Synthesis and Antimicrobial Activity of N‐Aryl‐4‐(cyano/alkoxycarbonyl)‐5‐(pyridin‐3‐yl)‐1H/3H‐1,2,3‐triazole Derivatives

A convenient synthesis of a new series of N‐aryl‐5‐(pyridin‐3‐yl)‐1H/3H‐1,2,3‐triazole‐4‐carbonitriles and alkyl N‐aryl‐5‐(pyridin‐3‐yl)‐1H/3H‐1,2,3‐triazole‐4‐carboxylic acid esters is reported. The newly synthesized 5‐(pyridin‐3‐yl)‐1,2,3‐triazole derivatives are evaluated for their antibacterial and antifungal activity. Some of these triazole derivatives have exhibited moderate antimicrobial activity.     

The structures of 1,4‐diaryl‐5‐trifluoromethyl‐1H‐1,2,3‐triazoles related to J147, a drug for treating Alzheimer's disease

J147 [N‐(2,4‐dimethylphenyl)‐2,2,2‐trifluoro‐N′‐(3‐methoxybenzylidene)acetohydrazide] has recently been reported as a promising new drug for the treatment of Alzheimer's disease. The X‐ray structures of seven new 1,4‐diaryl‐5‐trifluoromethyl‐1H‐1,2,3‐triazoles, namely 1‐(3,4‐dimethylphenyl)‐4‐phenyl‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₇H₁₄F₃N₃, 1 ), 1‐(3,4‐dimethylphenyl)‐4‐(3‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 2 ), 1‐(3,4‐dimethylphenyl)‐4‐(4‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 3 ), 1‐(2,4‐dimethylphenyl)‐4‐(4‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 4 ), 1‐[2,4‐bis(trifluoromethyl)phenyl]‐4‐(3‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₀F₉N₃O, 5 ), 1‐(3,4‐dimethoxyphenyl)‐4‐(3,4‐dimethoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₉H₁₈F₃N₃O₄, 6 ) and 3‐[4‐(3,4‐dimethoxyphenyl)‐5‐(trifluoromethyl)‐1H‐1,2,3‐triazol‐1‐yl]phenol (C₁₇H₁₄F₃N₃O₃, 7 ), have been determined and compared to that of J147 . B3LYP/6‐311++G(d,p) calculations have been performed to determine the potential surface and molecular electrostatic potential (MEP) of J147 , and to examine the correlation between hydrazone J147 and the 1,2,3‐triazoles, both bearing a CF₃ substituent. Using MEPs, it was found that the minimum‐energy conformation of 4 , which is nearly identical to its X‐ray structure, is closely related to one of the J147 seven minima.     

‘Click Synthesis’ of 1H‐1,2,3‐Triazolyl‐Based Oxiconazole (=(1Z)‐1‐(2,4‐Dichlorophenyl)‐2‐(1H‐imidazol‐1‐yl)ethanone O‐[(2,4‐Dichlorophenyl)methyl]oxime) Analogs

The ‘click synthesis’ of some oxiconazole analogs 5a – 5v having 1H‐1,2,3‐triazolyl residues by Huisgen cycloaddition was achieved in four steps (Scheme 1). Oximation of phenacyl chloride ( 1 ) followed by azidation of 2‐chloro‐1‐phenylethanone oxime ( 2 ) provided azido ketoxime 3 . The CuI‐catalyzed Huisgen cycloaddition of 3 with terminal alkynes gave the 4‐substituted (at the triazole) 2‐(1H‐1,2,3‐triazol‐1‐yl)‐1‐phenylethanone oximes 4a – 4i . The O‐alkylation of 4a – 4i with various alkyl halides resulted in the formation of the target molecules 5a – 5v in good yields.     

1,3‐Dipolar Cycloaddition Reactions of Organic Azides with Morpholinobuta‐1,3‐dienes and with an α‐Ethynyl‐enamine

