Synthesis and Biological Activities of 7‐Arylazo‐7H‐pyrazolo[5,1‐c][1,2,4] Triazol‐6(5H)‐Ones and 7‐Arylhydrazono‐7H‐[1,2,4]triazolo[3,4‐b] [1,3,4]thiadiazines

Two series of 7‐arylazo‐7H‐3‐(2‐methyl‐1H‐indol‐3‐yl)pyrazolo[5,1‐c][1,2,4]triazol‐6(5H)‐ones 4 and 7‐arylhydrazono‐7H‐3‐(2‐methyl‐1H‐indol‐3‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines 7 were prepared via reactions of 4‐amino‐3‐mercapto‐5‐(2‐methyl‐1H‐indol‐3‐yl)‐1,2,4‐triazole 1 with ethyl arylhydrazono‐chloroacetate 2 and N‐aryl‐2‐oxoalkanehydrazonoyl halides 5 , respectively. A possible mechanism is proposed to account for the formation of the products. The biological activity of some of these products was also evaluated.     

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 of chiral fused heterocyclic compounds containing 1,2,4‐triazole ring

A series of new chiral (S)‐3‐ary1‐6‐pyrrolidin‐2‐yl‐[1,2,4]triazolo[3,4‐b]thiadiazole (II_1‐5), (S)‐1‐(3‐aryl‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐ethylamine (II_6‐8) and (S)‐1,2‐bis(3‐aryl‐[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐ethylamine (II_9‐11) were prepared by the condensation of 3‐aryl‐4‐amino‐5‐mercapto‐1,2,4‐triazoles with different L‐amino acids in the presence of phosphorus oxychloride and evaluated for their antibacterial activity.     

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 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 3‐[5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐yl]‐6‐substituted‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles

Several 3‐[5‐methyl‐1‐(4‐methylphenyl)‐1,2,3‐triazol‐4‐yl]‐6‐substituted‐1,3,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles have been synthesized and the structures of these compounds were established by elemental analysis, MS, IR and ¹H NMR spectral data.     

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.     

New CuII and CdII Metal‐organic Coordination Polymers with 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazole Ligands: Syntheses,Structures and Luminescent Properties

Three new complexes {[Cu( L¹ )₂(NO₃)₂]?H₂O}_oo ( 1 ), {[Cu₄( L² )₂(OAc)₈]‐CH₃CH₂OH}_oo ( 2 ) and [Cd₂( L³ )₃(NO₃)₄(H₂O)₂]_oo ( 3 ) ( L¹= 4‐phenyl‐7‐(pyridine‐3‐yl)‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazole, L²= 4‐(pyridine‐3‐yl)‐7‐phenyl‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazole, and L³= 4‐(pyridine‐4‐yl)‐7‐phenyl‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazole) have been synthesized and characterized by elemental analyses, IR spectra and single crystal X‐ray diffraction. The structural analyses reveal that complex 1 is a neutral 2‐D network structure with a 4⁴ topology, 2 has a 1‐D neutral coordination chain with a [Cu₂(CH₃COO)₄] dinuclear structural unit bridged by four acetate ions, and 3 is a neutral rhombohedral grid structure. All the complexes are air stable at room temperature. Furthermore, the fluorescent properties of complex 3 and corresponding ligand L³ have been investigated and discussed.     

Bis(α‐bromo ketones): Versatile Precursors for Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) and Bis(as‐triazino[3,4‐b][1,3,4]thiadiazines)

A synthesis of bis(α‐bromo ketones) 5a‐c and 6b,c was accomplished by the reaction of bis(acetophenones) 3a‐c and 4b,c with N‐bromosuccinimide in the presence of p‐toluenesulfonic acid (p‐TsOH). Treatment of 5a‐c and 6b,c with each of 4‐amino‐3‐mercapto‐1,2,4‐triazoles 9a,b and 4‐amino‐6‐phenyl‐3‐mercapto‐1,2,4‐triazin‐5(4H)‐ones 13 in refluxing ethanol afforded the novel bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) 10a‐d and 11a‐c as well as bis(as‐triazino[3,4‐b][1,3,4]thiadiazines) 14a‐c and 15 , respectively, in good yields. Compounds 11b and 11c underwent NaBH₄ reduction in methanol to give the target 1,ω‐bis{4‐(6,7‐dihydro‐3‐substituted‐5H‐1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)phenoxy}butanes 12a and 12b in 42 and 46% yields, respectively.     

Synthesis of Some Novel 3,6‐Bis(1,2,3‐triazolyl)‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazole Derivatives

The cyclization of 1‐amino‐2‐mercapto‐5‐[1‐(4‐ethoxyphenyl)‐5‐methyl‐1,2,3‐triazol‐4‐yl]‐1,3,4‐triazole which was synthesized from p‐ethoxyaniline with various triazole acid in absolute phosphorus oxychloride yields 3,6‐bis(1,2,3‐triazolyl)‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazole derivatives 9a?j , and their structures are established by MS, IR, CHN and ¹H NMR spectral data.     

Synthesis of 6‐Aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐Aryl‐thiazolo[3,2‐b][1,2,4]triazoles

The cyclization of the derivatives of 3‐aminotriazole, 2‐(5‐substituted 4H‐1,2,4‐triazol‐3‐ylamino)‐1‐arylethanones and 2‐(4H‐1,2,4‐triazol‐3‐ylthio)‐1‐arylethanones to yield 6‐aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐aryl‐thiazolo[3,2‐b][1,2,4]triazoles has been described.     

