FROM AUTHOR]

A comprehensive survey of pathways leading to the generation of α-trifluoromethyl monocyclic piperidinic derivatives is provided (65 references). These compounds have been synthesized either from 6-membered rings e.g., pipecolic acid or lactam derivatives by introduction a trifluoromethyl group, from pyridine or pyridinone derivatives by reduction, and from 5-membered rings e.g., prolinol derivatives by ring expansion, from linear amines by cyclization or from dienes/dienophiles by [4 + 2]-cycloaddition. [ABSTRACT FROM AUTHOR]

A copper-mediated synthesis of 4-(trifluoromethyl)pyrazoles is described. In one step from readily accessible α,ß-alkynic tosylhydrazones, a remarkable domino sequence of cyclization, trifluoromethylation, and detosylation takes place to furnish the 4-CF3 N-H pyrazole cores with good functional group compatibility. The reaction conditions are mild and convenient, at room temperature in air, using the commercially available trifluoromethyltrimethylsilane (TMSCF3) as the CF3 source. The method can be applied to the synthesis of a 4-CF3 analogue of the anti-inflammatory drug celecoxib. [ABSTRACT FROM AUTHOR]

Room-temperature ionic liquids (RTILs) are an emerging class of electrolytes for supercapacitors. In this work, we investigate the effects of different supercapacitor models and anion shape on the electrical double layers (EDLs) of two different RTILs: 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Emim][Tf2N]) and 1-ethyl-3-methylimidazolium 2-(cyano)pyrrolide ([Emim][CNPyr]) bymolecular dynamics (MD) simulation. The EDLmicrostructure is represented by number densities of cations and anions, and the potential drop near neutral and charged electrodes reveal that the supercapacitor model with a single electrode has the same EDL structure as the model with two opposite electrodes. Nevertheless, the employment of the one-electrode model without tuning the bulk density of RTILs is more time-saving in contrast to the two-electrode one. With the one-electrode model, our simulation demonstrated that the shapes of anions significantly imposed effects on the microstructure of EDLs. The EDL differential capacitance vs. potential (C-V) curves of [Emim][CNPyr] electrolyte exhibit higher differential capacitance at positive potentials. The modeling study provides microscopic insight into the EDLs structure of RTILs with different anion shapes. [ABSTRACT FROM AUTHOR]

The protocol presented here is a new strategy for visible light induced C–H trifluoromethylation at C4 of benzimidazoles using Togni's reagent in the presence of fac-Ir(ppy)3. Its advantages are its operational simplicity, mild reaction conditions, low catalyst loading and wide substrate scope in which electron-withdrawing, electron-donating groups and different protecting groups are tolerated. [ABSTRACT FROM AUTHOR]

A method for the trifluoromethylation of orthohydroxycinnamic esters was developed to achieve the regioselective synthesis of 3-trifluoromethylated coumarins. The reaction was performed by using the Togni reagent as the CF3 source under mild conditions and showed good functionalgroup tolerance. The scope of this copper-mediated method was further expanded to the synthesis of 3-trifluoromethylated carbostyrils starting from ortho-aminocinnamic derivatives. Interestingly, a sequential one-pot synthesis of 3-trifluoromethylated coumarins starting from salicylaldehydes was further developed. The mechanism of this cascade reaction was explored, and a radical pathway was found to be consistent with the obtained results. [ABSTRACT FROM AUTHOR]

Among the fluorinated noncanonical amino acids, L-trifluoromethionine (TFM) and L-S-(trifluoromethyl)cysteine (TfmCys), fluorinated analogues of methionine and cysteine, are of particular interest because of their ability to locally increase the hydrophobicity of peptides. We report herein the synthesis of tert-butoxycarbonyl/benzyl-protected TFM and TfmCys by using a cheap and user-friendly radical trifluoromethylation approach. The benzyl protecting group of these fluorinated amino acids could be conveniently removed by hydrogenolysis, which circumvented troublesome saponification reactions. For the first time, TfmCys was inserted into a peptide sequence by liquidor solid-phase peptide synthesis. Finally, a late trifluoromethylation strategy with the use of Togni's reagent on disulfidebridged peptides was also efficient to incorporate TFM or TfmCys at both N-terminal and internal positions. [ABSTRACT FROM AUTHOR]