The cycloaddition of organic azides with some conjugated enamines of the 2‐amino‐1,3‐diene, 1‐amino‐1,3‐diene, and 2‐aminobut‐1‐en‐3‐yne type is investigated. The 2‐morpholinobuta‐1,3‐diene 1 undergoes regioselective [3+2] cycloaddition with several electrophilic azides RN₃ 2 ( a , R=4‐nitrophenyl; b , R=ethoxycarbonyl; c , R=tosyl; d , R=phenyl) to form 5‐alkenyl‐4,5‐dihydro‐5‐morpholino‐1H‐1,2,3‐triazoles 3 which are transformed into 1,5‐disubstituted 1H‐triazoles 4a , d or α,β‐unsaturated carboximidamide 5 (Scheme 1). The cycloaddition reaction of 4‐[(1E,3Z)‐3‐morpholino‐4‐phenylbuta‐1,3‐dienyl]morpholine ( 7 ) with azide 2a occurs at the less‐substituted enamine function and yields the 4‐(1‐morpholino‐2‐phenylethenyl)‐1H‐1,2,3‐triazole 8 (Scheme 2). The 1,3‐dipolar cycloaddition reaction of azides 2a – d with 4‐(1‐methylene‐3‐phenylprop‐2‐ynyl)morpholine ( 9 ) is accelerated at high pressure (ca. 7–10 kbar) and gives 1,5‐disubstituted dihydro‐1H‐triazoles 10a , b and 1‐phenyl‐5‐(phenylethynyl)‐1H‐1,2,3‐triazole ( 11d ) in significantly improved yields (Schemes 3 and 4). The formation of 11d is also facilitated in the presence of an equimolar quantity of tBuOH. The three‐component reaction between enamine 9 , phenyl azide, and phenol affords the 5‐(2‐phenoxy‐2‐phenylethenyl)‐1H‐1,2,3‐triazole 14d .     

2‐Triazolylpyrimido[1,2,3‐cd]purine‐8,10‐diones via 1,3‐dipolar cycloadditions to 2‐ethynylpyrimido[1,2,3‐cd]purine‐8,10‐dione

This paper presents the synthesis of a series of 5,6‐dihydro‐4H,8H‐pyrimido[1,2,3‐cd]purine‐8,10(9H)‐dione ring system derivatives with a [1,2,3]triazole ring bonded in position 2. The procedure is based on cycloaddition of substituted alkyl azides to the terminal triple bond of 5,6‐dihydro‐2‐ethynyl‐9‐methyl‐4H,8H‐pyrimido[1,2,3‐cd]purine‐8,10(9H)‐dione ( 4 ). This cycloaddition produced two regioisomers ?5,6‐dihydro‐9‐methyl‐2‐(1‐substituted‐1H‐[1,2,3]triazol‐5‐yl)‐4H,8H‐pyrimido[1,2,3‐cd]purine‐8,10(9H)‐dione ( 7 ) and 2‐(1‐substituted‐1H‐[1,2,3]triazol‐4‐yl) derivative 8 . The required 2‐ethynyl deriva tive 4 was obtained from the starting 2‐unsubstituted compound 1 by bromination to yield the 2‐bromo derivative 2 , which was converted by Sonogashira reaction to trimethylsilylethyne 3 and finally, the protective trimethylsilyl group was removed by hydrolysis.     

p‐TsOH‐mediated,Versatile, and Efficient Approach for the Synthesis of Triazolyl‐Carbazoles from Nitrovinylcarbazoles and Azide via 1, 3‐Dipolar Cycloaddition

An efficient method for the synthesis of N‐alkylated 3‐(1‐benzyl‐1H‐1,2,3‐triazole‐4‐yl)‐9H‐carbazoles ( 5 , 6 , 7 , 8 , 9 , 10 ) and 9‐ethyl‐3,6‐di(1H‐1,2,3‐triazole‐4‐yl)‐9H‐carbazole ( 13 ) has been developed from nitroolefines. The effects of catalyst and solvent on these reactions have been investigated. p‐TsOH‐THF was found to be the best system for this reaction. Various triazolyl‐carbazoles were prepared in good to excellent yields.     

A One‐Pot Tandem Ugi Multicomponent Reaction (MCR)/Click Reaction as an Efficient Protecting‐Group‐Free Route to 1H‐1,2,3‐Triazole‐Modified α‐Amino Acid Derivatives and Peptidomimetics

By a one‐pot tandem Ugi multicomponent reaction (MCR)/click reaction sequence not requiring protecting groups, 1H‐1,2,3‐triazole‐modified Ugi‐reaction products 6a – 6n (Scheme 1 and Table 2), 7a – 7b (Table 4), and 8 (Scheme 2) were synthesized successfully. i.e., terminal, side‐chain, or both side‐chain and terminal triazole‐modified Ugi‐reaction products as potential amino acid units for peptide syntheses. Different catalyst systems for the click reaction were examined to find the optimal reaction conditions (Table 1, Scheme 1). Finally, an efficient Ugi MCR+Ugi MCR/click reaction strategy was elaborated in which two Ugi‐reaction products were coupled by a click reaction, thus incorporating the triazole fragment into the center of peptidomimetics (Scheme 3). Thus, the Ugi MCR/click reaction sequence is a convenient and simple approach to different 1H‐1,2,3‐triazole‐modified amino acid derivatives and peptidomimetics.     

