Search

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]

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]

Methyl 2-aminothiophene-3-carboxylates were modified with trifluoromethyl-containing five-membered heterocycles by cyclocondensation of methyl trifluoropyruvate N-thiophen-2-ylimines with 1,3-N,N-binucleophiles (2-aminothiazoline and benzamidines) to obtain the corresponding 5-oxo-6-trifluoromethyl-2,3,5,6-tetrahydroimidazoles and 5-oxo-2-phenyl-4-trifluoromethyl-4,5-dihydro-1H-imidazoles. Radioligand binding was used to study the in fluence of the synthesized compounds on the neuronal NMDA receptors. [ABSTRACT FROM AUTHOR]

O and N centers of 3-trifluoromethyl-1,2-dihydroquinoxalin-2-one anion shows in reactions with haloalkanes an ambident nucleophilic character. The chemoselectivity of the reaction depends on the alkylating agent: the methylation of 3-trifluoromethyl-1,2-dihydroquinoxalin-2-one in acetonitrile in the presence of K2CO3 yields only an N-methyl isomer whereas under the same conditions in the reaction with (4-bromobutyl)-acetate О- and N-alkylations are competing. [ABSTRACT FROM AUTHOR]

The reactions of trifluoropyruvates with nitromethane and arylmagnesium bromides leading to trifluoromethyl-containing α-hydroxy acid esters were studied and various derivatives of the acids were obtained. [ABSTRACT FROM AUTHOR]

Abstract: A new protocol has been developed for the synthesis of α-trifluoromethyl ketones via organocatalyzed decarboxylative trifluoromethylation of β-ketoacids with Togni’s reagent. Among various simple amine catalysts, primary amines and secondary amines were identified to be more effective than tertiary amines, with piperazine being the most effective. Mechanistic investigations suggested that the primary or secondary amine-catalyzed reactions proceed mainly through trifluoromethylation of an enamine intermediate, which is more effective than the tertiary amine-catalyzed pathway that involves an enol intermediate. By using piperazine as the optimal organocatalyst, various β-ketoacids, including the sterically hindered α,α-disubstituted ones, were converted into the corresponding α-trifluoromethyl ketones in good yields. This research not only provides a useful strategy for the efficient synthesis of a wide range of α-trifluoromethyl ketones under mild conditions, but also constitutes one of the few studies on decarboxylative alkylation of β-ketoacids, which can intrigue further exploitation on organocatalyzed asymmetric decarboxylative alkylation reactions.Graphical Abstract: [ABSTRACT FROM AUTHOR]

A series of α-cyanostyrenes bearing anthracene and electron withdrawing trifluoromethyl units were designed and synthesized. The α-cyanostyrene skeleton favors aggregation induced enhanced emission behavior due to the restriction of intramolecular rotations. Remarkably, the anthryl cyanostyrenes bearing simple trifluoromethyl (CF3) substituents form stable organogels with enhanced fluorescence emission compared to their solution state. In water, the CF3 substituted anthrylstyrenes self-assemble into entangled fibrous nano/microstructures through intermolecular H-bonding, π–π stacking and cyano substituent interactions. The morphological features of the aggregates and the gels were substantiated using scanning electron microscopy, TEM, and powder XRD measurements. The stability of the gels was assessed using rheology investigations. [ABSTRACT FROM AUTHOR]

Extraction of microamounts of REE(III), U(VI), and Th(IV) with solutions of carbamoylmethylphosphine oxides (CMPOs) in organic diluents from aqueous HNO3 solutions containing lithium bis[(trifluoromethyl) sulfonyl]imide (LiTf2N) was studied. The efficiency of the REE(III), U(VI), and Th(IV) extraction from nitric acid solutions with CMPO solutions considerably increases in the presence of Tf2N- ions in the aqueous phase. The stoichiometry of the extractable complexes was determined, and the influence of the structure of the CMPO molecule, kind of organic diluent, and aqueous phase composition on the efficiency of the U(VI), Th(IV), and REE(III) extraction into the organic phase was considered. [ABSTRACT FROM AUTHOR]

The reaction of the divalent ruthenium complexes [CpFRuCl]n and [CpFRu(MeCN)3]PF6 with substituted pentafulvenes 1,2-(Me2NCH)(CO2Et)C5H3 and 1,3-(Me2NCH)(CO2Et)- C5H3 followed by hydrolysis affords new homoannular disubstituted ruthenocenes {1,2- (CO2Et)(CHO)C5H3}RuCpF and {1,3-(CO2Et)(CHO)C5H3}RuCpF (CpF = C5Me4CF3), re- spectively. [ABSTRACT FROM AUTHOR]

3,3,3-Trifluoropropene derivatives containing a sulfonyl, sulfoximine, or sulfamide substituent at position 1 were used in 1,3-dipolar cycloaddition reaction with ethyl cyanocarboxylate N-oxide generated by thermal decomposition of ethyl oximinochloroacetate, resulting in the formation of isomeric 4(5)-substituted ethyl 5(4)-(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylates and ethyl 4-(trifluoromethyl) isoxazole-3-carboxylate. [ABSTRACT FROM AUTHOR]

