Synthesis and Evaluation of Antimicrobial Activity of Some New Hetaryl‐Azoles Derivatives Obtained from 2‐Aryl‐4‐methylthiazol‐5‐carbohydrazides and Isonicotinic Acid Hydrazide

A series of new 1,3,4‐oxadiazole/thiadiazole and 1,2,4‐triazole derivatives have been synthesized starting from 2‐aryl‐4‐methylthiazol‐5‐carbohydrazides and isonicotinic acid hydrazide. All the newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectrometry. The synthesized compounds were screened for their antibacterial and antifungal activity, assessed as growth inhibition diameter. Some of them showed good antibacterial activity against gram positive Staphylococcus aureus, while the antibacterial activity against Listeria monocytogenes, Escherichia coli, and Salmonella typhymurium and antifungal activity against Candida albicans was modest. None of the tested compounds showed inhibitory activity against gram positive bacteria Enterococcus faecalis and Bacillus cereus and against gram negative bacteria Pseudomonas aeruginosa.     

Synthesis of New Triazole and Oxadiazole Derivatives of Quinazolin‐4(3H)‐one and Their Antimicrobial Activity

A series of new triazole derivatives of quinazolin‐4(3H)‐one and new oxadiazole derivatives of quinazolin‐4(3H)‐one were synthesized. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR and mass spectral data. All the newly synthesized compounds were screened for antibacterial activity against Staphylococcus aureus, Bacillus subtilis (gram‐positive bacteria), Escherichia coli, Pseudomonas aeruginosa (gram‐negative bacteria), and antifungal activity was carried out against Candida albicans and Aspergillus niger.     

Design,Synthesis, and Biological Activity of Novel Triazole Sulfonamide Derivatives Containing a Benzylamine Moiety

The triazole sulfonamide played a very important role in the field of research of new agrochemical compounds as a novel heterocyclic compound with lack of reported resistance. For the research on the innovative triazole sulfonamide fungicide effective against cucumber downy mildew (CDM), the present article designed an array of 1,2,4‐triazole‐1,3‐disulfonamide derivatives. The derivatives were synthesized via coupling multiple benzylamine with triazole sulfonamide groups. ¹H‐NMR, ¹³C‐NMR, and LC–MS spectrometry were used to characterize these synthesized compounds. Most of these derivatives exhibited better fungicidal activities than that of the commercial cyanosole using bioassays. In particular, compounds 6g and 6h showed the best fungicidal activity against CDM (EC₅₀ = 6.91 and 10.62 mg/L). Comparative experiments demonstrated that the fungicidal activity of 6g and 6h was better than the commercial pesticides amisulbrom and cyanosole. According to the study, the compound 6g had a giant application potential on fungicide against CDM.     

Synthesis and Biological Activity of Novel Furan/Thiophene and Piperazine‐Containing (Bis)1,2,4‐triazole Mannich Bases

Series of novel furan/thiophene and piperazine‐containing 1,2,4‐triazole Mannich bases and bis(1,2,4‐triazole) Mannich bases have been conveniently synthesized via Mannich reaction with triazole Schiff bases, various piperazine derivatives, and formaldehyde as intermediates in good yields. Their structures were characterized by melting points, ¹H NMR, ¹³C NMR, IR and elemental analysis. The preliminary bioassay showed that most compounds exhibited significant in vitro and in vivo fungicidal activity against several test plant fungi. Among 32 new compounds, the trifluoromethyl‐containing compounds showed superior activity than the methyl‐containing ones. Several compounds, such as F8 , F9 , F10 , G5 , H7 , H8 , I3 and I4 , were comparable with some commercial fungicides against different fungi during the present study and could be further structurally optimized. Meanwhile, several compounds showed good herbicidal activity against Brassica campestris at 100 µg/mL and KARI inhibitory activity at 200 µg/mL. However, compounds exhibited poor insecticidal activity against oriental armyworm at 200 µg/mL in the preliminary studies. The research results will provide useful information for the design and discovery of new agrochemicals with novel heterocyclic structures.     

Synthesis of Polysubstituted‐1,2,4‐Triazoles

A new series of substituted 1,2,4‐triazole derivatives have been synthesized using substituted imido derivatives and isonicotinyl hydrazine (or 4‐nitrobenzoylhydrazine) as the key intermediates. These compounds include different donor or acceptor substituents on the 1,2,4‐triazole derivatives. The structures of these compounds were confirmed by FTIR, ¹H‐NMR, ¹³C‐NMR, and elemental analysis.     