Condensation of fluorinated 1,3-dicarbonyl compounds with formaldehyde and l-amino acid ester hydrochlorides in acetate buffer, AcONa-AcOH (pH 5.9), at room temperature gave chiral hexahydropyrimidines, both containing and lacking a trifluoroacetyl group at position 5 of the heterocycle. In contrast, the reaction of ethyl 3-oxo-4,4,4-trifluorobutanoate with formaldehyde and ethyl (S)-tyrosinate hydrochloride under the same conditions gave a new chiral tetrahydropyrimidinium salt containing the trifluoroacetate anion in good yield. It is interesting that one of the formaldehyde molecules acts as an oxidant in this process. [ABSTRACT FROM AUTHOR]

Direct trifluoromethylation of organic molecules is of upmost importance in medicinal chemistry and agrochemical research. However, finding sustainable reaction conditions should be a priority for chemists to improve the applicability of their research. Herein, we highlight recent advances in transition-metal-free and photochemical activation of sodium triflinate, a commercially available and easy-to-handle source of CF3 radical. 1. Introduction 2. Transition-Metal-Free Activation of Sodium Triflinate 3. Photochemical Activation of Sodium Triflinate 4. Conclusions and Outlook [ABSTRACT FROM AUTHOR]

Synthetic methods for the preparation of compounds containing trifluoromethyl groups are in extremely high demand in nearly every sector of the chemical industry. Over the last several years the chemistry of N- tert-butylsulfinyl-3,3,3-trifluoroacetaldimine has undergone particular development. Currently, it is commonly used as a versatile reagent for general asymmetric synthesis of trifluoromethyl-containing amines and amino acids of pharmaceutical potential. This review provides a critical and comprehensive overview of synthetic applications of this reagent as well as of several relevant analogues, such as aldimines containing -CHF2, -CClF2, -CBrF2, and -CF2P(O)(OEt)2 groups and N- tert-butylsulfinyl-3,3,3-trifluoromethyl-substituted ketimines. Where it is possible, we emphasize the structural novelty and pharmaceutic value of the products obtainable by application of these reagents. [ABSTRACT FROM AUTHOR]

Two series of epoxy resins modified with trifluoromethyl-containing poly(amic acid)s and polyimides, respectively, were prepared. The effects of trifluoromethyl group and imide unit on the properties of epoxy resins were investigated. The epoxy resins modified with poly(amic acid)s exhibited better performance because poly(amic acid)s serve as amine curing agent in epoxy resins and form chemical bond with epoxy matrix, thus having higher miscibility with epoxy resin than the epoxy resins modified with polyimides. The glass transition temperatures of the modified epoxy resins were in the range of 88.9-168.2 °C. Compared with unmodified epoxy resin, the modified epoxy resins exhibited better thermal stability with char yield at 800 °C ranging from 18 to 55 %, lower hydrophilicity with water absorption in the range of 0.47-0.95 %, and water contact angle of 94.9-105.0°. The introduction of trifluoromethyl group decreases the surface free energy and hydrophilicity of the modified epoxy resins. The SEM images of the fracture surfaces of the modified epoxy resins showed tough fracture features, indicating the enhancement of toughness of these resins in which imide unit had been introduced. [ABSTRACT FROM AUTHOR]

