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.     

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,structure and investigations of tuberculosis inhibition activities of new 4‐methyl‐1‐substituted‐1H‐1,2,4‐triazole‐5(4H)‐thione

By the reaction aminomethylation, chloromethylation and acylation of 4‐methyl‐4H‐1,2,4‐triazole‐3‐thiol, 4‐methyl‐1‐substituted‐1H‐1,2,4‐triazole‐5(4H)‐thione 1‐8 were obtained. Molecular structure of the obtained compounds was confirmed by an elemental analysis, IR, ¹H NMR and ¹³C NMR spectra and additionally by X‐ray analysis for 2. Six new compounds 1,2,4‐7 were tested for antibacterial activity against Mycobacterium smegmatis, Mycobacterium phlei and avirulent strain Mycobacterium H₃₇Ra.     

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。     

Multicomponent Efficient Synthesis of New [1,2,4]Triazolo[3,4]thiadiazines

A series of novel triazolo thiadiazines were synthesized by a simple, highly efficient, one‐pot pseudo four component approach involving the condensation of 4‐amino‐5‐hydrazinyl‐4H‐1,2,4‐triazole‐3‐thiol ( 1 ), aromatic aldehydes ( 2 ), and various phenacyl bromides ( 3 ) with good yields. The structures of compounds were confirmed by analytical and spectral (IR, ¹H NMR, ¹³C NMR) data.     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

Synthesis and Antimicrobial Activity of a New Class of Benzazolyl Pyrazoles

A new class of benzazolyl pyrazoles were prepared from the simple substrates benzoxazol‐2‐thiol, benzothiazol‐2‐thiol, 1H‐benzimidazol‐2‐thiol and cinnamoyl chloride and tested for antimicrobial activity. The compounds 2‐(benzothiazol‐2‐ylthio)‐1‐(3‐(benzothiazol‐2‐ylthio)‐5‐phenyl‐1H‐pyrazol‐1‐yl)ethanone and 2‐(benzothiazol‐2‐ylamino)‐1‐(3‐(benzothiazol‐2‐ylthio)‐5‐phenyl‐1H‐pyrazol‐1‐yl)ethanone showed pronounced antibacterial activity against Klebsiella pneumoniae whereas 2‐(1H‐benzimidazol‐2‐ylthio)‐1‐(3‐(1H‐benzimidazol‐2‐ylthio)‐5‐phenyl‐1H‐pyrazol‐1‐yl)ethanone and 2‐(1H‐benzimidazol‐2‐ylamino)‐1‐(3‐(1H‐benzimidazol‐2‐ylthio)‐5‐phenyl‐1H‐pyrazol‐1‐yl) ethanone displayed excellent antifungal activity against Penicillium  chrysogenum.      

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).     

A Study of 5‐(1,2,4‐Triazol‐C‐yl)tetrazol‐1‐ols: Combining the Benefits of Different Heterocycles for the Design of Energetic Materials

The synthesis and full structural and spectroscopic characterization of three 5‐(1,2,4‐triazol‐C‐yl)tetrazol‐1‐ol compounds with selected energetic moieties including nitrimino ( 5 ), nitro ( 6 ) and azido ( 7 ) groups are reported. The influence of those energetic moieties as well as the C? C connection of a tetrazol‐1‐ol and a 1,2,4‐triazole on structural and energetic properties has been investigated. All compounds were well characterized by various means, including IR and multinuclear NMR spectroscopy, mass spectrometry, and DSC. The molecular structures of 5 – 8 were determined in the solid state by single‐crystal X‐ray diffraction. The standard heats of formation were calculated on the CBS‐4M level of theory utilizing the atomization energy method, revealing highly positive values for all compounds. The detonation parameters were calculated with the EXPLO5 program and compared to the common secondary explosive RDX. Additionally, sensitivities towards impact, friction and electrostatic discharge were determined.     

Synthesis and Characterization of Novel 1‐Methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazole Derivatives

A series of novel 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles was synthesized in three steps from 5‐(1‐methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones. 5‐(1‐Methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones were converted into 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles upon methylation followed by treatment with aq. KMnO₄. The reaction of 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles with Raney nickel resulted in desulphonylation to afford corresponding 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles. All the new synthesized compounds were characterized by spectral techniques.     

Synthesis and Antimicrobial Activity of New Pyrimidine Derivatives Incorporating 1H‐Tetrazol‐5‐ylthio Moiety

In this study, some new 4,6‐dimethoxy pyrimidine derivatives were synthesized. 2‐Amino‐4,6‐dimethoxy‐5‐thiocyanatopyrimidine ( 2 ) was synthesized by a reaction of 2‐amino‐4,6‐dimethoxypyrimidine with KSCN and was converted into 2‐amino‐5‐(1H‐tetrazol‐5‐ylthio)‐4,6‐dimethoxypyrimidine ( 4 ) by treatment with NaN₃ in the presence of NH₄Cl in DMF. Then, 1,5‐disubstitute tetrazole compounds were obtained from 4 by the alkylation reaction. In addition, some 2‐chloro‐4,6‐dimethoxy‐5‐substitute‐pyrimidines were synthesized by the diazotization method. The structures of these compounds were established on the basis of IR, ¹H NMR, APT, and HRMS spectral data and were evaluated for antibacterial activities against various bacterial strains. The results showed that some of these compounds exhibited good antibacterial activity as that of standard antibiotics Penicillin, Ampicillin, and Erythromycin.     

