2-{5-[(1H-1,2,4-三唑-1-基)甲基]-4-苯基-4H-1,2,4-三唑-3-硫基}-1-芳基乙酮类化合物的合成、表征及生物活性测试

通过α-卤代芳基乙酮和5-[(1H-1,2,4-三唑-1-基)甲基]-4-苯基-2H-1,2,4-三唑-3(4H)-硫酮反应, 合成了11个新的2-{5-[(1H-1,2,4-三唑-1-基)甲基]-4-苯基-4H-1,2,4-三唑-3-硫基}-1-芳基乙酮类化合物. 其结构经元素分析, IR, ¹H NMR等确证, 并用X射线单晶衍射测定了化合物6f的晶体结构. 生物活性测试结果表明, 部分化合物具有一定的杀菌活性.     

Synthesis and biological activity research of novel ferrocenyl-containing thiazole imine derivatives

A series of novel N-substituted benzylidene-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazol-2-amine derivatives were synthesized by condensation of substituted-benzaldehydes with 2-amino-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazole and characterized by ¹H NMR, X-ray diffraction and elemental analysis. The results of bioassay showed that some title compounds exhibited some degree of plant growth regulatory and antifungal activities.     

Tautomerism of aza cycles: II. Synthesis and structure of 5-substituted 3-(2-hydroxyethylsulfanyl)-1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazoles and their salts. Preference of the 1H,4<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazolium tautomers

New complexing agents, potentially tautomeric 3-(2-hydroxyethylsulfanyl)-1H-1,2,4-triazole, its 5-methyl-and 5-phenyl-substituted analogs, and some their salts, were synthesized, and their structure was discussed on the basis of the ¹H and ¹³C NMR, IR, and mass spectra, X-ray diffraction data, and published data. In keeping with the rule formulated previously for N-unsubstituted 1,2,4-triazoles having dissimilar substituents, the synthesized compounds were found to exist as 3-(2-hydroxyethylsulfanyl)-5-R-1H-1,2,4-triazole tautomers (3-R_A-5-R_D-1H-1,2,4-triazoly). They are protonated at the nitrogen atom in position 4 of the triazole ring. The ¹H and ¹³C NMR spectra of these compounds in trifluoroacetic acid suggest the presence of two forms due to equilibrium between the neutral and protonated species. Analysis of the crystallographic data for the triazolium salts and published data showed preference of the 1H,4H-1,2,4-triazolium tautomer.     

Alkylation of C- and N-aminotriazoles with α-iodoketones

C- and N-Amino-1,2,4-triazoles react with 1-iodopropan-2-one in the absence of bases and phasetransfer catalysts (40°C, 9-12 h) to furnish 3-amino-1,4-bis(2-oxo-propyl)-4H-1,2,4-triazolium triiodide and 4-amino-1-(2-oxopropyl)-4H-1,2,4-triazolium iodide. The alkylation of 1,2,4-triazol-4-amine with 1-iodopropan-2-one and 1,3-diiodopropan-2-one in the presence of elemental iodine led to the formation of 4-amino-1-(2-oxopropyl)-4H-1,2,4-triazolium triiodide and 2-oxopropane-1,3-diylbis(4-amino-4H-1,2,4-triazolium) bis(triiodide). Triiodides are oily fluids possessing electric conductivity of 1.1 × 10^?3 Ω m^?1 opening the route to new types of electroconducting ionic liquids.     

Synthesis and antimicrobial activity of novel fused [1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indole derivatives