In addition to π-linkages and acceptors, the nature of donor moiety plays a vital role in tuning organic dye performance. Here, to assess the substitution effect of peripheral groups in donor moiety, two electron-donating and two electron-withdrawing groups are, respectively, introduced in the ullazine ring of JD21. It is shown that the introduction of trifluoromethyl group in JD-dye (JD21-CF) keeps the system to be of both the comparable light-harvesting and anti-aggregation ability to the original JD21 dye. It is regarded as a potentially efficient strategy to prepare JD-dyes or even other organic dyes. Additionally, the investigation on adsorbed dimeric dyes reveals that the electronic distribution with the highest occupied molecular orbital localizing on one dye molecule and the lowest unoccupied molecular orbital localizing on the TiO nanoparticle in the H-2-slip@TiO or F-2-slip@TiO configuration suggesting a weaker electronic coupling between two dyes. This type of adsorbed configuration with both dye dissociation is thus proposed to be dominant in an optimal solar cell based on the corresponding photoelectric characteristics. Our results clearly show a dependency of the dye performance on substituent groups. [ABSTRACT FROM AUTHOR]

The copper $$\hbox {CF}_{3}$$ or $$\hbox {SCF}_{3}$$ complexes as the fluoride sources for the synthesis of trifluoromethylated or trifluoromethylthiolated compounds are reviewed. Compared with the ordinary fluoride reagents, the addition of reactant species in the reaction systems of copper trifluoromethyl or trifluoromethylthio complexes were less, so the reaction systems are relatively simple and easy to operate. In most cases, the trifluoromethylated or trifluoromethylthiolated products were obtained in moderate to excellent yields. GRAPHICAL ABSTRACT: SYNOPSISThis mini-review highlights recent developments in trifluoromethylation or trifluoromethylthiolation using copper $$\hbox {CF}_{3}$$ or $$\hbox {SCF}_{3}$$ complexes, such as (phen) $$\hbox {CuCF}_{3}$$ , (phen) $$\hbox {Cu}(\hbox {CF}_{3})_{3}$$ , (bpy) $$\hbox {Cu}(\hbox {CF}_{3})_{3}$$ , $$(\hbox {Ph}_{3}\hbox {P})_{3}\hbox {CuCF}_{3}$$ , and (bpy) $$\hbox {CuSCF}_{3}$$ . [ABSTRACT FROM AUTHOR]

A series of 1,3-disubstituted imidazolium salts were synthesized through a convenient synthetic approach based on the reaction of 1,4-diazabuta-1,3-dienes with HClO. Their antitumor activity was evaluated in vitro against a number of human cancer cells. 1,3-Bis[(3,5-bis(trifluoromethyl)phenyl]imidazolium perchlorate turned out to be the most active against A549 and MCF-7 cancer cell lines with IC values of 5.24 and 4.21 μM, respectively. The results of structure-activity relationship study indicated that substituents on the imidazole derivatives play an important role in their cytotoxic activities. Finally, molecular docking of some tested compounds was carried out in order to investigate their binding pattern with the CDK2. [ABSTRACT FROM AUTHOR]

Metal complexes display functional interfaces for association with and stimulation of certain enzymes, that are liable to transfer genetic information in DNA for synthesis of specific proteins. Biological activity of five organotin carboxylates based on the ligand, 4-oxo-4-[3-(trifluoromethyl)phenylamino]butanoic acid, such as [BuSnL] ( 1), [PhSnL] ( 2), [MeSnL] ( 3), [BuSnL] ( 4), and [PhSnL] ( 5) have been synthesized and their biological activity as a function of substitution on the ligand was tested. Structure of the complexes was evaluated by elemental analysis, FT-IR and H, and C NMR spectra. FT-IR data and theoretical calculations revieled that the ligand acted as bidentate in complexes 1- 5. NMR data revealed four and six coordinated geometry of tin in solutions. The HOMO-LUMO study indicated thermodynamic stability of the complexes. AFM confirmed catalytic potential of the synthesized complexes. Biological screening showed that, with few exceptions, all the complexes exhibited significant activity against various bacterial and fungal strains. UV-Vis study confirmed that the ligand and its complexes binded to DNA via intercalative interactions. [ABSTRACT FROM AUTHOR]

Two novel isomeric fluorinated diamines were synthesized via Williamson etherification reaction. Their polymerization was carried out with commercially available anhydrides i.e., 3,3′,4,4′-Benzophenone tetracarboxylic dianhydride (BTDA), pyromellitic dianhydride (PMDA), 2,2-bis(3,4-dicarboxyphenyl) hexafluoropropanedianhydride (6FDA) and oxydipthalic anhydride (ODPA) respectively. A series of meta substituted fluorinated polyimides PD-11, PD-13, PD-14, PD-15 and ortho substituted fluorinated polyimides PD-41, PD-43, PD-44, and PD-45 were synthesized from each respective anhydride and diamine. FTIR confirmed the successful synthesis of polyimides with characteristic peaks. Solubility studies revealed comparable solubility attitude for meta and ortho substituted fluorinated polyimides, only PD-14 and PD-44 were soluble at room temperature. The other polyimides showed solubility at elevated temperatures in all solvents tested. The inherent viscosities of the polyimides also exhibited a descending order PD-43 > PD-11 > PD-45 > PD-44 > PD-14 > PD-41 > PD-13 > PD-15 that lies in the range of 0.372-0.875 dL/g respectively. X-ray diffraction (XRD) analysis premeditated the crystalline behavior of the polyimides. Furthermore thermal analysis i.e., thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) expressed enhanced thermal properties with meta-substituted fluorinated polyimides compared to their ortho-substituted analogues. Nonetheless, electrical recital of fluorinated polyimides was observed from moderate ( meta) to low ( ortho) dielectric constants values. Furthermore, the newly synthesized fluorinated polyimides demonstrated a low dielectric tangent loss and moisture absorption content. [ABSTRACT FROM AUTHOR]