Synthesis of novel isoindolone‐based medium‐sized macromolecules and triazole containing heterocyclic compounds

A series of novel isoindolone‐based macromolecules of medium‐sized heterocyclic rings, such as 7,8‐dihydro‐6H‐benzo[4,5][1,6,3]dioxazonino[2,3‐a]isoindol‐14(9aH)‐one derivatives ( 5a‐l ), were synthesized and its frame work incorporating with a triazole moiety on phenol, ie, 2‐(4‐((1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)isoindoline‐1,3‐dione ( 9a‐f ) and also a triazole moiety on carboxylic acid, ie, (1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐yl)benzoate derivatives ( 13a‐e ) with various substitutions on aryl ring system have synthesized. All the synthesized compounds were characterized and confirmed with IR, ¹H NMR_, ¹³C NMR, and ESI mass spectral analysis.     

Synthesis of some novel 3,4,5-trisubstituted triazole derivatives bearing quinoline ring and evaluation of their antimicrobial activity

Abstract

Some new 3,4,5-trisubstituted 1,2,4-triazole derivatives were synthesized and studied for their antimicrobial activity. The lead compounds were obtained starting from 8-hydroxyquinoline and ethyl 2-chloroacetate. The obtained ester compound (1) first reacted with hydrazine hydrate (2) then with phenyl isothiocyanate (3). Ring closure by KOH led to 3-mercapto-1,2,4-triazole derivative (4). Lastly, it reacted with 2-chloro-N-(substituted (benzo)/thiazole)acetamide derivatives to obtain the final compounds (5a–j). The structural elucidation of the compounds was performed by ¹H NMR and ¹³C NMR spectroscopy and high resolution mass spectrometry techniques and elemental analysis. The synthesized compounds were investigated for their antimicrobial activities against seven bacteria and four fungi. As a result of the activity studies, it was observed that compounds N-(6-nitrobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5a) and N-(6-fluorobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5d) were the most active molecules. Also, the antifungal activity of the compounds was found to be higher than their antibacterial activity although lower than the standard drug’s potential. Additionally, the physicochemical properties of the compounds were calculated which were evaluated to be at a suitable range for oral administration.     

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.     

Synthesis,DNA binding,nuclease activity and cytotoxic studies of a wheel‐shaped octanuclear copper(II) complex based on 1,2,4‐triazole

The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds. Among the metal compounds synthesized and tested, copper compounds have received considerable attention because of their cytotoxic activity against solid tumors. A novel wheel‐shaped octanuclear copper(II) complex with a 1,2,4‐triazole derivative ligand formulated as [Cu₈L₄](ClO₄)₈?11H₂O ( 1 ) (L = 3,5‐bis((bis(2‐hydroxylethyl)amino)methyl)‐4 H‐1,2,4,‐triazole‐4‐amine) has been synthesized and structurally characterized. In 1 , eight Cu atoms are linked through 1,2,4‐triazole units and alkoxide bridges to form a centrosymmetric octanuclear Cu(II) metallomacrocycle. The interaction of complex 1 with calf thymus DNA has been studied using UV absorption, fluorescence and circular dichroism spectroscopies, viscosity measurements and cyclic voltammetry. The apparent binding constant (k_app) value for 1 is 1.59 × 10⁵ M^?1. Furthermore, complex 1 displays efficient oxidative cleavage of supercoiled DNA in the presence of external agents, the rate constant for the conversion of supercoiled to nicked DNA being 2.67 × 10^?5 s^?1. Interestingly, cytotoxicity studies on the MCF‐7 human breast cancer cell line show that the IC₅₀ value of 1 is less than that of cisplatin for the same cell line, revealing that it has the potential to act as an effective metal‐based anticancer drug. Copyright © 2016 John Wiley & Sons, Ltd.     

New Route for the Synthesis of Hetaryl‐1,5‐benzodiazepines: Part 2

1,2,4‐Triazin‐3‐ylthio‐, 1,2,4‐triazepin‐3‐ylthio‐, 1,2,4‐triazol‐3‐ylthio‐, and 1,2,4,3‐triazaphosphol‐5‐ylthio‐1,5‐benzodiazepines 4 – 20 were prepared via the reaction of 2‐oxo‐4‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepin‐3‐ylhydrazonothiocarbamate ( 2 ) with halocompounds, dicarbonyl compounds, enaminones, 4‐chlorobenzaldehyde, 4‐chlorobenzylidenemalononitriles, N,N‐dimethylformamide dimethylacetal, carbon disulfide, and 2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane‐2,4‐disulfide (Lawesson's reagent).     