Green One‐Pot Solvent‐Free Synthesis of Pyrazolo[1,5‐a]pyrimidines,Azolo[3,4‐d]pyridiazines,and Thieno[2,3‐b]pyridines Containing Triazole Moiety

Synthesis of pyrazolo[1,5‐a]pyrimidines, [1,2,4]triazolo[1,5‐a]pyrimidine, 8,10‐dimethyl‐2‐(5‐methyl‐1‐phenyl‐4,5‐dihydro‐1H‐1,2,3‐triazol‐4‐yl)pyrido[2′,3′:3,4]‐pyrazolo[1,5‐a]pyrimidine, benzo[4,5]imidazo[1,2‐a]pyrimidine via heterocyclic amines, and sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole‐4‐yl)prop‐2‐en‐1‐one were carried out. Also, synthesis of isoxazoles, and pyrazoles from sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole‐4‐yl)prop‐2‐en‐1‐one and hydroxymoyl chlorides and hydrazonoyl halides, respectively, were made. Analogously, (1,2,3‐triazol‐4‐yl)thieno[2,3‐b]pyridine derivatives were obtained from sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ triazole‐4‐yl)prop‐2‐en‐1‐one and cyanothioacetamide followed by its reacting with active methylene compounds. In addition to full characterization of all synthesized compounds, they were tested to evaluate their antimicrobial activities, and some compounds showed competitive activities to those of tetracycline, the typical antibacterial drug, and clotrimazole, the typical antifungal drug.     

An efficient protocol for the one‐pot synthesis of 4‐(2‐(4‐bromophenyl)‐1,2,3‐triazol‐4‐yl)‐3,4‐dihydropyrimidin‐2(1H)‐ones/thiones catalyzed by Mg(NO3)2

A series of novel 4‐(2‐(4‐bromophenyl)‐1,2,3‐triazol‐4‐yl)‐3,4‐dihydropyrimidin‐2(1H)‐ones/thiones were prepared by condensing 2‐(4‐bromophenyl)‐4‐formyl‐1,2,3‐triazole with 1,3‐dicarbonyl compound and urea or thiourea using Mg(NO₃)₂ as an efficient and cheap catalyst. The satisfactory results were obtained with excellent yields and short reaction time. J. Heterocyclic Chem., (2010).     

Acid Catalyzed tert‐Butylation and Tritylation of 4‐Nitro‐1,2,3‐triazole: Selective Synthesis of 1‐Methyl‐5‐nitro‐1,2,3‐triazole via 1‐tert‐Butyl‐4‐nitro‐1,2,3‐triazole

4‐Nitro‐1,2,3‐triazole was found to react with tert‐butanol in concentrated sulfuric acid to yield 1‐tert‐butyl‐4‐nitro‐1,2,3‐triazole as the only reaction product, whereas tert‐butylation and tritylation of 4‐nitro‐1,2,3‐triazole in presence of catalytic amount of sulfuric acid in benzene was found to provide mixtures of isomeric 1‐ and 2‐alkyl‐4‐nitro‐1,2,3‐triazoles with predominance of N2‐alkylated products. A new methodology for preparation of 1‐alkyl‐5‐nitro‐1,2,3‐triazoles from 1‐tert‐butyl‐4‐nitro‐1,2,3‐triazole via exhaustive alkylation followed by removal of tert‐butyl group from intermediate triazolium salts was demonstrated by the example of preparation of 1‐methyl‐5‐nitro‐1,2,3‐triazole.     

2,6‐Bis(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)pyridine and its octahedral copper complex

In the tridentate ligand 2,6‐bis(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)pyridine, C₂₃H₁₉N₇, both sets of triazole N atoms are anti with respect to the pyridine N atom, while in the copper complex aqua[2,6‐bis(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)pyridine](pyridine)(tetrafluoroborato)copper(II) tetrafluoroborate, [Cu(BF₄)(C₅H₅N)(C₂₃H₁₉N₇)(H₂O)]BF₄, the triazole N atoms are in the syn–syn conformation. The coordination of the Cu^II atom is distorted octahedral. The ligand structure is stabilized through intermolecular C—H...N interactions, while the crystal structure of the Cu complex is stabilized through water‐ and BF₄‐mediated hydrogen bonds. Photoluminiscence studies of the ligand and complex show that the ligand is fluorescent due to triazole–pyridine conjugation, but that the fluorescence is quenched on complexation.     

