Visible-light-enabled multicomponent synthesis of trifluoromethylated 3-indolequinoxalin-2(1H)-ones without external photocatalysis

A novel and sustainable visible-light-enabled multicomponent reaction involving quinoxalin-2(1H)-ones,indoles,and CF3SO2Na that does not require an external photocatalyst is described.This photoinduced reaction employs air as the sole oxidant,thereby providing a green and highly step-efficient approach to a series of biologically important trifluoromethylated 3-indolequinoxalin-2(1H)-ones.

Copper-Promoted Conversion of Aromatic Amines into Trifluoromethylated Arenes： One-Pot Sandmeyer Trifluoromethylation

A simple copper-promoted one-pot Sandmeyer trifluoromethylation of aromatic amines with Langlois＇ reagent has been demonstrated. The reaction is performed in mild reaction conditions under an air atmosphere with good substrate scope and functional group compatibility. It provides an alternative and straightforward synthetic approach to access a variety of trifluoromethylated arenes.

Synthesis of 4-Trifluoromethylated 1,3-Butadienes via Palladium Catalyzed Heck Reaction

1,3-Butadiene plays a key role in modern synthetic chemistry and biochemistry because it is a key intermediate in the synthesis of many drugs.A new and effective method for the synthesis of 4-trifluoromethylated 1,3-butadiene through the fluorinated Heck reaction catalyzed by Pd(0)is described.Without additives,1-chloro-3,3,3-trifluoropropene(an inexpensive CF3 structural unit that is harmless to ozone)reacts with enamide to synthesize 4-trifluoromethylated 1,3-butadienes with good yield,high regioselectivity and chemical selectivity,and strong tolerance of substrate functional groups such as alkynes,aldehyde,and ester groups.

Ligand-Promoted,Enantioconvergent Synthesis of Aliphatic Alkanes Bearing Trifluoromethylated Stereocenters via Hydrotrifluoroalkylation of Unactivated Alkenes

While drug chirality remains one of the most important themes in medicinal chemistry and fluorine-containing drugs have comprised large portion of global pharmaceutical market,the synthesis of fluorine-containing compounds featuring a trifluoromethylated stereogenic carbon center is still underdeveloped.Recent strategy of enantioconvergent cross-coupling of trifluoromethylated alkyl halide has significantly updated previous toolbox that is dependent on additional functional group to achieve desired bond formation and highly enantioselective control.However,evident limitations were present in specific coupling candidate(sp?carbon)and/or prerequisite heteroatom in trifluoroalkyl source for inducing effective stereoconvergent differentiation.Leveraging novel design of sterically hindered bisoxazoline ligand and drastic increase of molecular complexity of in situ generated sp3 coupling partner via metal-hydride atom transfer,herein,we report a nickel-catalyzed,highly enantioselective hydrotrifluoroalkylation of unactivated alkenes for diverse synthesis of enantioenriched aliphatic alkanes featuring trifluoromehylated stereogenic carbon.Excellent stereochemical control(mostly>95:5 er),high catalytic reactivity,mild conditions,and broad substrate scope(40+examples),enable convenient late-stage asymmetric trifluoroalkylation of various biologically active complexmolecules.

Study on potassium bromodifluoroacetate Convenient approaches to the syntheses of trifluoromethylated compounds

Treatment of potassium bromodifluoroacetate(1)with alkyl halides in the presence of copper,iodide and potassium fluoride in DMF at 85—90℃ for 3—5h gavethe trifluoromethylated derivatives in moderate to high yields.

Regioselective electrochemical radical cascade cyclization of internal alkynes to selenated and trifluoromethylated dihydropyran

Dihydropyran(DHP)compounds are not only found in natural products and bioactive molecules,but also serve as important precursors in organic synthesis.Nonetheless,traditional methods for the construction of such compounds are usually limited to disubstituted DHPs.To address this synthetic challenge,reported here is an efficient electrochemical strategy toward the selenated and trifluoromethylated DHP compounds.The reaction proceeded smoothly under mild electrolysis conditions.The broad substrate scope(>50 examples)and scalable synthesis demonstrated the complexity-building potential of the strategy.Initial mechanistic studies reveal that cyclization may involve a radical process.This protocol may promote the further development of diversified synthesis of multi-substituted dihydropyran.