Synthesis of new fused systems of triazino[5,6-b]indole starting with preparation of 3-amino[1,2,4]-triazino[5,6-b]indole 1 by reaction of isatin with 2-aminoguanidinium carbonate in boiling acetic acid is presented [1]. Intermediate compound 1 reacted with aldehyde, ethyl chloroformate, triethyl orthoformate, and ninhydrine and gave new heterotetracyclic nitrogen systems, such as 3-(N ²-guanidinylimino)indole-2(1H)-one 2, 3-(N-ethoxycarbonylamino)-4H-[1,2,4]triazino[5,6-b]indole 3, 3-(N-ethoxymethyleneamino)-4H-[1,2,4]-triazino[5,6-b]indole 4, 3-(hydrazinothiocarbonylamino)-4H-[1,2,4]triazino[5,6-b]indole 5, respectively. N-(1,3-dioxoindene-2-ylidene)-4H-[1,2,4]triazino[5,6-b]indol-3-amine 6 was synthesized by reaction of compound 1 with aldehyde, ethyl chloroformate, triethyl orthoformate, and ninhydrine. New fused indole systems, pyrimido[2′,1′:3,4][1,2,4]triazino[5,6-b]indol-3(4H)-one 8, 9, 11, 12 and 1H-imidazo[2′,1′:3,4][1,2,4]triazino-[5,6-b]indol-2(3H)-one 10, were synthesized in the reaction of the intermediate 1 with bifunctional compounds. Structures of the products were elucidated from their elemental analysis and spectral data (IR, ¹H and ¹³C NMR and mass spectra). Antimicrobial activity of some synthesized compounds was tested.     

13C NMR spectra of some 1,2-disubstitutedN-vinyl-1H-1,2,4-triazoles

¹³C NMR spectra (20 and 75 MHz, in DMSO-d₆) of a series of 1,3-diaryl-3-(1H-1,2,4-triazol-1-yl)- and 1,3-diaryl-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were registered. It was shown that the chemical shifts of both the carbon atom of the alkene group and C(3) reflect regio- and stereoisomerism of these compounds. Taking this into account the isomeric structures of several 1,3-diaryl-3-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were identified and the configurations relative to the double bond of a number of 1,3-diaryl-2-(1H-1,2,4-triazol-1-yl)prop-2-en-1-ones were determined.     

Novel 2H-[1,2,4]thiadiazolo[2,3-a]pyrimidine derivatives bearing chiral S(−)-2-(4-chlorophenyl)-3-methylbutyric acid moiety: Design,synthesis and herbicidal activity

A series of S(?)-2-(4-chlorophenyl)-N-(5,7-disubstituted-2H-[1,2,4]-thiadiazolo[2,3-a]pyrimidin-2-ylidene)-3-methylbutanamide derivatives were designed and synthesized. The structures of all the newly synthesized compounds had been identified by elemental analysis, ¹H NMR, MS and optical rotation. Their herbicidal activities were evaluated against a variety of weeds. The preliminary results showed that most of the target compounds had moderate inhibitory activities and selectivities against root and stalk of monocotyledon and dicotyledon plants. More importantly, the chiral target compounds showed improved herbicidal activities to some extent over their racemic counterparts against a variety of tested weeds, which might be contributed by the introduction of chiral active unit. The present work provided a novel class of chirality-based thiadiazolopyrimidine derivatives with potent herbicidal activities for further optimization.     

Cascade reactions for constructing heterocycles containing a pyrimidino-pyrazino-pyrimidine core using 1,2,4-triazole scaffolds

The regioselective cyclocondensation of aminoethyl-1,2,4-triazoles and glyoxal provides pentacyclic heterocycles in which two 7,8-dihydro-5H-6λ²-[1,2,4]triazolo[1,5-c]pyrimidine systems are connected through CH(OH) bridges generating a central piperazine-2,5-diol ring. The structure of the new compounds was elucidated based on ¹H, ¹³C and ¹⁵N NMR spectroscopic methods. The molecular structure of the parent compound generated from aminoethyl-1,2,4-triazole was established by single crystal X-ray diffraction.     

Synthesis and biological activities of novel quinazolinone derivatives containing a 1,2,4-triazolylthioether moiety