Synthesis of Some 7H‐s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazine Derivatives

The cyclization of 1‐amino‐2‐mercapto‐5‐[5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐yl]‐1,3,4‐triazole with various α‐haloketone in absolute ethanol yields 7H‐3‐[5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐yl]‐6‐substituted‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazines and their structures are established by elemental analysis, MS, IR and ¹H NMR spectral data.     

Synthesis of some new 1‐acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazole

Some new compounds (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 5a–e were prepared by 1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐ethanone and various aromatic aldehydes. Then one pot reaction was happened by compounds 5a–e with hydrazine hydrate in acetic acid or propionic acid, respectively, to give the title compounds 1acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazoles 6a–i . All structures were established by MS, IR, CHN, ¹H‐NMR and ¹³C‐NMR spectral data. J. Heterocyclic Chem., (2012).     

Synthesis and Fungicidal Activity of (1Z, 3Z)‐4,4‐Dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one O‐[2,4‐dimethylthiazole(or 4‐methyl‐1,2,3‐thiadiazole)]‐5‐carbonyl Oximes

A series of novel (Z)‐1‐tert‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐ethanone O‐[2,4‐dimethylthiazole (or 4‐methyl‐1,2,3‐thiadiazole) ?5‐carbonyl] oximes 5a – 5c and (1Z, 3Z)‐4,4‐dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one O‐[2,4‐dimethylthiazole (or 4‐methyl‐1,2,3‐thiadiazole)‐5‐carbonyl] oximes 6a – 6e were synthesized by the condensations of (Z)‐1‐tert‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐ethanone oximes 3 or (1Z, 3Z)‐4,4‐dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one oximes 4 with 2,4‐dimethylthiazole‐5‐carbonyl chloride or 4‐methyl‐1,2,3‐thiadiazole‐5‐carbonyl chloride in the basic condition. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays showed the title compounds 5 and 6 exhibited moderate to good fungicidal activities. For example, compound 6c possessed 86.4% inhibition against Fusarium oxysporum, and compound 6b exhibited 86.4 and 100% inhibition against Fusarium oxysporum and Cercospora arachidicola Hori at the concentration of 50 mg/L, respectively.     

New 1,2,3‐triazolo[4,5‐d]1,2,4‐triazolo[3,4‐b]pyridazine derivatives II

New tricyclic 1,2,3‐triazolo‐1,2,4‐triazolo‐pyridazine derivatives, bearing a methyl substituent on the 1,2,3‐triazole ring, were prepared as potential biological agents. N‐Methylation of dimethyl 1,2,3‐triazole‐4,5‐dicarboxylate allowed synthesis of the isomeric 1‐methyl‐4,7‐dihydroxy and 2‐methyl‐4,7‐dihydroxy triazolo‐pyridazines 4a and 4b which, by a chlorination reaction, gave the corresponding 1‐methyl‐4‐chloro‐( 6a ), 1‐methyl‐7‐chloro‐ ( 6b ) and 2‐methyl‐4‐chloro‐ ( 9 ) substituted 1,2,3‐triazolo‐pyridazines. The nucle‐ophilic substitution with hydrazine hydrate and the suitable cyclization to form the 1,2,4‐triazole ring, provided the expected tricyclic isomeric derivatives 8a, 8b and 11 respectively. The p‐methoxybenzyl substituent, introduced as a leaving group to obtain either v‐triazolo‐pyridazine or v‐triazolo‐s‐triazolo‐pyri‐dazine derivatives unsubstituted on the 1,2,3‐triazole ring, appeared inadequate. Some compounds underwent binding assays toward the adenosine A₁and A_2A receptors.     

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.     