A series of new fluorinated aromatic poly(ether imide)s (PEIs) were prepared from highly contorted 2,2′-bis(3,4-dicarboxyphenoxy)biphenyl dianhydride and various trifluoromethyl-containing bis(ether amine)s via chemical or thermal imidization. All the PEIs showed good solubility in a variety of organic solvents and could afford flexible, colorless, and transparent thin films via solution-casting. They showed cut-off wavelengths of Uv-vis absorptions below 380 nm and very low yellowness index ( b* < 7.0). They also showed high thermal stability with the 10% weight loss temperature from 503 to 585 °C of in nitrogen or air atmosphere. The glass transition temperatures ( T s) are recorded in the range of 194-254 °C by DSC. For a comparative study, another series of non-fluorinated PEIs derived from the same biphenyl-2,2′-diol bis(ether anhydride) with various bis(ether amine)s without the trifluoromethyl substituents were also synthesized and characterized. [ABSTRACT FROM AUTHOR]

Hydrochloric acid reacts with 5-ethyl-2-methallylsulfanyl-6-methylpyrimidin-4(3 H)-ones to protonate the nitrogen atom; it adds to the double bond of 2-prenylsulfanyl-6-(trifluoromethyl)pyrimidin-4(3 H)-one and gives the addition and heterocyclization products in the case of 2-prenylsulfanyl-6-methylpyrimidin-4(3 H)-one. [ABSTRACT FROM AUTHOR]

Multicomponent reactions of ethyl 1-trifluoromethyl-2-(trimethylsilyloxy)cyclopropanecarboxylate, isonitriles, and either 2-aminopyridine or amino acids provided imidazo[1,2- a]pyridines or γ-lactams, respectively. This access to trifluoromethyl-substituted heterocycles demonstrates again that siloxycyclopropanes can serve as hidden functionalized aldehydes and that this type of donor-acceptor-substituted cyclopropanes is particularly versatile. [ABSTRACT FROM AUTHOR]

New derivatives of the drug riluzole, 6-(trifluoromethoxy)benzothiazol-2-ylamine, modified at the endo- and exocyclic nitrogen atoms with trifluoromethyl-containing heterocycles were synthesized via transformations of methyltrifluoropyruvate and hexafluoroacetone N-6-(trifluoromethoxy)benzothiazol-2-ylimines by meams of cycloaddition and cyclocondensation reactions, respectively. The influence of the resulting compounds on neuronal NMDA receptors, as well as on the release and reuptake of the neurotransmitter glutamate was investigated. [ABSTRACT FROM AUTHOR]

The complex of copper(II) trifluoromethanesulfonate with chiral isopropyl bis(oxazoline) ligand (i-Pr-Box) was immobilized on accessible and inexpensive Merrifield resin according to a 'click' procedure. The resulting catalyst showed high efficiency and recyclability in the asymmetric Friedel-Crafts alkylation of indole and its derivatives. The catalyst can be recycled five times without appreciable loss in activity and enantioselectivity. [ABSTRACT FROM AUTHOR]

The article focuses on findings of a study on radical reactions of tricyclo[4.1.0.02]heptane and 1-Phenyltricyclo[4.1.0.0]heptane with trifluoromethyl (Phenylethynyl) Sulfone. Topics include interaction of tricycloheptanes with trifluoromethyl phenylethynyl sulfone, or triflone, under photochemical and thermal initiation; reaction of triflone with tricycloheptanes under conditions of radical initiation; and formation of norpinane products to the opening of the central carbon-carbon bond.

An improved procedure was developed for the synthesis of 3,3,3-trifluoro-1-nitropropene, and a new representative of gem-bromonitroalkenes, 1-bromo-3,3,3-trifluoro-1-nitropropene, was synthesized therefrom. Its reaction with phenyl azide gave a mixture of two regioisomeric 1,2,3-triazoles, from which pure 5-nitro-1-phenyl-4-(trifluoromethyl)-1 H-1,2,3-triazole was isolated. [ABSTRACT FROM AUTHOR]

A method is proposed for the synthesis of 3-nitro-2-phenyl-2-(trifluoromethyl)-2 H-chromenes by tandem condensation of salicylic aldehydes with ( E)-3,3,3-trifluoro-1-nitro-2-phenylprop-1-ene in the presence of triethylamine. The example of 3-nitro-2-phenyl-2-(trifluoromethyl)-2 H-chromene was used to demonstrate conjugated addition reactions with enamines, nitromethane, and aniline, which are characteristic for this class of compounds. The structure of the obtained products was confirmed by X-ray structural analysis. [ABSTRACT FROM AUTHOR]