Methods of synthesis of trifluoromethylfuryl derivatives of phosphonocarboxylic acids are studied. By addition of diethyl hydrogen phosphite to alkyl 3-(5-trifluoromethylfur-2-yl)acrylate under the conditions of the Pudovik reaction the corresponding derivative of 3-phosphonopropionic acid was prepared. Diethyl (5-trifluoromethylfur-2-yl)methanephosphonate in presence of potassium tert-butylate reacts with ethyl acrylate to form trifluoromethylfuryl derivative of 4-phosphonobutyric or 4-phosphonopimelic acid depending on the reaction conditions. In the products of reaction of the alkyl 3-(5-trifluoromethylfur-2-yl)-3-(diethoxyphosphoryl) propionate with ethyl acrylate in the presence of potassium tert-butylate formation of trifluoromethylfuryl derivative of the 3-phosphonoadipic acid is detected. 3-(5-Trifluoromethylfur-2-yl)-3-(diethoxyphosphoryl) propionic acid and its acid chloride are synthesized. The latter compound is used for acylation of glycine to form the corresponding N-acyl derivative. It is suggested that such compounds may be transported in the cell using usual channels of transportation of the amino acids and short peptides. [ABSTRACT FROM AUTHOR]

New rigid polyimides with bulky CF3 groups were synthesized and engineered into high-performance hollow fiber membranes. The enhanced rotational barrier provided by properly positioned CF3 side groups prohibited fiber transition layer collapse during cross-linking, thereby greatly improving CO2/CH4 separation performance compared to conventional materials for aggressive natural gas feeds. [ABSTRACT FROM AUTHOR]

A convenient, efficient, one-pot strategy for the synthesis of structurally diverse trifluoromethylated spirotetrahydropyridine-3-carboxylate derivatives is disclosed by taking advantage of a four-component reaction involving arylidene isoxazol-5-ones, aromatic aldehydes, ethyl 4,4,4-trifluoro-3-oxobutanoate and ammonium acetate. Additionally, a more consecutive approach to the same products is achieved via a one-pot, multicomponent reaction. The protocol allows easy access to trifluoromethylated spiroheterocycles in moderate to good yields under mild and catalyst-free conditions. [ABSTRACT FROM AUTHOR]

A novel phosphine-catalyzed, highly enantioselective umpolung addition of trifluoromethyl ketimines to Morita-Baylis-Hillman carbonates was developed and it provides facile access to optically active trifluoromethyl amines with a chiral tertiary stereocenter under mild reaction conditions. The salient features of this reaction include general substrate scope, mild reaction conditions, good yields, high enantioselectivity, ease of scale-up to gram scale, and further transformations of the products. [ABSTRACT FROM AUTHOR]

The reaction of 1-(trifluoromethyl)alkenes (CF3CH=CHR) with arylboroxines (ArBO)3 in the presence of a chiral diene-rhodium catalyst gave high yields of chiral 1,1-difluoroalkenes (CF2=CHC*HArR) with high enantioselectivity (≥95% ee). The reaction is assumed to proceed through μ-fluoride elimination of μ,μ,μ-trifluoroalkylrhodium intermediate that is generated by arylrhodation of the 1-(trifluoromethyl)alkene. [ABSTRACT FROM AUTHOR]

Trifluoromethylated iodoisoxazoles have been synthesized by the reaction of trifluoroacetohydroximoyl chloride, alkynes, and Niodosuccinimide in a one-pot reaction under metal-free and mild conditions. An array of iodoisoxazole compounds with a wide range of functionalities was obtained in moderate to good yields. The iodine-substituted isoxazoles render versatile reaction sites for subsequent conversion. Plausible pathways are proposed based on the control experiments. [ABSTRACT FROM AUTHOR]

In the presence of catalytic amounts of Cu(OAc)2, the hydroarylation of (trifluoromethyl)alkynes with arylboronic acids proceeded in MeOH at 28 °C to afford diverse β-(trifluoromethyl)styrenes. Moreover, the hydroalkenylation and hydroallylation of a (trifluoromethyl)alkyne using styryl- and allylboronates afforded trifluoromethylated 1,3- and 1,4-dienes. [ABSTRACT FROM AUTHOR]

Papain from Carica papaya demonstrated catalytic promiscuity was first discovered to catalyze the synthesis of trifluoromethyl carbinol derivatives via aldol reaction between α,α,α-trifluoromethyl ketones and aliphatic ketones in a mixed solvent of DMF and water. The best results of the corresponding aldol products with up to 99% yield and 30% ee were achieved. [ABSTRACT FROM AUTHOR]