Synthesis and Antibacterial Evaluation of Some Semicarbazides and 1,2,4‐Triazol‐5‐Ones Containing Thiophene Moieties

In this study, some 3‐(thiophen‐2‐ylmethyl)‐4‐substituted‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐one derivatives were synthesized by the cyclization reaction of 1‐(thiophen‐2‐ylacetyl)‐4‐substituted semicarbazide derivatives in alkaline medium or in the immediate reaction of thiophen‐2‐yl‐acetic acid hydrazide with isocyanates. The structures of all new compounds were confirmed by analytical and spectroscopic methods. Selected derivatives were evaluated in vitro against several species of aerobic bacteria. Some of them showed activity against S. pyogenes, P. aeruginosa and S. aureus.     

Synthesis and Insecticidal Activity of Tetrazole‐Linked Triazole Derivatives

A new series of 4‐(4‐substitutedbenzylideneamino)‐5‐((1‐methyl‐1H‐tetrazol‐5‐ylthio)methyl)‐4H‐1,2,4‐triazole‐3‐thiol derivatives ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k ) are prepared using 4‐amino‐5‐((1‐methyl‐1H‐tetrazol‐5‐ylthio)methyl‐4H‐1,2,4‐triazole‐3‐thiol ( 4 ), as an intermediate compound. The structures of all the newly synthesized products are established supported by their spectral ¹H NMR, ¹³C NMR, FTIR, electrospray ionization mass spectrometry (mass), and analytical data. All the compounds are screened for their insecticidal activity against Plodia interpunctella, and six compounds exhibited significant activity.     

Synthesis and Antifungal Activity of Novel 1,2,4‐Triazole Derivatives Containing 1,2,3‐Thiadiazole Moiety

Starting from carbonic acid diethyl ester, a series of 1,2,4‐triazole derivatives containing 1,2,3‐thiadiazole were synthesized. Reactions were performed by microwave irradiation or ultrasonic irradiation as well as by conventional heating. The structure of title compounds was characterized by ¹H‐NMR, MS, and elemental analyses. The fungicidal activities of these compounds were tested in vivo. Most of title compounds exhibited good antifungal activity against Pseudoperonospora cubensis. Some of title compounds displayed moderate antifungal activities against Fusarium oxysporum, Pseudoperonospora cubensis, Sphaerotheca fuligenea, Corynespora cassiicola, and Xanthomonas axonopodis.     

Green Synthesis of 1‐(1,2,4‐Triazol‐4‐yl)spiro[azetidine‐2,3′‐(3H)indole]‐2′,4′(1′H)‐diones as Potential Insecticidal Agents

One pot green synthesis of 1‐(1,2,4‐triazol‐4‐yl)spiro[azetidine‐2,3′‐(3H)‐indole]‐2′,4′(1′H)‐diones was carried out by the reaction of indole‐2,3‐diones,4‐amino‐4H‐1,2,4‐triazole and acetyl chloride/chloroacetyl chloride in ionic liquid [bmim]PF₆ with/without using a catalyst. It was also prepared by conventional method via Schiff's bases, 3‐[4H‐1,2,4‐triazol‐4‐yl]imino‐indol‐2‐one. Further, the corresponding phenoxy derivatives were obtained by the reaction of chloro group attached to azetidine ring with phenols. The synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR, and FAB mass) data. Evaluation for insecticidal activity against Periplaneta americana exhibited promising results.     

4,5-二氢-1,2,4-三唑-5-硫酮席夫碱的合成和生物活性

以4-氨基-4,5-二氢-3-苯氧甲基-1氢-1,2,4-三唑-5-硫酮与取代苯甲醛为原料反应制得了9个新的三唑硫酮席夫碱类化合物,经IR、1H NMR和元素分析确定了各化合物结构。初步室内毒力测试结果表明该类化合物其具有较好的杀菌活性。     

Synthesis and in vitro Biological Evaluation of Some Novel Triazole‐Based Heterocycles as Potential Antimicrobial Agents

A series of novel 6‐{5‐aryl‐4H‐1,2,4‐triazol‐3‐ylthio}methyl‐3‐substituted‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles and 2‐{(5‐aryl‐4H‐1,2,4‐triazol‐3‐ylthio)‐N‐4‐aryl}acetamides containing 1,2,4‐triazole moiety were synthesized and characterized by ¹H, ¹³C, DEPT, and D₂O. The synthesized compounds were evaluated for their antibacterial activity against three strains of bacteria along with antifungal activity against five fungal species. It has been found that tested compounds showed moderate activity.     