A series of novel quinazolinone derivatives containing a 1,2,4-triazolylthioether moiety were synthesised and their antimicrobial activities were evaluated. All the target compounds were characterised by ¹H NMR, ¹³C NMR, ESI-MS, IR and elemental analyses. The single crystal structure of 3-((5-((2-fluorobenzyl)thio)-4-phenyl-4H-1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIi) was also determined. The preliminary bioassays indicated that some of the target compounds possessed good antimicrobial activities. For example, 3-((4-phenyl-5-((4-(trifluoromethyl)benzyl)thio)-4H-1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIs) exhibited the best inhibitory effect against Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri with the half-effective concentration (EC₅₀) values of 47.6 μg mL^?1 and 22.1 μg mL^?1, respectively, which were superior to the commercial bactericide, bismerthiazol. Meanwhile, 3-((5-((4-chlorobenzyl)thio)-4-phenyl-4H-1,2,4-triazol-3-yl)methyl)quinazolin-4(3H)-one (VIIh) exhibited better fungicidal activities against Pellicularia sasakii and Colletotrichum capsici at the concentration of 50 μg mL^?1, in comparison with the commercial fungicide, hymexazol.     

Synthesis and anti-microbial activity of some new fluorinated 1H-pyrazoles

Several new trifluoromethyl-1H-pyrazoles were prepared by reaction of hydrazine monohydrate with 1,3-diketones. Their structures were confirmed by elemental analysis, IR, ¹H NMR and EI-MS spectroscopy. The anti-microbial activities of the newly synthesized compounds were examined by disc diffusion method against Escherichia coli, Staphylococcus aureus, Pyricularia oryzae and Rhizoctnia solani. All the trifluoromethyl-1H-pyrazoles exhibited a certain degree of anti-bacterial and anti-fungal activities.     

Synthesis and properties of 1H-1,2,4-benzotriazepines

The synthesis of some N,N-disubstituted benzhydrazidoyl chlorides and their reaction with cyano compounds in the presence of a Lewis acid are described. Whereas N-methyl-N-phenylbenzhydrazidoyl chloride (1a) gave 1H-1,2,4-triazoles, N,N-diphenylbenzhydrazidoyl chloride (1b) afforded 1H-1,2,4-benzotriazepines (3b) and N,N-(2,2′-biphenylen)benzhydrazidoyl chloride (10) yielded the corresponding 1H-1,2,4-benzotriazepine (12) or a hydrolysis product (13). Properties of compounds 3b, specially their near-quantative acid hydrolysis to 1-phenylindazoles, are reported.     

Synthesis of spiro-fused (C5)-pyrazolino-(C6)-triazinones, a new heterocyclic system

Reaction of 4-hydrazinoquinazoline with 2,4-diketoesters gives the corresponding 3-acylmethyl-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones in a one-step procedure via cyclocondensation-Dimroth-like rearrangement. Spectroscopic studies as well as X-ray analysis reveal that the obtained triazinoquinazolines exist in their ketoimine tautomeric form. Treatment of these compounds with hydrazine hydrate affords 3′-(2-aminophenyl)-3-(het)aryl-spiro[pyrazoline-5,6′(1′H)-1,2,4-triazin]-5′(4′H)-ones or 5-(het)arylpyrazole-3-carboxylic acid hydrazides depending on the reaction conditions. The structure of the spiro-heterocycles was elucidated by means of single-crystal X-ray analysis and confirmed by spectroscopic investigations.     

Synthesis and structure of new ditopic ligands containing tetrazole and 3-nitro-1,2,4-triazole fragments

Alkylation of 3-nitro-1,2,4-triazole with haloalkyltetrazoles has afforded in high yields previously unknown 1-[2-(3-nitro-1H-1,2,4-triazol-1-yl)ethyl]-1H-tetrazole and 2-tert-butyl-5-(3-nitro-1H-1,2,4-triazol-1-ylmethyl)-2H-tetrazole. The molecular and crystal structure of these compounds has been established by X-ray diffraction analysis (XRD).     

Synthesis, structure, and photoluminescence of 5-phenyl-2-pyridyl-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazolines

The reactions of salicylaldehyde and benzoic aldehyde with 5-(2-aminophenyl)-3-pyridyl-1H-1,2,4-triazoles were studied. The reaction products are 5-phenyl-2-pyridyl-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazolines. The structures of the synthesized compounds were determined by IR spectroscopy and ¹H and ¹³C NMR spectroscopy. The luminescence properties of solutions and solid samples were studied.     