The effect of HNO on the thermal stability and radiation resistance of trifluoromethyl phenyl sulfone (FS-13) used as extractant diluent in high-level waste partitioning was studied. Heating of FS-13 in the presence of 14 M HNO is not accompanied by exothermic effects up to 160°С. The amount of gaseous products released in the course of heating the system consisting of FS-13 and HNO and the composition of the major radiolysis products of the system components at irradiation doses of up to 0.5 MGy were determined. [ABSTRACT FROM AUTHOR]

A novel ionic liquid microemulsion composed of 1-octyl-3-methylimidazolium bis ((trifluoromethyl)sulfonyl)imide ([Omim]NTf, an ionic liquid), water, surfactant 1-hexadecyl-3-methylimidazolium bromide ([Cmim]Br, an ionic liquid), and cosurfactant n-butyl alcohol was prepared in our study. Pseudo-ternary phase diagram, conductivity measurement, and dynamic light scattering (DLS) analysis identified the microregion of microemulsion and confirmed the formation of water-in-ionic liquid (W/IL) region. Starch nanoparticles were prepared in the W/IL microemulsion with epichlorohydrin as cross-linker. Fourier transform infrared spectroscopy and X-ray diffraction characterized the structure of starch nanoparticles and demonstrated that cross-linking reaction happened among starch molecules. Scanning electron microscopy intuitively revealed that starch nanoparticles were spherical granules with smooth surface and fine dispersibility. Also, starch nanoparticles with a mean diameter of 93.2 nm and relatively concentrated size distribution were confirmed by DLS. [ABSTRACT FROM AUTHOR]

Three-component heterocyclizations of trifluoro- N-(prop-2-yn-1-yl)methanesulfonamide, trifluoro- N-pheny- N-(prop-2-yn-1-yl)methanesulfonamide, and trifluoro- N, N-di(prop-2-yn-1-yl)methanesulfonamide with formaldehyde and sodium azide afforded N-{[2-(hydroxymethyl)-2 H-1,2,3-triazol-4-yl]methyl}-, N-{[2-(hydroxymethyl)-2 H-1,2,3-triazol-4-yl]methyl}- N-phenyl-, and N, N-bis{[2-(hydroxymethyl)-2 H-1,2,3-triazol-4-yl]methyl}trifluoromethanesulfonamides as the major products together with minor 1-(hydroxymethyl)-1 H-1,2,3-triazole isomers. [ABSTRACT FROM AUTHOR]

Three diamine monomers with different derivatives of imidazole heterocyclic ring, aryl ethers and electron withdrawing trifluoromethyl groups in the backbone were synthesized and used in polycodensation reaction with various aliphatic and aromatic dicarboxylic acids for preparation of a series of novel polyamides (PAs). The PAs were obtained in high yields and possessed inherent viscosities in the range of 0.26-0.75 dL/g. All of the polymers were amorphous in nature, showed outstanding solubility and could be easily dissolved in amide-type polar aprotic solvents. They showed good thermal stability with glass transition temperatures between 162-302 °C. Thermogravimetric analysis showed that all polymers were stable, with 10% weight loss recorded above 421 °C in N atmospheres. All the PAs presented fluorescence upon irradiation with ultraviolet light and thus showed promise for applications in electroluminescent devices. The monomers and PAs were also screened for antibacterial activity against Gram positive and Gram negative bacteria. [ABSTRACT FROM AUTHOR]

Considering the increasing importance of fluorinated peptides, the development of efficient and reliable synthetic methods for the incorporation of unnatural fluorinated amino acids into peptides is a current matter of interest. In this study, we report the convenient Boc/benzyl and Cbz/ tert-butyl protection of both enantiomers of the quaternarized amino acid α-trifluoromethylalanine [( R)- and ( S)-α-Tfm-Ala]. Because of the deactivation of the nitrogen atom of this synthetic amino acid by the strong electron withdrawing trifluoromethyl group, the peptide coupling on this position is a challenge. In order to provide a robust synthetic methodology for the incorporation of enantiopure ( R)- and ( S)-α-trifluoromethylalanines into peptides, we report herein the preparation of dipeptides ready to use for solid phase peptide synthesis. The difficult peptide coupling on the nitrogen atom of the α-trifluoromethylalanines was performed in solution phase by means of highly electrophilic amino acid chlorides or mixed anhydrides. The synthetic effectiveness of this fluorinated dipeptide building block strategy is illustrated by the solid phase peptide synthesis (SPPS) of the Ac-Ala-Phe-( R)-α-Tfm-Ala-Ala-NH tetrapeptide. [ABSTRACT FROM AUTHOR]

Data on the biological activities of compounds containing m-dinitroaromatic ( m-DAr) moieties were presented and led to the conclusion that including this moiety in the structures of new biologically active compounds was promising. It was established that one nitro group in m-DAr could be replaced by trifluoromethyl without losing the biological activity of the obtained analogs. [ABSTRACT FROM AUTHOR]

