4-(7-甲氧基-2,2-二甲基-2,3-二氢苯并呋喃-5-基)-2-芳氨基噻唑的合成、晶体结构与杀虫活性

以2-(2-甲基烯丙氧基)苯酚为原料, 经Claisen重排、呋喃环化、醚化、Friedel-Crafts乙酰化、α-溴代和噻唑环化等反应合成了22种4-(7-甲氧基-2,2-二甲基-2,3-二氢苯并呋喃-5-基)-2-芳氨基噻唑化合物. 化合物的结构经质谱、1H NMR和元素分析等确证. 采用单晶X射线衍射仪测定了化合物7j的晶体结构, 该晶体属于单斜晶系, 空间群为C2/c, 晶胞参数a=2.21140(12) nm, b=0.87602(5) nm, c=2.13911(12) nm, β=115.5380(10)°; V=3.7391(4) nm3, Z=8, Dc=1.375 g/cm3, F(000)=1616, S=1.046, μ=0.333 mm-1, 最终偏差因子R1=0.0390, wR2=0.1079. 杀虫活性实验结果表明, 化合物7a, 7b, 7h和7t在浓度为500 mg/L时对蚕豆蚜死亡率分别为95.12%, 62.60%, 57.53%和59.06%.     

4-(7-Methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-N-(pyridin-2-yl)thiazol-2-amine:Chiral Crystal from Achiral Molecule

The title compound 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-N- (pyridin-2-yl) thiazol-2-amine was synthesized by reacting 2-bromo-1-(7-methoxy-2,2-dime-thyl-2,3-dihydrobenzofuran-5-yl)ethanone with 1-(pyridine-2-yl)thiourea, and its crystal was determined by single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, chiral space group C2 with a = 18.1328(14), b = 5.5969(5), c = 19.2195(15),μ= 115.5420(10)°, V = 1759.9(2)3, Z = 4, F(000) = 744, C19H19N3O2S, Mr = 353.43, Dc = 1.334 g/cm3, S = 1.15, μ = 0.201 mm-1, the final R = 0.035 and wR = 0.111 for 2307 observed reflections (I > 2δ(I)). The Flack parameter is -0.03(10). The preliminary bioassay result indicated that the title compound exhibits strong insecticidal activity (93.75% mortality) against Mythimna separate at the concentration of 1.000 g/L.     

4-(7-甲氧基-2,2-二甲基-2,3-二氢苯并呋喃-5-基)-2-苄亚氨基噻唑的合成与生物活性

呋喃酚经醚化、傅克酰化、α-溴代、噻唑环化和亚胺化等反应合成了16种4-(7-甲氧基-2,2-二甲基-2,3-二氢苯并呋喃-5-基)-2-苄亚氨基噻唑新化合物.化合物的结构经1H NMR、质谱和元素分析等确证.杀虫活性实验结果表明,化合物2a和2i在500 mg/L对棉红蜘蛛死亡率分别为53.10%和67.71%,杀菌活性实验结果表明,化合物2a和2k在25 mg/L对油菜菌核病菌抑制率分别为57.9%和59.8%,除草活性实验结果表明,2l在2250 g.ai/ha浓度下对苘麻、刺苋、藜具有一定的除草活性.     

Synthesis, Crystal Structure and Antitumor Activity of 4-tert-Butyl-N-（2-fluorophenyl）-5- （1H-1,2,4-triazol-1-yl）-thiazol-2-amine

The title compound has been synthesized by the reaction of 1-bromo-3,3-dime- thyl-1- (1H-1,2,4-triazol-1-yl)butan-2-one with 1-(2-fluorophenyl)thiourea, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to the orthorhombic system, space group Pbca with a=15.2568(6), b=12.1533(5), c=16.7307(7) , Z=8, V=3102.2(2)3, Mr=317.39, Dc=1.359 g/cm3, S=1.05, μ=0.223 mm-1, F(000)=1328, the final R=0.034 and wR=0.097 for 2590 observed reflections (I>2σ(I)). X-ray crystal structure presents the intramolecular N-H…N hydrogen bond, which plays an important role in stabilizing the crystal structure. In addition, the preliminary biological test on the title compound shows good antitumor activity, with IC50 of 0.122 μmol/mL against the Hela cell line.     