Synthesis,structure and biological activity studies of 2‐[(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1‐aryl)‐3‐ferrocenyl prop‐2‐en‐1‐one derivatives

Fifteen new ferrocene derivatives containing 1H‐1,2,4‐triazole moiety were synthesized in various yields by the condensation of ferrocenecarboxaldehyde with 1‐aryl‐3‐(1H‐1,2,4‐triazo‐1‐yl)‐propen‐1‐ones in toluene. Their structures have been confirmed by ¹H NMR, IR, MS and elemental analysis. In addition, the crystal structure of 4l was determined. The antifungal and plant growth regulatory activities of the title compounds are discussed. Copyright © 2005 John Wiley & Sons, Ltd.     

A novel synthesis of N(1)-(substituted)-pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones

A new synthesis of N₁-(substituted)-pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones, which are analogues of the natural product toxoflavin, is reported. Condensation of preformed alkyl or aryl hydrazones with 6-chloro-3-methyl-5-nitrouracil efficiently provides pyrimidotriazinediones in a three-step process that broadens the scope of R₁ substituents.     

Regioselective alkylation of 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole

Alkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole using different alkylating agents leads regioselectively to 1-N-alkylated products. The hydrolysis-decarboxylation of 1,6-dimethyl-7-ethoxycarbonyl-pyrazolo[5,1-c][1,2,4]triazole yields a compound identical with that obtained by the direct methylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole. The 1-N-alkylation is confirmed by NMR spectroscopy and mass spectrometry.     

Synthesis,characterization and biological activity of Hg(II), Fe(III) complexes with 1,3,4-oxadiazole, 1,2,4-triazole derivatives from L-methionine

Four novel heterocyclic1,3,4-oxadiazole, 1,2,4-triazole derivatives, namely: 5-[1-amino-3-(methylsulfanyl)propyl]-1,3,4-oxadiazole-2(3H)-thione (4), 4-amino-5-[1-amino-3-(methylsulfanyl)propyl]-4H-1,2,4-triazole-3-thiol (5), 1-amino-3-[1-amino-3-(methylsulfanyl)propyl]-1H-1,2,4-triazole-5-thiol (7), and 5-[1-amino-3-(methylsulfanyl)propyl]-1H-1,2,4-triazole-3-thiol (9) have been synthesized from l-methionine and characterized by different spectroscopic techniques (FT-IR, UV–Vis, ¹H NMR, ¹³C NMR and MS). Complex formation with Hg⁺⁺ and Fe⁺⁺⁺ ions were formed from the four heterocyclic 4, 5, 7 and 9. The antimicrobial activities for synthetic intermediates and final four products were assisted using paper disk diffusion method against Gram-negative bacteria: Escherichia coli, Pseudomonas aeroginosae and Gram-positive bacteria: Staphylococus aureus 25923, Staphylococus aureus 43300 and showed variant activity against some of the microorganisms tested.     

A novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan

In this study, a novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles (8) is presented starting from (1H-1,2,4-triazol-1-yl)methanol (5) and indolines (6) under 98% H₂SO₄ at room temperature for 4–24 h, followed by deacetylation and dehydrogenation. Based on this finding, a novel route to synthesize Rizatriptan starting from tryptamine was designed and accomplished with 48.5% overall yield in 6 steps. Compared with operational art, the new route afforded higher yield and more pure products requiring no chromatographic purification, which may further be applied in industrialization.     

Synthesis and pharmacological evaluation of 3-diphenylmethyl-6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles: A condensed bridgehead nitrogen heterocyclic system

A series of 3-diphenylmethyl-6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives (4a–j and 5a–d) were synthesized by condensation of 4-amino-5-diphenylmethyl-4H-1,2,4-triazole-3-thiol with various substituted aromatic acids and aryl/alkyl-isothiocyanates. The structures of synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectroscopic studies. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic, lipid peroxidation and hepatotoxic effects. Compounds 6-(4-chlorophenyl)-3-diphenylmethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (4a) and 6-(2,4-dichlorophenyl)-3-diphenylmethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole(4c) emerged as the most active compounds of the series and were moderately more potent than the standard drug ibuprofen.