This computational study investigates the photo-excitation process and subsequent photoproduct formation steps through non-radiative deactivation channels in open-chain conjugated N-substituted nitrone systems (model compounds of corresponding retinylnitrones) having electron-withdrawing groups on nitrogen. Calculations mostly based on CASSCF/6-31G* and CASMP2/6-31G* level of theories on a representative system with N-trifluoromethyl substituent have predicted initial photo-excitation to a planar singlet state. This photochemical path is subsequently followed by a barrierless non-radiative channel towards the lowest-energy conical intersection (CI) geometry having a terminal CNO kink, and situated at 30 kcal/mol below the planar excited state. Following the direction of its gradient difference (GD) vectors, an oxaziridine-type species (R =1.38 Å, R =1.53 Å, < CNO =55.8) appears at 3-6 kcal mol below the ground state nitrone system through a transition state (along its reverse direction of minimum-energy path), situated on the reaction pathway. This species with an elongated N-O bond seems to be heading towards an amide geometry. On the other hand, in the opposite GD vector direction a proper oxaziridine geometry has been obtained with a much shorter N-O bond distance (R =1.42 Å). [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A new trifluoromethyl-substituted bis(β-ketoimino)copper complex ( II) was synthesized and characterized by FTIR, elemental analysis, and X-ray diffraction (CIF file CCDC no. 1023178). XRD refinement revealed that the copper complex adopted a perfect central symmetric square planar structure with the copper center coordinated by two trans β-ketoimine ligands with delocalized double bonds. On activation with modified methylaluminoxane (MMAO), the bis(β-ketoimino)copper complex can polymerize methyl acrylate effectively. Introduction of trifluoromethyl group into the N-aryl ring of the ligands, which leads to strong electron-withdrawing effect, can improve significantly the catalytic activities. The activity of II/MMAO can reach 89.4 kg/mol Cu h, which is among the highest values reported for copper complexes in acrylic monomer polymerization. [ABSTRACT FROM AUTHOR]

1,1,1-Trifluoro-4-phenylbut-3-yn-2-one reacts with diphenyldiazomethane at 20°С in ethyl ether to afford 4-(trifluoromethyl)-1,1,6,6-tetraphenyl-4,6-dihydro-1 H-benz[5,6]oxepino[4,5- c]pyrazole. The process involves a stage of [3+2]-cycloaddition of the reagents, and the arising 3 H-pyrazole subsequently enters in an uncommon [3+6]-cycloaddition with 1 more molecule of diphenyldiazomethane. Further the formed diadduct of the initial acetylene suffers a 1,5-hydride shift and undergoes fragmentation with a loss of a nitrogen molecule thus converting into the final product. [ABSTRACT FROM AUTHOR]

Metal-catalyzed CH-functionalization of pyrrole and its derivatives via insertion of CF3-carbene generated from methyl 2-diazo-3,3,3-trifluoropropionate was studied. The reactions are completed within few minutes upon heating in toluene in the presence of 1 mol.% of commercially available copper trifluoroacetylacetonate. These reaction conditions allow simultaneous introduction of trifluoromethyl and methyl carboxylate groups into the aromatic pyrrole ring. Conditions for C(2)-selective monofunctionalization of NH-pyrroles were developed. [ABSTRACT FROM AUTHOR]

Amphiphilic substances, surfactants, are in common use to enhance the aqueous solubility of organic compounds. Solubilization of 3-{3,5-bis (trifluoromethyl)phenyl}quinoline was investigated by employing spectrophotometry, light scattering and tensiometry in micellar solutions of nonionic surfactants {dimethyldodecylamine-N-oxide, DDAO; polyoxyethylene(23)lauryl ether, Brij35; and polyoxyethylene(04)lauryl ether, Brij30}, a cationic surfactant (dodecyltrimethyl-ammonium bromide, DTAB), anionic surfactants (sodium dodecylbenzenesulfonate, SDBS; sodium dodecyl sulfate, SDS), and a zwitterionic surfactant (N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, DDAPS). It is noted that the solubility of the title compound 3-{3,5-bis (trifluoromethyl)phenyl}quinoline increased linearly with the increase in surfactant concentration irrespective of the type of surfactant. This is due to association of the title compound with surfactants. The molar solubilization ratio (MSR), micelle-water partition coefficient ( K), and the Gibbs energy of solubilization ( $$ \Delta G_{\text{S}}^{\text{o}} $$ ) of the title compound in the micelles were determined and correlated with each other. The nonionic surfactant DDAO showed the highest solubilization capacity. The order of degree of solubility among nonionic, cationic, and anionic surfactants for 3-{3,5-bis (trifluoromethyl)phenyl}quinoline is DDAO > DDAPS > SDBS > DTAB > SDS > Brij35 > Brij30. This comparative study can be used to select an appropriate medium for the title compound's solubilization, where the nonionic surfactants DDAO, Brij35 and Brij30 would be more beneficial due to their minimal protein binding and retention of their micellar form even after large dilution in blood owing to their very low critical micellar concentration values. The light scattering study indicated that the hydrodynamic radius of the blank and drug-loaded surfactants remained the same within experimental error. [ABSTRACT FROM AUTHOR]