吡唑化合物pyr3干预对压力负荷诱导的大鼠左心室肥厚的影响

目的：探讨瞬时受体电位通道C亚族3亚型（TRPC3）的选择性阻滞剂吡唑化合物Ethyl-1-（4-f2，3，3一trichloroacrylamide）phenyl）-5-（trifluoromethyl）-1H—pyrazole-4-carboxylate（pyr3）的体内干预对压力负荷大鼠左心室肥厚（LvH）程度的影响。方法：采用腹主动脉缩窄手术建立左心压力负荷模型。30只200—240g雄性SD大鼠随机分为五组（n=6）：假手术对照组、手术对照组、假手术后全程给药组、手术后后期给药组，手术后全程给药组。6周后，计算各组大鼠左心室质量指数、左心室心肌细胞横径，逆转录多聚酶连反应（RT—PCR）、免疫组织化学和蛋白免疫印迹检测TRPC3和钙调神经磷酸酶A13信使核糖核酸（mRNA）和蛋白的表达水平。结果：与假手术对照组相比，手术对照组左心室肥厚相关指标（左心室质量指数和左心室心肌细胞横径）及TRPC3、钙调神经磷酸酶AB蛋白和mRNA的表达显著升高；假手术后全程给药组左心室肥厚相关指标无显著变化，而TRPC3和钙调神经磷酸酶AB蛋白及mRNA的表达量显著升高，差异均有统计学意义（P均〈0．05）。与手术对照组比较，手术后全程给药组左心室肥厚相关指标、TRPC3及钙调神经磷酸酶A13蛋白和mRNA表达均明显降低（P均〈0．05）；手术后后期给药组左心室肥厚相关指标及钙调神经磷酸酶AB蛋白和mRNA的表达下降，差异均有统计学意义（P均〈0．05），而TRPC3的蛋白和mRNA表达未见显著降低。结论：pyr3体内干预能够一定程度上阻止压力负荷导致的大鼠左心室肥厚，降低压力负荷大鼠左心室TRPC3和钙调神经磷酸酶AB表达的上调。

Synthesis and characterization of mixing soft-segmented waterborne polyurethane polymer electrolyte with room temperature ionic liquid

Composite polymer electrolytes based on mixing soft-segment waterborne polyurethane （WPU） and 1-butyl-3-methylimidazolium bis[（trifluoromethyl）sulfonyl]imide （BMImTFSI） have been prepared and characterized. The addition of BMImTFSI results in an increase of the ionic conductivity. At high BMImTFSI concentration （BMImTFSI/WPU = 3 in weight ratio）, the ionic conductivity reaches 4.27 × 10^-3 S/cm at 30 ℃. These composite polymer electrolytes exhibit good thermal and electrochemical stability, which are high enough to be applied in lithium batteries.

Synthesis, Crystal Structure and DNA-Binding Property of a Mn(Ⅱ) Complex Based on 5-(Tri-fluoromethyl)pyridine-2-carboxylic Acid

A new complex Mn(Htpc)2(H2O)2(1, Htpc = 5-(trifluoromethyl)pyridine-2-carboxylic acid) has been synthesized and characterized by elemental analysis, IR, TG and single-crystal X-ray diffraction. 1 belongs to triclinic system, space group P■ with a = 5.0885(10), b = 6.5574(13), c = 14.016(3) ?, β = 90.67(3)o, V = 436.34(17) ?3, Z = 1, Dc = 1.793 g·cm-3, μ = 0.855 mm-1, Mr = 471.18, F(000) = 235, the final R = 0.0454 and wR = 0.1134 for 1998 observed reflections with I > 2σ(I). The Mn(Ⅱ) ion is coordinated by two N and two O atoms from two Htpc as well as two O atoms from two coordinated water molecules, forming a 0D motif with distorted octahedral coordinate geometry. The adjacent 0D units are linked into 1D chains through hydrogen bond O(1W)–H(1 WB)···O(2), and via the O(1 W)–H(1 WA)···O(1) hydrogen bond the neighboring 1D chains are connected into a 2D supramolecular layer. Moreover, the interactions between the ligand and its complex with CT-DNA were studied by EtBr fluorescence probe, which suggested that these compounds bind to CT-DNA through an intercalation mode. The binding constants were 0.41 and 0.64 for Htpc and complex 1, respectively. It indicates that the interaction between complex 1 and CT-DNA is stronger than Htpc.