Design,Synthesis and Biological Evaluation of Isothiazole Based 1,2,4‐Trizaole Derivatives

A series of novel 3,4‐dichloroisothiazole based 1,2,4‐triazole derivatives were rationally designed and synthesized. Their structures were confirmed by ¹H NMR, ¹³C NMR, HRMS or elemental analysis; the typical crystal structure was determined by X‐ray diffraction for validation. All target compounds were evaluated for their in vitro fungicidal and in vivo anti‐TMV activities. The bioassay results indicated that compound 6b , namely 1‐(3,4‐dichloroisothiazol‐5‐yl)‐1‐(4‐fluorophenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethanol, exhibited excellent growth inhibition against B. cinerea, C. arachidicola and P. piricola with median effective concentrations (EC₅₀) of 6.98, 2.73 and 3.07 μg/mL, respectively, and good in vivo anti‐TMV activity of over 60% of inactivation and induction activity at 100 μg/mL. These data demonstrate that compound 6b is both a fungicide and an anti‐TMV lead, deserving further studies.     

Synthesis and antimicrobial and pharmacological properties of new thiosemicarbazide and 1,2,4‐triazole derivatives

Reaction of 4‐phenyl‐4H‐1,2,4‐triazole‐3‐thione with ethyl bromoacetate has led to the formation of ethyl [(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)sulfanyl]acetate 1 , the structure of which was confirmed by X‐ray analysis. In the next reaction with 80% hydrazide hydrate, appropriate hydrazide 2 was obtained, which in reaction with isothiocyanates was converted to new acyl derivatives of thiosemicarbazides 2 , 3 , 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h . The cyclization of these compounds in alkaline media has led to formation of new derivatives of 5‐{[(4‐phenyl‐4H‐1,2,4‐triazole‐3‐yl)sulfanyl]methyl}‐4H‐1,2,4‐triazole‐3(2H)‐thiones 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4j . The structure of the compounds was confirmed by elementary analysis and IR, ¹H‐NMR, ¹³C‐NMR, and MS spectra. Compounds 2 , 3 , 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h and 4a , 4b , 4c , 4d , 4e , 4f , 4g were screened for their antimicrobial activities, and the influence of the compounds 4a , 4b , and 4e , 4f , 4g on the central nervous system of mice in behavioral tests was examined. J. Heterocyclic Chem., (2011).     

Synthesis and Insecticidal Evaluation of Novel Phthalic Diamides Containing 1,2,3‐Triazoles via Click Reaction

A series of novel phthalic diamide derivatives containing 1,2,3‐triazole moiety were synthesized using one‐pot click chemistry approach and characterized by ¹H NMR and HRMS. The insecticidal activity against armyworm (Mythimna separata), Tetranychu scinnabarinus and cowpea aphid (Aphis craccivora) was evaluated. Compounds 4II‐a and 4II‐i showed 50% insecticidal activity against armyworm (Mythimna separata) at the concentration of 4 mg/L and one‐third of the compounds had moderate activity against Tetranychus cinnabarinus at 500 mg/L.     

Synthesis and Anticancer Evaluation of Some Novel 5‐Amino[1,2,4]Triazole Derivatives

Novel [1,2,4]triazole derivatives were synthesized via various synthetic pathways. Among which were different substituted [1,2,4]triazole analogues that were synthesized, in addition to various fused [1,2,4]triazolo[1,5‐a]pyrimidine derivatives, [1,2,4]triazolo[1,5‐a][1,3,5]triazines, and [1,2,4]triazolo[5,1‐c][1,2,4]triazines. Besides, benzo[h][1,2,4]triazolo[5,1‐b]quinazolines, [1,2,4]triazolo‐[5,1‐b]quinazoline, [1,2,4]triazolo[1,5‐a]quinazoline and [1,2,4]triazolo[5,1‐d][1,2,3,5]tetrazine derivatives were also synthesized. The newly synthesized compounds were evaluated for their in vitro anticancer activity against liver cancer HepG2 and breast cancer MCF7 cell lines compared with the reference drug doxorubicin. Compounds 4 , 7 , 15 , 17 , 28 , 34 , and 47 were found to exert promising anticancer activity against HepG2 cell line showing IC₅₀ values ranging from 17.69 to 25.4 μM/L, while compounds 7 , 14a , 17 , 28 , and 34 showed significant activity against MCF7 cell line with IC₅₀ values ranging from 17.69 to 27.09 μM/L.     