In this work, stability experiments have been performed on a phenyl trifluoromethyl sulfone based solvent containing 6,6′-bis(5,6-dialkyl-[1,2,4-]triazin-3-yl)-2,2′-bipyridine and tri-butyl phosphate. This solvent is intended to be used in a grouped actinide extraction process for partitioning and transmutation purposes. The distribution ratio for americium was determined to approximately 20 and for europium approximately 0.26 giving a separation factor of 77. The solvent maintain good distribution ratios and separation factors during both gamma irradiation of 6.6 kGy h for up to 24 h and acid contact for up to 6 weeks at room temperature. [ABSTRACT FROM AUTHOR]

Amino acid transport is an attractive target for oncologic imaging. Despite a high demand of cancer cells for cationic amino acids, their potential as PET probes remains unexplored. Arginine, in particular, is involved in a number of biosynthetic pathways that significantly influence carcinogenesis and tumor biology. Cationic amino acids are transported by several cationic transport systems including, ATB (SLC6A14), which is upregulated in certain human cancers including cervical, colorectal and estrogen receptor-positive breast cancer. In this work, we report the synthesis and preliminary biological evaluation of a new cationic analog of the clinically used PET tumor imaging agent O-(2-[F]fluroethyl)- l-tyrosine ([F]FET), namely O-2((2-[F]fluoroethyl)methylamino)ethyltyrosine ([F]FEMAET). Reference compound and precursor were prepared by multi-step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [F]fluorination in 16-20 % decay-corrected yields with radiochemical purity >99 %. The new tracer showed good stability in vitro and in vivo. Cell uptake assays demonstrated that FEMAET and [F]FEMAET accumulate in prostate cancer (PC-3) and small cell lung cancer cells (NCI-H69), with an energy-dependent mechanism. Small animal PET imaging with NCI-H69 xenograft-bearing mice revealed good tumor visualization comparable to [F]FET and low brain uptake, indicating negligible transport across the blood-brain barrier. In conclusion, the non-natural cationic amino acid PET probe [F]FEMAET accumulates in cancer cells in vitro and in vivo with possible involvement of ATB. [ABSTRACT FROM AUTHOR]

Chiral ( R)-1-phenylethylamine was successfully employed in a tandem aza-Henry addition-reduction reaction to give chiral β-nitro α-trifluoromethyl amines. A subsequent coupling reaction with N-Boc-protected amino acids leads to obtain optically pure CF-modified dipeptides carrying two different N-protecting groups. These peptidomimetic units are characterized by the presence of the [CH(CF)NH] group as mimetic of the natural [CONH] peptidic bond and can be used for the synthesis of more complex CF-modified peptides after selective deprotection of one of the two amine functions. 2D NMR spectral analyses were employed to determine the absolute configurations of all newly synthesized chiral compounds. [ABSTRACT FROM AUTHOR]

A computational investigation of anomeric effects in piperidine rings bearing fluoro and trifluoromethyl substituents shows for both compounds the most pronounced evidence of the anomeric effect, as expressed as hyperconjugative delocalization of the nitrogen lone pair, in structures with the substituent in the axial position and the N-H bond in the equatorial position. This structure is the lowest-energy structure in the fluoro case but not in the trifluoromethyl case where there is an increased axial penalty associated with the CF group. The anomeric effect is characterized via geometrical evidence, natural bond orbital analysis, electrostatic effects, and energetic criteria. Computational results from a variety of levels of theory are presented including CCSD(T) with complete basis set extrapolation, B2PLYP-D, ωB97XD, B97-D, M06-2X, B3LYP, and MP2 allowing for a comparison of performance. The CCSD(T)/CBS results are very well represented by either B2PLYP-D or ωB97XD with moderate to large basis sets (aug-cc-pVTZ or aug-cc-pVDZ). Hyperconjugation, electrostatic effects, and steric effects play a role in the relative energetic ordering of the isomers considered. [ABSTRACT FROM AUTHOR]

FRET (Förster Resonance Energy Transfer) was applied to study structural properties of heparin-binding peptides containing the sequence XBBBXXBX where 'X' represents hydropathic or uncharged and 'B' represents basic amino acids. Internally quenched fluorogenic peptides were synthesized containing the fluorescent donor oaminobenzoic acid (o-Abz) and the acceptor dinitrophenyl ethylenediamine (Eddnp) group. Using the CONTIN computational package, distance distributions were recovered from time resolved fluorescence data, associated to end-to-end distances of the peptides. The peptides containing three or four repeat units have random structure in aqueous medium, and the interaction with low molecular weight heparin stabilized short end-to end distances. Experiments in water/trifluoroethanol (TFE) mixtures showed changes in distance distributions compatible with compact conformations stabilized above 40 % volume content of TFE in the mixture. Similar changes in distance distributions were also observed for the peptides in interaction with SDS micelles in aqueous suspensions and circular dichroism data revealed alpha-helix formation in the peptides in interaction with heparin, SDS micelles or the co-solvent TFE. The process is dependent on electrostatic and hydrogen bond interactions and the end-to-end distances obtained are smaller than expected for the peptides in linear α-helix conformation, indicating the occurrence of structural arrangements leading to additional decrease in the distances. [ABSTRACT FROM AUTHOR]