Asymmetric Bioreduction of 3,5-Bis（trifluoromethyl） Acetophenone to Its Corresponding Alcohol by Candida troplcalis

(S)-3,5-bistrifluoromethylphenyl ethanol is a key chiral intermediate for the synthesis of NK-1 receptor antagonists. Enantioselective synthesis of (S)-3,5-bistrifluoromethylphenyl ethanol was successfully performed in high enantiomeric excess (e.e.) through asymmetric reduction of 3,5-bis(trifluoromethyl) acetophenone catalyzed by Candida tropicalis 104 cells. The influence of some key reaction parameters such as substrate concentration, co-substrate and its concentration, biomass and reaction time was examined, respectively. The results showed that these factors obviously influence the yield, but the optical purity of the prepared product remains intact. The opti-mum conditions for the preparation of (S)-3,5-bistrifluoromethylphenyl ethanol were found to be as follows: sub-strate concentration 50 mmol?L?1; 50 g·L-1 of maltose as co-substrate; wet cell concentration 300 g·L-1; reaction for 30 h. Under above optimal conditions, the maximum yield for (S)-3,5-bistrifluoromethylphenyl ethanol reached 70.3% with 100% of product e.e.

Synthesis, Crystal Structure, and Biological Activity of 4-Chlorobenzaldehyde (2-trifluoromethylTrifluoromethyl-5,6,7,8-tetrahydrobenzo[4 ,5]-thieno[2,3-d]pyrimidin-4-yl)hydrazone Monohydrate

The novel title compound 4-chlorobenzaldehyde （2-trifluoromethyl-5,6,7,8- tetrahydro- benzo[4,5]thieno[2,3-d]pyrimidin-4-yl）hydrazone monohydrate （C18H14C1F3N4S.H20, Mr = 428.86） has been synthesized by a condensation reaction of 4-chlorobenzaldehyde with （2-trifuoromethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl）hydrazine, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21/c with a = 7.4252（7）, b = 26.344（2）, c = 10.3095（9） A, /3 = 109.407（2）~, V= 1902.0（3） A3, Z = 4, Dc = 1.498 g/cm^3, p = 0.356 mm-1, F（000） = 880, the final R = 0.0564 and wR = 0.1681 for 2343 observed reflections with I 〉 2o（/）. X-ray diffraction analysis reveals that the title hydrazone molecule is nearly planar except for the cyclohexene and trifluoromethyl moieties. In the crystal packing, the molecules form stacks by a three-dimensional framework, which results from intermolecular N（3）-H（3）...O（1）, O（1）-H（1B）...N（2）, O（1）- H（1B）...N（4） and O（1）-H（1A）...F（1） hydrogen bonds via water molecules together with π-π stacking interactions. Molecular geometry of the title compound in the ground state optimized by B3LYP functional with 6-311G＊＊ basis sets indicates that the calculations are in agreement with the experimental data. The preliminary bioassay suggested that the title compound exhibits relatively good fungicidal activity against Fusarium oxysporium fsp.vasinfectum and Dothiorella gregaria.

Syntheses, Crystal Structures, and Antitumor Activities of Two 2-Trifluoromethyl-5,6,7,8-tetrahydrobenzo[4,5]-thieno[2,3-d]pyrimidin-4-amine Derivatives

Two novel 2-trifluoromethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two appropriate amines with 4-chloro-2-(trifluoromethyl)-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidine, which started from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile, trifluoroacetic acid(TFA) and phosphorous oxychloride by one-pot procedure. Their structures were determined by single-crystal X-ray diffraction. Compound 1, N-(furan-2-ylmethyl)-2-trifluoromethyl-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4-amine, crystallizes in the monoclinic system, space group C2/c with a = 26.352(3), b = 7.5991(8), c = 17.1423(18) A, β = 114.667(2)°, V = 3119.5(6) A3 and Z = 8. Compound 2, N-(3-silatranylpropyl)-2-trifluoromethyl-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4-amine, crystallizes in the monoclinic system, space group P21/n with a = 13.4394(13), b = 8.9446(9), c = 18.9657(18) A, β = 101.9640(10)°, V = 2230.3(4) A3 and Z = 4. The preliminary bioassay indicated that compound 2 exhibits more potent antitumor activity against BCG-823 than 5-fluorouracil(5-FU).