Synthesis,Crystal Structure and Antitumor Activity of 2-(3-Methyl-5-(methylthio)-4H-1,2,4-triazol-4-yl)isoindoline-1,3-dione

The title compound 2-(3-methyl-5-(methylthio)-4H-1,2,4-triazol-4-yl)isoindoline-1,3-dione(C12H10N4O2S, Mr = 274.30) has been synthesized by a three-step procedure including the cyclization, hydrazinolysis and substitution reactions, and its crystal structure was determined by X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P21/c with a = 12.264(3), b = 14.646(3), c = 14.349(4) , β = 91.69(3)°, μ = 0.255 mm-1, Mr = 274.30, V = 2576.2(10) 3, Z = 8, Dc = 1.414 g/cm3, F(000) = 1136, R = 0.0487 and w R = 0.1329 for 4048 observed reflections with Ⅰ 2σ(Ⅰ). In addition, the preliminary bioassay suggested that the title compound 6 exhibits relatively good antitumor activity against HT-29 and MCF-7.     

Synthesis,Crystal Structure and Biological Activity of 2-((2,2-Dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)-N-(3-(furan-2-yl)-1-phenyl-1H-pyrazol-5-yl)acetamide

The title compound 2-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)-N-(3-(furan-2-yl)-1-phenyl-1H-pyrazol-5-yl) acetamide(C25H23N3O4, Mr = 429.46) has been synthesized, and its structure was characterized by 1H-NMR, 13C-NMR, H RMS, and single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, space group P21/c with a = 20.6205(18), b = 5.2930(5), c = 18.9282(17) ?, β = 94.089(2)°, V = 2060.6(3) ?3, Z = 4, Dc = 1.384 g/cm~3, μ(Mo Ka) = 0.71073 mm~(-1), F(000) = 904, R = 0.0345 and w R = 0.0930. The intramolecular hydrogen bond at N(1)–H(1)···O(2), intermolecular weak interactions at O(3)···H(4) and weak π-π interactions connected the molecules to lead to one-dimensional tapes. Bioassay results indicated that the title compound had moderate herbicidal and fungicidal activities.     

Synthesis, Crystal Structure and Antitumor Activity of （E）-4-tert-Butyl-N-（2,4-dichlorobenzylidene）-5-（1,2,4-triazol-1-yl）-thiazol-2-amine

The title compound (E)-4-tert-butyl-N-(2,4-dichlorobenzylidene)-5-(1,2,4-triazol-1-yl)-thiazol-2-amine was synthesized by the reaction of 4-tert-butyl-5-(1,2,4-triazol-1-yl)-thiazol-2-amine with 2,4-dichlorobenzaldehyde, and its crystal structure was determined by singlecrystal X-ray diffraction. The crystal belongs to the triclinic system, space group P1 with a = 7.9748(4), b = 10.1803(5), c = 11.4603(6), α = 102.882(1), β = 100.253(1), γ = 104.457(1)°, V = 850.95(7)3, Z = 2, F(000) = 392, C16H15Cl2N5S, Mr = 380.29, Dc = 1.484 g/cm3, S = 1.095, μ = 0.512 mm-1, the final R = 0.0301 and wR = 0.0965 for 3334 observed reflections (I 2σ(I)). The preliminary antitumor activity shows that for the title compound the IC50 of Hela is 0.175 μmol/mL and that of Bel7402 is 0.156 μmol/mL.     