Phospholipase A of the bacterial outer membrane (OMPLA) is a β-barrel membrane protein which is activated under various stress conditions. The current study examines interaction of inhibitors of eucaryotic phospholipases A-palmitoyl trifluoromethyl ketone (PACOCF) and aristolochic acid (AA)-with OMPLA and considers a possible involvement of the enzyme in the Ca-dependent permeabilization of the outer membrane of Escherichia coli. Using the method of molecular docking, it has been predicted that PACOCF and AA bind to OMPLA at the same site and with the same affinity as the OMPLA inhibitors, hexadecanesulfonylfluoride and bromophenacyl bromide, and the substrate of the enzyme palmitoyl oleoyl phosphatidylethanolamine. It has also been shown that PACOCF, AA, and bromophenacyl bromide inhibit the Ca-induced temperature-dependent changes in the permeability of the bacterial membrane for the fluorescent probe propidium iodide and suppressed the transformation of E. coli cells with plasmid DNA induced by Ca and heat shock. The cell viability was not affected by the eucaryotic phospholipases A inhibitors. The study discusses a possible involvement of OMPLA in the mechanisms of bacterial transmembrane transport based on the permeabilization of the bacterial outer membrane. [ABSTRACT FROM AUTHOR]

The effect on heats of formation, of conjoined or proximate functional groups which can interact via polar or resonance effects, is examined using the –CF 3 group as a standard. Two metrics are applied: the difference in heat of formation of G–CF 3 and G–CH 3, where –G is a wide range of functional groups, and also the deviation of the heat of formation of G–CF 3 from the average of the heats of formation of G–G and CF 3–CF 3. This latter metric reveals both stabilizing and destabilizing effects on the heat of formation, of up to 60 kcal/mol, depending on the polar and resonance nature of the –G structure. The possibility of using such metrics as a correction the group additivity values is examined. [ABSTRACT FROM AUTHOR]

A method for the cyclization of hexafluoroacetone N-phenylimine derivatives with the formation of benzodiazepine analogs containing trifluromethyl groups has been elaborated. The obtained compounds were characterized by the NMR and mass spectral analysis and by the data from X-ray structural analysis. [ABSTRACT FROM AUTHOR]

The electrooxidation of a (∼3: 1) mixture of trifluoroacetic and 10-undecylenic acids in MeCN with an aqueous KOH addition on different anodic catalysts was studied. The oxidation of trifluoroacetate ions that forms trifluoromethyl radicals is the key stage of the process, while 10-undecylenic acid seems to be merely an acceptor of the electrogenerated radicals, i.e., shows the chemical properties characteristic of olefins. The galvanostatic electrolysis of trifluoroacetic and 10-undecylenic acids led to a mixture of the products of trifluoromethylation of the latter and the products of coupling of the formed radical species. According to a qualitative estimation, the total yield of these products was 74%. [ABSTRACT FROM AUTHOR]

Two new para-linked diether-diamines, bis(4-(4-amino-2-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy) phenyl)methanone and bis(4-(4-amino-2-(4,5-diphenyl-1H-imidazol-2-yl)phenoxy) phenyl)hexafluoropropane, bearing two ortho-linked phenyl-substituted imidazole pendants and trifluoromethyl groups were synthesized by the nucleophilic chlorodisplacement reaction of the synthesized 2-(2-chloro-5-nitrophenyl)-4,5-diphenyl-1H-imidazole with 4,4′-dihydroxybenzophenone or 4,4′-(hexafluoroisopropylidene)diphenol in refluxing DMAc in the presence of potassium carbonate. These diamines were utilized to prepare a series of novel poly(amide-ether)s (PAEs) via direct phosphorylation polycondensation with aliphatic and aromatic dicarboxylic acids. The polymeric samples were readily soluble in a variety of organic solvents and formed low-colored and flexible thin films via solution casting. These polymers showed glass-transition temperatures ( Ts) between 204 and 308 °C. Thermal behaviors of the PAEs were characterized by thermogravimetric analysis, and the 10 % weight loss temperatures were found to be in the range of 330-450 °C in N. The PAEs exhibited fluorescence emission in solution and in solid state with maxima around 423-494 nm and with the quantum yields in the range of 6-28 %. [ABSTRACT FROM AUTHOR]