Synthesis, Crystal Structure, and Antitumor Activity of 1-(4-Methoxybenzylidene)-2-(1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)hydrazine Monohydrate

The novel title compound 1-（4-methoxybenzylidene）-2-（1-phenyl-6-trifluoromethyl- 1H-pyrazolo[3,4-d]pyrimidin-4-yl）hydrazine monohydrate （C20HisF3N60-H20, Mr = 430.40） has been synthesized by a four-step procedure including the cyclization, chlorination, hydrazinolysis and condensation reaction, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to orthorhombic, space groupPbca with a = 8.3779（13）, b = 17.607（3）, c = 26.774（4） A, V= 3949.2（11） A3, Z=8, Dc = 1.448 g/cm3, μ = 0.117 mm-l, F（000） = 1776, the final R = 0.0553 and wR = 0.1516 for 2354 observed reflections with 1 〉 2σ（/）. X-ray diffraction analysis reveals that the title compound is almost coplanar except for the trifluoromethyl and phenyl moieties. In the crystal packing, the molecules are linked by intermolecular O（lW）-H（1WA）-＂N（2）, O（1W）-H（1WA）.--N（4） and N（5）-H（5A）...O（lW） hydrogen bonds via water molecules and stacked through π-π stacking interactions. The preliminary bioassay suggested that the title compound exhibits relatively good antitumor activity against HepG2 and BCG-823.

SYNTHESIS AND CHARACTERIZATION OF ORGANO-SOLUBLE FLUORINATED POLYIMIDES FROM 4,4'-BIS(3-AMINO-5-TRIFLUOROMETHYLPHENOXY)-BIPHENYL AND VARIOUS AROMATIC DIANHYDRIDES

An aromatic diamine monomer,4,4'-bis(3-amino-5-trifluoromethyl phenoxy)-biphenyl (TFBPDA),wassynthesized via the nucleophilic displacement reaction of 3,5-dinitrobenzotrifluoride and 4,4'-biphenol.The monomer wasreacted with various aromatic dianhydrides via the high temperature polycondensation procedure to provide a series ofpolyimides.The polyimides,PI-1 to PI-4,show good solubility not only in aprotic solvents,such as N-methyl-2-pyrrolidinone and N,N-dimethylacetamide,but also in many common solvents,such as m-cresol,chloroform andcyclopentanone.PI-4,derived from 4,4'-(hexafluoroisopropylidene)diphthalic anhydride and TFBPDA,was even soluble intoluene.Moreover,PI films exhibit good thermal stability,outstanding transparency in the visible light region and acceptablemechanical and electrical properties.The excellent combined properties of the polyimides make them as a good candidate forfabricating microelectronics.

Trifluoromethylation of Carbonyl Compounds with Sodium Trifluoroacetate

In the presence of copper （I） halide as catalyst, a variety of carbonyl compounds could be trifluoromethylated with sodium trifluoroacetate to give the corresponding alcohols in moderate to high yields.

Synthesis, crystal structure, and fluorescence of two dimeric europium(III) complexes with 2-(trifluoromethyl)benzoate

Two complexes [Eu2（2-TFMBA）6（2,2′-bipy）2]·2H2O （1） and Eu2（2-TFMBA）6（1,10-phen）2 （2） （2-TFMBA=2-（Trifluoromethyl） benzoate; 2,2′-bipy=2,2′-bipyridine; 1,10-phen= 1,10-phenanthroline） were synthesized by solvent method and determined by X-ray diffraction analysis. Complex 1 crystallizes in monoclinic system with space group P21/c, whereas complex 2 crystallizes in triclinic system with space group Pi. Both are binuclear molecules with an inversion center. In complex 1, two center Eu^3＋ ions are linked together by four 2-TFMBA ligands in bidentate-bridging mode. Each Eu^3＋ ion is eight-coordinated with six O atoms from five 2-TFMBA ligands and two N atoms from one 2,2′-bipy molecule. In complex 2, two center Eu^3＋ ions are linked together by four 2-TFMBA ligands in two modes, namely, bidentate-bridging and tridentate-bridging. Each Eu^3＋ ion is nine-coordinated with seven O atoms from five 2-TFMBA ligands and two N atoms from one 1,10-phen molecule. The two complexes both exhibited strong red fluorescence under ultraviolet light, and the ^5D0→^7Fj （j=0-4） transition emissions of Eu^3＋ ion were observed in their emission spectra.