Silver Salt and Derivatives of 5‐Azido‐1H‐1, 2, 4‐triazole‐3‐­carbonitrile

This study features the preparation of three new energetic C‐azido‐1, 2, 4‐triazoles, with the anion of one being a new binary C–N compound. 5‐Azido‐1H‐1, 2, 4‐triazole‐3‐carbonitrile ( 1 ) was prepared from 5‐amino‐1H‐1, 2, 4‐triazole‐3‐carbonitrile and further derivatized to 5‐azido‐1H‐1, 2, 4‐triazole‐3‐carbohydroximoyl chloride ( 5 ) with 3‐azido‐1H‐1, 2, 4‐triazole‐5‐carboxamidoxime ( 3 ) as an intermediate. The ability of 1 and 3 for salt formation was shown with the respective silver salts 2 and 4 . All compounds were well characterized by various means, including IR and multinuclear NMR spectroscopy, mass spectrometry, and DSC. The molecular structures of 1 , 3 , and 5 in the solid state were determined by single‐crystal X‐ray diffraction. The sensitivities towards various outer stimuli (impact, friction, electrostatic discharge) were determined according to BAM standards. The silver salts were additionally tested for their potential as primary explosives.     

Synthesis and Biological Evaluation of New Ibuprofen‐1,3,4‐oxadiazole‐1,2,3‐triazole Hybrids

A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen, 1,3,4‐oxadiazole, and 1,2,3‐triazole linked through a thioether bridge was achieved by one‐pot synthesis by exploring multicomponent Cu‐catalyzed “click chemistry” approach. The target structures were characterized by NMR, IR, and LC‐Mass. The X‐ray analysis of 2‐(1‐(4‐isobutylphenyl)ethyl)‐5‐(((1‐(3‐nitrophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐1,3,4‐oxadiazole ( 8a ) confirmed the assigned structure. The in vitro antibacterial and anticancer activity of these compounds revealed that 2‐(1‐(4‐isobutylphenyl)ethyl)‐5‐(((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐1,3,4‐oxadiazole ( 8b ) demonstrated more potent antibacterial activity against Gram‐negative strains (Escherichia coli and Pseudomonas aeruginosa) and 2‐(((1‐(2,4‐dimethylphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐5‐(1‐(4 isobutylphenyl)ethyl)‐1,3,4‐oxadiazole ( 8e ) exhibited anticancer activity with IC₅₀ of 27.50 and 31.03 μg/mL against HeLa and MCF‐7 cell lines, respectively.     

Synthesis of 1‐substituted [1,2,3]triazolo[4,5‐d]pyridazines as precursors for novel tetraazapentalene derivatives

A series of 1‐substituted 4,5‐diformyl‐[1,2,3]triazole derivatives were prepared by 1,3‐dipolar cyclo‐addition of aryl azides with acetylene dicarboxaldehyde mono‐diethylacetal. The triazoles were readily converted into 1‐substituted [1,2,3]triazolo[4,5‐d]pyridazines in good yields. The 1‐(2‐nitrophenyl)‐[1,2,3]triazolo[4,5‐d]pyridazine was found to be a useful intermediate for the generation of the novel 5H‐benzo[1,2,3]triazolo[1′,2′:1,2]triazolo[4,5‐d]pyridazin‐6‐ium inner salt ring system.     

Synthesis and biological evaluation of new 4‐(4‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)phenyl)‐2‐phenylthiazole derivatives

A novel series of 4‐(4‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)phenyl)‐2‐substitutedthiazole derivatives ( 8a‐l) have been synthesized by [3 + 2] cycloaddition reaction of 4‐(4‐ethynylphenyl)‐2‐substitutedthiazole with substituted benzyl azide in aqueous DMF. Starting compounds 4‐(4‐ethynylphenyl)‐2‐substitutedthiazole ( 6a‐d ) were synthesized by reaction of 4‐(2‐substitutedthiazol‐4‐yl)benzaldehyde with Ohira‐Bestmann reagent in methanol. The structures of these novel triazole‐thiazole clubbed derivatives were confirmed by the spectral analysis. The title compounds ( 8a‐l ) were tested for antimycobacterial activity against Mycobacterium tuberculosis H37Ra active and dormant (MTB, ATCC 25177) and antimicrobial activity against standard Gram‐positive bacteria, Staphylococcus aureus (NCIM 2602) and Bacillus subtilis (NCIM 2162), and Gram‐negative bacteria, Escherichia coli (NCIM 2576) and Pseudomonas flurescence (NCIM 2059). Compounds 8a , 8b , 8c , and 8h reported good activity against B subtilis, compounds 8a , 8b , and 8c showed good activity against S aureus, and compound 8b showed good activity against dormant M tuberculosis H37Rv strain. Compounds 8b and 8c found more potent against Gram positive and dormant M tuberculosis H37Rv strains. These novel triazole‐thiazole clubbed analogues found to be a capable leads for further optimization and development.