Synthesis,Crystal Structure and Antitumor Activity of 4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)-N-(2-hydroxy-3,5-diiodinebenzyl)-thiazol-2-amine

The title compound, 4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)-N-(2-hydroxy-3,5-diiodinebenzyl)thiazol-2-amine, was synthesized via the reduction of 4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)-N-benzylidene-thiazol-2-amine with Na BH4, and its crystal structure was determined by single-crystal X-ray diffraction. The compound crystallizes in monoclinic system, space group P21/c with a = 7.91944(19), b = 10.5250(3), c = 24.4985(6) , Z = 4, V = 2041.66(9) 3, Mr = 599.22, Dc = 1.949 Mg/m3, S = 1.120, μ = 3.203 mm-1, F(000) = 1152, the final R = 0.0283 and wR = 0.0592 for 3490 observed reflections(Ⅰ 2σ(Ⅰ)). X-ray analysis displays that the crystal water takes part in three intermolecular hydrogen bonds of O(2)–H(2A)···O(1), O(2)–H(2B)···N(1) and N(5)–H(5)···O(2), and an octatomic ring is formed via intramolecular hydrogen bond of O(1)–H(1A)···N(4). Furthermore, the Ⅰ···Ⅰ contacts are involved in stabilizing the overall three-dimensional network structure. The preliminary biological test shows the title compound has good antitumor activity with the IC50 value of 26 μM against the Hela cell line.     

N-芳亚甲基-4-(4-甲氧基苯基)-5-(1H-1,2,4-三唑-1-基)-1,3-噻唑-2-胺的合成与生物活性

通过2-氨基-4-(4-甲氧基苯基)-5-(1H-1,2,4-三唑-1-基)-1,3-噻唑与取代苯甲醛发生缩合,合成了一系列新型含三唑环的噻唑席夫碱类化合物.利用1H NMR和元素分析对所有化合物进行了结构表征.初步的毒性试验表明,部分标题化合物具有一定的抗肿瘤活性.     

Synthesis,Dimeric Crystal Structure,and Fungicidal Activity of 1-(4-Methylphenyl)-2-(5-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)ethanone

Abstract

A new triazole compound, C₄₆H₄₆N₁₀O₂S₂, has been synthesized, and the crystal structure was determined by a single crystal X-ray diffraction study. The fungicidal activity of the title compound was determined, and the results showed that it displays moderate fungicidal activity.

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GRAPHICAL ABSTRACT      

Synthesis,Crystal Structure and Antitumor Activity of(E)-N-(4-Fluorobenzylidene)-3-(methylthio)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazol-4-amine

The crystal structure of the title compound(E)-N-(4-fluorobenzylidene)-3-(methylthio)-5-(3,4,5-trimethoxyphenyl)-4 H-1,2,4-triazol-4-amine(C_(19)H_(19)FN_4O_3S,Mr = 402.44) was synthesized,and its structure was characterized by 1 H-NMR,13 C-NMR,ESI-MS and single-crystal X-ray diffraction.The crystal belongs to the triclinic system,space group P1 with a = 9.228(13),b = 10.364(14),c = 10.641(14) ?,α = 85.323(3),β = 75.172(2),γ = 80.903(3)°,μ = 0.20 mm~(-1),M_r = 402.44,V = 970.64(10) ?~3,Z = 2,D_c = 1.377 g/cm~3,F(000) = 420,R = 0.0484 and wR = 0.1474 for 3181 observed reflections with I 2σ(I).In addition,the preliminary bioassay indicated that the title compound 5 exhibits better inhibitory activity against Hela than 5-fluorouracil.     

Synthesis,Crystal Structure and URAT1 Inhibitory Activity of 2-((5-Bromo-4-((4-cyclobutylnaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetic Acid

The title compound 1 was prepared from 1-bromonaphthalene and cyclobutanone in 11 steps, and its structure was determined by single-crystal X-ray diffraction for its monohydrate. The title compound 1 crystallizes as its monohydrate(C_(19)H_(18)BrN_3O_2S·H_2O, M_r = 450.35) in triclinic, space group P1 with a = 8.195(3), b = 8.703(3), c = 14.610(4) ?, α = 90.290(4), β = 93.764(9), γ = 116.435(10)°, V = 930.3(5) ?~3, Z = 2, D_c = 1.608 g/cm~3, F(000) = 460, μ = 2.347 mm~(-1), the final R = 0.0314 and wR = 0.0746 for 3368 observed reflections(I 2σ(I)). The cyclobutane ring adopts a puckered conformation. The crystal lattice is stabilized by three intermolecular hydrogen bonds involving the existing water molecule. 1 was a highly active urate transporter 1(URAT1) inhibitor as it was 14-fold more active in in vitro human URAT1 inhibitory assay versus positive control lesinurad(IC_(50) = 0.51 μM for 1 vs. 7.18 μM for lesinurad against human URAT1). The single-crystal structure for the monohydrate of 1 reported herein represents the first unambiguous structural determination of a novel flexible molecular scaffold we discovered earlier that was very promising for the design of highly active URAT1 inhibitors.     