A new fluorinated poly(ether amide) bearing xanthene group

A new fluorinated poly(ether amide) bearing xanthene group was prepared from 9,9-bis[4-(2-trifluoromethyl-4-aminophenox- y)phenyl]xanthene (BTFAPX) with 9,9-bis[4-(4-carboxyphenoxy)phenyl]xanthene (BCAPX) in the presence of triphenyl phos- phate and pyridine (Py). The polymer had the weight-average molecular weight (Mw) of 69,000 and number-average molecular weight (Mn) of 39,000, showed the glass transition temperature (Tg) of 267 ℃, 5% weight loss temperature (Tds) over 460 ℃ both in N2 and air, and char yield of 62% at 800 ℃ in N2. This polymer was amorphous and readily soluble in amide-type solvents such as N,N-dimethylacetamide (DMAc), and even in m-cressol, Py and tetrahydrofuran (THF) at room temperature, and exhibited tensile strength of 74 MPa, elongation at break of 6%, tensile moduli of 2.2 GPa. The polymer had low dielectric constant of 3.69 (100 Hz), low moisture absorption of 0.56%, and high transparency with an ultraviolet-visible absorption cut-off wavelength at 334 nm.

Syntheses, Crystal Structures, and Biological Activities of Two Enantiomeric 2-Trifluoromethylthieno[2,3-d]pyrimidin-4-amine Derivatives

Two enantiomeric 2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d] pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two chiral amines with 4-chloro-2-trifiuoromethyl-6,7-dihydro-5H-cyclopenta[4~5]thieno[2-3-d]pyrimidine, which started from 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, trifluoroacetic acid （TFA） and phosphoryl trichloride via one-pot procedure. Their structures were determined by single-crystal X-ray diffraction. Enantiomer （R）-3,（R）-N-（1-phenylethyl）-2-trifluoromethyl-6,7- dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system, space group P43 with a = 8.6847（6）, b = 8.6847（6）, c = 22.419（2） A, V= 1690.9（3） A3, Z = 4, Dc = 1.428 g/cm^3, p = 0.228 mm-1, F（000） = 752, the final R = 0.0463 and wR = 0.1257 for 3442 observed reflections with 1〉 20（/）. Enantiomer （S）-3,（S）-N-（1-phenylethyl）-2-trifluoromethyl-6,7-dihydro- 5H-cycloperita[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system, space group P41 with a = 8.688, b = 8.688, c = 22.421 A, V = 1692.4 A3, Z = 4, Dc = 1.426 g/cm^3, μ= 0.227 mm^-1, F（000） = 752, the final R = 0.0682 and wR = 0.1806 for 3182 observed reflections with ≥20（I）. The preliminary bioassay indicated that the R-enantiomer exhibits higher antitumor activity against MCF-7 than gefitinib.

Decorating hole transport material with −CF_(3) groups for highly efficient and stable perovskite solar cells

The hole transport material (HTM) plays an extremely important role to determine the power conversion efficiency (PCE) and the stability of perovskite solar cells (PSCs). Herein, we report an effective strategy to improve the performance of HTMs by introducing −CF_(3) groups via the rational decorative mode. Upon direct attachment or nonconjugated alkoxyl bridging of −CF_(3) groups on the terminal diphenylamines, the resulting molecular HTMs, i.e., 2,7-BCzA4CF_(3) and 2,7-BCzA4OCCF_(3), show distinct properties. Compared with 2,7-BCzA4CF_(3), the nonconjugated alkoxyl bridging −CF_(3) group-based 2,7-BCzA4OCCF_(3) exhibits better thermal stability, hydrophobicity, and a dramatically upgraded hole mobility by 135.7-fold of magnitude to 1.71 × 10^(−4) cm^(2) V^(−1) S^(−1). The PSCs with 2,7-BCzA4OCCF_(3) as HTM exhibit an PCE of up to 20.53% and excellent long-term stability, maintaining 92.57% of their performance for 30 days in air with humidity of 30% without encapsulation. This work provides beneficial guidelines for the design of new HTMs for efficient and stable PSCs.

A novel synthesis of fluvoxamine maleate

Fluvoxamine maleate is an excellent antidepressive drug. In the literatures, it was synthesized by the use of 4-（trifluoromethyl） aniline or 4-（trifluoromethyl） benzonitrile as starting materials and 5-methoxy-4＇-（trifluoromethyl-phenyl） valerophenone as a key intermediate. However, the methods in literatures have some disadvantages, such as the use of expensive materials, heavy pollution of environment, long reaction time and low yield of the product （only 30-40% overall yield）. We herein report an environmentally friendly synthetic method of fluvoxamine maleate, which used 4-（trifluoromethyl） benzoic acid and tetrahydrofuran as starting materials and FeCI3 as catalyst for the coupling of acid chloride with Grignard reagent. The fluvoxamine maleate was synthesized in 46% overall yield, through the oximation, etheration and salification of the intermediate successively.This method has some advantages, such as the use of commercially available materials, low cost, short production period （12-14 h）, high yield and light pollution.