Synthesis and Characterization of Novel Arylaldehyde (Arylketone)‐(4‐Substituted phenyl‐5‐Substituted phenoxy‐Methyl‐4H‐1,2,4‐Triazole‐3‐yl)‐Thiol Acetyl Hydrazones

Fourteen novel arylaldehyde (arylketone)‐(4‐substituted phenyl‐5‐substituted phenoxy‐methyl‐4H‐1,2,4‐triazole‐3‐yl)‐thiol acetyl hydrazone derivatives ( 5a‐5g, 6a‐6g ) were synthesized by 4‐substituted phenyl‐5‐substituted phenoxy‐methyl‐1,2,4‐triazole‐3‐thione as starting material according to substructure link principle, followed by thioetherification, hydrazide hydrazone reaction. The structures of these compounds were confirmed by IR, ¹H NMR and elemental analysis. Crystal structure of compounds 1b and 6d were determined by the X‐ray diffraction.     

Synthesis of Some N-Alkoxycarbonyl-N″-benzoyl-benzamidrazones（p-toluamidrazones） and 1,3,5-Trisubstituted 1,2,4-Triazole Derivatives from N-Benzoylimidates and their Antimicrobial and Anticancer Screening Studies

Some new N-alkoxycarbonyl-N″-benzoyl-benzamidrazones （p-toluamidrazones） 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, ^1H NMR, ^13C NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer （MCF7）, non small cell lung cancer （NCI-H460）, and CNS cancer （SF-268） at the National Cancer Institute （NCI）, USA, which were found to exhibit low antiproliferative activity.     

Synthesis of Some New 1,2,4‐Triazole Derivatives by Mitsunobu Chemistry

The reactive 1 : 1 intermediate produced in the reaction between triphenylphosphine and diisopropyl azodicarboxylate has been trapped by isocyanates or isothiocyanates to yield 1,2,4‐triazole derivatives 2 (Scheme 1). The structures of the highly functionalized compounds 2 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, EI‐MS) and by elemental analyses. A mechanism for this type of cyclization is proposed (Scheme 2).     

Synthesis and pharmacological properties of N‐substituted‐N′‐(4,6‐dimethylpyrimidin‐2‐yl)‐thiourea derivatives and related fused heterocyclic compounds

A series of new N‐Substituted‐N′‐(4,6‐dimethylpyrimidin‐2‐yl)‐thiourea derivatives ( 3a , 3b , 3c , 3d ) and related fused heterocyclic compounds ( 4a , 4b , 4c , 4d ) were synthesized using tetrabutylammonium bromide as phase transfer catalyst (PTC). N‐[(2E)‐5,7‐dimethyl‐2H‐[1,2,4] thiadiazolo [2,3‐a] pyrimidin‐2‐ylidene] derivatives ( 4a , 4b , 4c , 4d ) were prepared by oxidative cyclization of 3a , 3b , 3c , 3d . The structures of these novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectrometry, and the elemental analysis. The crystal structures were determined from single crystal X‐ray diffraction data. The results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms and showed higher activity against fungi than bacteria. Compounds 3d and 3a exhibited the greatest antimicrobial activity. J. Heterocyclic Chem., 2011.     

Synthesis and Acaricidal Activity of Some New 1,2,4‐Triazine Derivatives

A new series of 1,2,4‐triazine derivatives were designed, synthesized, and identified on the basis of IR, ¹H‐NMR, ¹³C‐NMR, and EI‐MS spectral data. The potent acaricidal activity of 1,2,4‐triazine derivatives against eggs and adult female of Tetranychus urticae (Koch) was assessed compared with pyridaben under laboratory conditions. Structure acaricidal activity relationships of the promising 1,2,4‐triazine derivatives were analyzed for eggs and adult female; the nature and position of the substituents were important in demonstration of the activities.