Synthesis of 3-methyl-4-(5-R-1H-1,2,4-triazol-3-yl)-1,2,5-oxadiazoles

A number of 3-methyl-4-(5-R-1H-1,2,4-triazol-3-yl)-1,2,5-oxadiazoles were obtained in high yields by thermal dehydration of acylated 4-methyl-1,2,5-oxadiazole-3-carboxamide hydrazones.     

Synthesis,Crystal Structure and Biological Activity of 2-Chloro-5-(((5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)thiazole

The title compound 5-chloro-2-(((5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)thiazole(C17H12Cl F3N6S2) was synthesized, and its structure was confirmed by 1H NMR, 13 C NMR, HRMS and X-ray diffraction. It crystallizes in the triclinic system, space group P1 with a = 8.214(5), b = 10.188(6), c = 12.378(7) ?, α = 81.679(8), β = 87.994(8), γ = 70.351(8)°, D_c = 1.572 g/cm~3, Z = 2, V = 965.2(9) ?~3, the final R = 0.0591 and w R = 0.1113 for 3005 observed reflections with I 2σ(I). The preliminary biological test shows that the title compound possesses good herbicidal activities(80%) against rape at 200 μg/mL.     

Synthesis,Crystal Structure and Anti-breast Cancer Activity of ((3S,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl 4-Methylbenzenesulfonate

The new heterocycle compound ((3S,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (1), designed using((3R,5S)-5-(2,4-difluorophenyl)-5-iodotetrahydrofuran-3-yl)methyl isobutyrate(2) as the start material, was successfully obtained via multiple synthesis route and finally characterized by IR, ~1H NMR, and single-crystal X-ray crystallography. In addition, the in vitro anticancer activities of the newly synthesized complex 1 have been emulated against three human breast cancer cell lines BT474, MCF7 and MB.     

Synthesis,Crystal Structure and Antimicrobial Activity of Ethyl 2-（1-cyclohexyl-4-phenyl-1H-1,2,3-triazol-5-yl）-2-oxoacetate

A novel 1,4,5-trisubstituted 1,2,3-triazole(C18H21N3O3) was synthesized by a one-pot three component reaction of 1-azidocyclohexane, 1-copper(I) phenylethyne and ethoxalyl chloride at room temperature. The molecular structure was determined by single-crystal X-ray analysis. The compound crystallizes in the monoclinic system, space group P21/n with a = 12.8167(9), b = 8.0966(6), c = 16.7079(9) , β = 98.716(2)o, Z = 4 and V = 1713.8(2). In the crystal, the molecules are related by inversion and paired into dimers via C–H···O and C–O···C interactions involving(oxo) acetate groups. Furthermore, X-ray analysis results are compared with the optimized structure computed by using B3 LYP method with 6-311 G basis set. The calculated results showed that optimized geometry can well reproduce the crystal structure parameters. The bioassay results indicate that the compound has good antibacterial and antifungal activities.     

六(3,3-二甲基-1-(1H-1,2,4-三唑)-2-丁酮)锌高氯酸盐配合物的合成及晶体结构

3，3-二甲基-1－（1H－1，2，4-三唑）－2-丁酮的锌配合物（C48H78Cl2N18O14Zn）已被合成。X-射线衍射结构分析表明，晶体属单斜晶系，空间群P21／n，晶体学数据：晶体体积结构偏离因子，标题配合物分子中6个三唑环上的4位N原子与Zn原子配位，形成八面体结构，锌原子处在结晶学的对称中心上。