Synthesis and Characterization of Bis(triaminoguanidinium) 5,5′‐Dinitrimino‐3,3′‐azo‐1H‐1,2,4‐triazolate – A Novel Insensitive Energetic Material

The synthesis of 5,5′‐diamino‐3,3′‐azo‐1H‐1,2,4‐triazole ( 3 ) by reaction of 5‐acetylamino‐3‐amino‐1H‐1,2,4‐triazole ( 2 ) with potassium permanganate is described. The application of the very straightforward and efficient acetyl protection of 3,5‐diamino‐1H‐1,2,4‐triazole allows selective reactions of the remaining free amino group to form the azo‐functionality. Compound 3 is used as starting material for the synthesis of 5,5′‐dinitrimino‐3,3′‐azo‐1H‐1,2,4‐triazole ( 4 ), which subsequently reacted with organic bases (ammonia, hydrazine, guanidine, aminoguanidine, triaminoguanidine) to form the corresponding nitrogen‐rich triazolate salts ( 5 – 9 ). All substances were fully characterized by IR and Raman as well as multinuclear NMR spectroscopy, mass spectrometry, and differential scanning calorimetry. Selected compounds were additionally characterized by low temperature single‐crystal X‐ray diffraction measurements. The heats of formation of 4 – 9 were calculated by the CBS‐4M method to be 647.7 ( 4 ), 401.2 ( 5 ), 700.4 ( 6 ), 398.4 ( 7 ), 676.5 ( 8 ), and 1089.2 ( 9 ) kJ · mol^–1. With these values as well as the experimentally determined densities several detonation parameters were calculated using both computer codes EXPLO5.03 and EXPLO5.04. In addition, the sensitivities of 5 – 9 were determined by the BAM drophammer and friction tester as well as a small scale electrical discharge device.     

Synthesis of Novel Spiro Thiazolotriazole Derivatives via 1,3‐Dipolar Cycloaddition of Azomethine Ylide

The 1,3‐dipolar cycloaddition of azomethine ylide generated in situ from isatin and sarcosine to 5‐arylmethylidene thiazolo[3,2‐b][1,2,4]triazol‐6(5H)‐ones afforded novel 1′‐methyl‐4′‐aryldispiro[indole‐3,2′‐pyrrolidine‐3′,5″‐[1,3]thiazolo[3,2‐b][1,2,4]triazole]‐2,6″ (1H)‐diones in moderate yields. The structures of all the products were characterized thoroughly by NMR, infrared spectroscopy (IR), mass spectroscopy (MS) elemental analysis together with X‐ray crystallographic analysis.     

Synthesis and Molecular Structure of New S‐Nucleosides of 5‐(4‐Pyridyl)‐4‐Aryl‐4H‐1,2,4‐Triazole‐3‐Thiols

The synthesis of some new S‐nucleosides of 5‐(4‐pyridyl)‐4‐aryl‐4H‐1,2,4‐triazole‐3‐thiols ( 4a‐n ) is described. Direct glycosylation of ( 4a‐n ) with tetra‐O‐acetyl‐α‐D‐glucopyranosyl bromide in the presence of potassium hydroxide followed by deacetylation using dry ammonia in methanol gave the corresponding 3‐S‐(ñ‐D‐glucopyranosyl)‐5‐(4‐pyridyl)‐4‐aryl‐4H‐1,2,4‐triazoles ( 6a‐n ) in good yields. All the compounds were fully characterized by means of ¹HNMR, ¹³C NMR spectra and elemental analyses. To assist in the interpretation of the spectroscopic data, the crystal structure of 3‐S‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl)‐5‐(4‐pyridyl)‐4‐phenyl‐4H‐1,2,4‐triazole ( 5a ) was determined by X‐ray diffraction.     

Synthesis,crystal structure,spectral characterization,and DFT studies on 4‐((1‐phenyl‐1H‐tetrazol‐5‐ylthio)methyl)benzoic acid

A new thiotetrazole compound, 4‐((1‐phenyl‐1H‐tetrazol‐5‐ylthio)methyl) benzoic acid ( 1 ), has been synthesized and characterized by elemental analysis, ¹H and ¹³C NMR, ESI‐MS, FT‐IR, UV–vis, fluorescence spectra, and single‐crystal X‐ray diffraction analysis. The structural analysis reveals that compound 1 adopts a nonplanar geometric structure and exhibits an extensive but not uniform π delocalization with all members of the tetrazolyl ring and the exocyclic sulfur atom. A density functional theory (DFT) calculation at B3LYP/6‐31G** level of theory was performed to elucidate the structure of this thiotetrazole system. And the time‐dependent DFT (TD‐DFT) calculations of absorption spectra reveal two electron‐transition bands derived from the contribution of π → π* transitions, which are in agreement with experimental results. Moreover, compound 1 exhibits a blue‐light emission (λ_em = 441 nm) in the solid state at room temperature. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:435–443, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21034