The title compound, the 4-phenyl-6-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one (4) with chemical formula: (C16H12F3NO), was synthesized from N-[4-(trifluoromethyl)phenyl]cinnamamide (3), chemical formula: (C16H12F3NO), through an intramolecular cyclization mediated by triflic acid. Preliminary molecular characterization of both compounds was performed by Fourier transform infrared spectroscopy, gas chromatography mass spectrometry, and nuclear magnetic resonance spectroscopy (1H, 13C); crystallographic characterization was completed by X-ray diffraction of polycrystalline samples. The title compound 4 crystallized in a monoclinic system and unit-cell parameters are reported [a = 16.002 (3), b = 5.170 (1), c = 17.733 (3) Å, β = 111.11 (2)°, unit-cell volume V = 1368.5 (3) Å3, Z = 4] P21/c (No. 14) space group; the title compound 3 crystallized in a monoclinic system and unit-cell parameters are reported [a = 12.902 (2), b = 5.144 (1), c = 20.513 (5) Å, β = 91.67 (2)°, unit-cell volume V = 1360.7 (4) Å3, Z = 4] P21/c (No. 14) space group. [ABSTRACT FROM AUTHOR]

In the present investigation, a series of substituted hydroxytriazenes containing trifluoromethyl group were synthesized via diazocoupling reaction with phenylhydroxylamine. The structure of synthesized hydroxytriazenes has been assigned on the basis of elemental analysis, IR, H NMR and mass spectroscopy data. The lipid lowering effect of synthesized compounds was evaluated on triton-induced hyperlipidemia model in adult male Charles Foster rats. Administration of 400 mg/kg body wt. dose of triton WR 1339 causes elevation in total cholesterol, phospholipid, and triglyceride levels and inhibits post-heparin lipolytic activity, which was reversed by hydroxytriazenes. Adose of 100 mg/kg body wt. also inhibits free radical generation of superoxide anions and hydroxyl radicals and lipid oxidation. [ABSTRACT FROM AUTHOR]

The synthesis of mono-, di-, and trifluoromethyl aryl ethers by fluorodecarboxylation of the corresponding carboxylic acids is reported. AgF2 induces decarboxylation of aryloxydifluoroacetic acids, and AgF, either generated in situ or added separately, serves as a source of fluorine to generate the fluorodecarboxylation products. The addition of 2,6-difluoropyridine increased the reactivity of AgF2, thereby increasing the range of functional groups and electronic properties of the aryl groups that are tolerated. The reaction conditions used for the formation of trifluoromethyl aryl ethers also served to form difluoromethyl and monofluoromethyl aryl ethers. [ABSTRACT FROM AUTHOR]

Prostate cancer is a major cause of male death worldwide and the identification of new and improved treatments is constantly required. Among the available options, different non-steroidal androgen receptor (AR) antagonists are approved also to treat castration-resistant forms. Most of these drugs show limited application due to the development of resistant mutants of their biological target. Following docking-based studies on a homology model for the AR open antagonist conformation, a series of novel 3,5-bis-trifluoromethylphenyl compounds was designed with the aim to improve the antiproliferative activity of anti-androgen drugs bicalutamide and enzalutamide. The new structural modifications might impede the receptor to adopt its closed agonist conformation also in the presence of adaptive mutations. Among the novel compounds synthesised, several displayed significantly improved in vitro activity in comparison with the parent structures, with IC 50 values in the low micromolar range against four different prostate cancer cell lines (LNCaP, VCaP, DU-145, 22Rv1). Selected hits demonstrated full AR antagonistic behaviour and promising candidates for further development were identified. [ABSTRACT FROM AUTHOR]

The reaction of o-phenylenediamine with condensed 4 H-pyrans containing a trifluoroacetyl group at the β-position relative to the oxygen atom led to 2-(trifluoromethyl)chroman-2-ols and 3-(trifluoromethyl)-2,3-dihydro-1 H-benzo[ f]chromen-3-ols via a cascade process that was initiated by a Michael reaction. [ABSTRACT FROM AUTHOR]