The reactions of acetone, 2,2,2-trifluoroacetone and hexafluoroacetone in methanesulfonic (MSA) and triflic acids (TFSA) with benzene have been studied at M06-2X/6-311+G(d,p) level using cluster-continuum model, where the carbonyl group is explicitly solvated by acid molecules. The introduction of a trifluoromethyl group into the ketone structure reduces the activation energy of the tetrahedral intermediates formation due to an increase of the electrophilicity of the carbonyl group and raises the activation and the reaction energies of the C-O bond cleavage in formed carbinol due to the destabilization of the corresponding carbocation. The introduction of the second trifluoromethyl group inhibits the hydroxyalkylation reaction due to a very strong increase of the reaction and activation energies of the C-O bond cleavage which becomes the rate determining step. The most important catalytic effect of TFSA compared to MSA is not the protonation of the ketone carbonyl, but the reduction of the activation and reaction energies of the carbinol C-O bond cleavage due to better protosolvation properties. Even for TFSA no complete proton transfer to carbonyl oxygen has been observed for free ketones. Therefore, the protonation energies of free ketones cannot be considered as a measure of ketone reactivity in the hydroxyalkylation reaction. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Peaks of C(CF) doubly charged negative ions ( n = 6-12) have been observed in the mass spectra of the resonance electron capture by trifluoromethylfullerene C(CF) molecules. It has been established that these ions are formed owing to the attachment of two free isoenergetic electrons. The autodetachment of an extra electron has been detected for the doubly charged molecular ions ( n = 12). It has been established from the observation of the delayed fragmentation of the most abundant ions with n = 8 and 10 that the doubly charged negative ions, like their singly charged analogs, are metastable with respect to the separation of the CF fragment(s). The yield of doubly charged negative ions has been obtained as a function of the electron energy. By comparing them with the analogous dependences for the singly charged ions, the specific features have been revealed which were associated with the presence of the repulsive Coulomb barrier and the regular effect of the doubled energy of two additional electrons on the energy dependence of the dissociative decay of the doubly charged negative ions. The absolute cross section for the formation of the C(CF) ions has been measured. At the energy of their yield maximum near the 5 eV, it is ∼1 × 10 cm. [ABSTRACT FROM AUTHOR]

N-Benzyloxycarbonyl-2,2,2-trifluoroacetimidoyl chloride reacted with pyridin-2-amine derivatives to form substituted 2-trifluoromethyl-4 H-pyrido[1,2- a][1,3,5]triazin-4-ones. [ABSTRACT FROM AUTHOR]

From extraction experiments and γ-activity measurements, the exchange extraction constants corresponding to the general equilibrium M (aq) + 1·Na (org) $$ \Leftrightarrow $$ 1·M (org) + Na (aq) taking place in the two-phase water-phenyltrifluoromethyl sulfone (abbrev. FS 13) system (M = Li, HO, NH, Ag, Tl, K, Rb, Cs; 1 = benzo-18-crown-6; aq = aqueous phase, org = FS 13 phase) were evaluated. Further, the stability constants of the 1·M complexes in FS 13 saturated with water were calculated; they were found to increase in the series of $$ {\text{Cs}}^{ + } \, < \,{\text{Rb}}^{ + } \, < \,{\text{H}}_{ 3} {\text{O}}^{ + } \, < \,{\text{Ag}}^{ + } \, < \,{\text{Li}}^{ + } \, < \,{\text{NH}}_{4}^{ + } \, < \,{\text{K}}^{ + } \, < \,{\text{Tl}}^{ + } $$. [ABSTRACT FROM AUTHOR]

We study the creation of fluorescence patterns inside a gelatin gel by way of two-photon photoactivation of 7-azido-4-trifluoromethyl-1,2-benzopyrone (azidocomarin 151) contained in the gel matrix. As ultrafast light pulses are focused into the gel, onset of two-photon fluorescence, highly nonlinear in the applied optical power, is observed as azidocoumarin is converted into a fluorescent dye that binds to the gelatin. We fit the time dependence of the fluorescence to a model that incorporates the competition between coumarin photoactivation and photobleaching as well as the gradual degradation of the gel when it is exposed to the high intensity laser light. The model predicts that the initial rate of fluorescence onset should scale as the P, where P is laser power, while the signal at long exposure time should scale as P. The observed exponents are 4.18 and 1.34, respectively. The model allows us to estimate the cross section and quantum yield of two-photon induced photobleaching of azidocoumarin 151. The numerous technical uses of gelatin and the collagen from which it derives in areas ranging from photography to tissue engineering provide possible applications for the techniques described in this paper. [ABSTRACT FROM AUTHOR]

Two new aliphatic diamine monomers, one containing cyclohexane moiety and the other containing both cyclohexane and trifluoromethyl moieties, were synthesized. Two series of semi-aromatic polyimides (PIs) derived from the two diamines were prepared by one-step solution polycondensation using m-cresol as solvent. These PIs had inherent viscosities between 0.32 and 1.20 dL/g and could be processed to colorless, flexible and tough films. Compared with the PIs without trifluoromethyl group, the PIs with trifluoromethyl group showed better solubility in many solvents such as DMAc, NMP and m-cresol. It was also found that all the PI films had high optical transparency in the visible region with the cut-off wavelength of 291-379 nm. However, compared with the non-fluorinated PI 5 series, the PI 4 series showed lighter color. Furthermore, thermal analysis showed that the synthesized PIs had 5 % weight lost temperature ( T) in N of 372-425 °C, and the glass transition temperature ( T) of 221-270 °C. Moreover, all the PIs showed good mechanical properties with the tensile strengths of 80-114 MPa, tensile moduli of 2.7-3.5 GPa, and elongation at breaks of 5.1-26.5 %. [ABSTRACT FROM AUTHOR]