Synthesis and antimicrobial evaluation of some 1,2,4‐triazole, 1,3,4‐oxa(thia)diazole,and 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives

3‐Methyl‐2‐benzofurancarboxylic acid hydrazide ( 2 ) reacts with carbon disulfide and pota‐ ssium hydroxide to give the corresponding potassium carbodithioate salt 3 . Treatment of the latter salt with hydrochloric acid, hydrazine hydrate, and with phen‐ acyl bromide afforded the corresponding 1,3,4‐oxadia‐ zole‐5‐thione 4 , 4‐amino‐1,2,4‐triazole‐5‐thione 5 , and thiazolidine‐2‐thione 9 derivatives, respectively. The reaction of either 1,3,4‐oxadiazole‐5‐thione 4 or 4‐amino‐1,2,4‐triazole‐5‐thione 5 with phenacyl bromide resulted in the formation of 1,2,4‐triazolo[3, 4‐b]‐1,3,4‐thiadiazine derivative 8 . Treatment of compounds 3 or 4 with hydrazonoyl halides 10a–d furn‐ ished the same 1,3,4‐thiadiazol‐2‐ylidene derivatives 11a–d . The 7‐arylhydrazono‐1,2,4‐triazolo[3,4‐ b ]‐1, 3,4‐thiadiazine derivatives 12a–d were obtained either by treatment of 4‐amino‐1,2,4‐triazole‐5‐thione 5 with hydrazonoyl halides 10a–d or by coupling of the 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivative 8 with diazonium salts. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:621–627, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20162     

Synthesis and Antifungal Activities of ω‐[4‐Aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thio]‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenones

New 4‐aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thiones 3 have been synthesized by the intramolecular cyclization of 4‐aryl‐1‐(1‐phenyl‐5‐methyl‐1,2,4‐triazol‐4‐formyl)thiosemicarbazides 2 with an 8% NaOH solution, and then 3 reacted with ω‐bromo‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenone to afford ω‐[4‐aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thio]‐ω‐(1H‐1,2,4‐triazol‐1‐yl)‐acetophenones 4 . The preliminary biological test showed that the representative compounds possess some anti fungal activities.     

Synthesis of Novel 3‐(3‐(5‐Methylisoxazol‐3‐yl)‐7H‐[1,2,4]Triazolo [3,4‐b][1,3,4]Thiadiazin‐6‐yl)‐2H‐Chromen‐2‐Ones

A novel series of coumarin substituted triazolo‐thiadiazine derivatives were designed and synthesized by using 5‐methyl isoxazole‐3‐carboxylic acid ( 1 ), thiocarbohydrazide ( 2 ), and various substituted 3‐(2‐bromo acetyl) coumarins ( 4a , 4b , 4c , 4e , 4d , 4f , 4g , 4h , 4i , 4j ). Fusion of 5‐methyl isoxazole‐3‐carboxylic acid with thiocarbohydrazide resulted in the formation of the intermediate 4‐amino‐5‐(5‐methylisoxazol‐3‐yl)‐4H‐1,2,4‐triazole‐3‐thiol ( 3 ). This intermediate on further reaction with substituted 3‐(2‐bromo acetyl) coumarins under simple reaction conditions formed the title products 3‐(3‐(5‐methylisoxazol‐3‐yl)‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl‐2H‐chromen‐2‐ones ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j ) in good to excellent yields. All the synthesized compounds were well characterized by physical, analytical, and spectroscopic techniques.     

Synthesis and Reactions of 3‐Methylthiazolo[3,2‐a]Benzimidazole‐2‐Carboxylic Acid Hydrazide: Synthesis of Some New Pyrazole, 1,3‐Thiazoline, 1,2,4‐Triazole and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐Thiadiazine Derivatives Pendant to Thiazolo[3,2‐a]Benzimidazole Moiety

The reaction of 3‐methylthiazolo[3,2‐a]benzimidazole‐2‐carboxylic acid ethyl ester (1) with hydrazine hydrate gives the hydrazide 2 which reacts with CS₂/KOH to afford the potassium salt 3. Treatment of 3 with l‐aryl‐2‐bromoethanones 4a,b afforded the 1,3‐thiazoline derivatives 6a,b, respectively, while the reaction of 3 with hydrazine hydrate afforded 1,2,4‐triazole‐3‐thione derivative 9. The reaction of 9 with l‐aryl‐2‐bromoethanones 4a,b and with hydrazonyl chlorides 11a,b gave the 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives 10a,b and 12a,b, respectively. Treatment of hydrazide 2 with phenyl isothiocyanate in refluxing benzene gave the thiosemicarbazide derivative 16. The latter reaction gave 1,3,4‐oxadiazole derivative 17 when benzene was replaced by DMF. Cyclization of the thiosemicarbazide derivative 16 with NaOH resulted in the formation of the 1,2,4‐triazole‐3‐thione derivative 18.     

Synthesis and Biological Evaluation of Novel Bis[1,2,4]triazolo[3,4‐b] [1,3,4]oxadiazoles

A series of novel 6‐2‐methoxy‐5‐[4‐methoxy‐3‐(3‐aryl[1,2,4]triazolo[3,4‐b][1,3,4]oxadiazol‐6‐yl)benzyl]phenyl‐3‐aryl[1,2,4]triazolo[3,4‐b][1,3,4]oxadiazoles 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j has been synthesized and characterized via IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. Compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j were also screened for their antibacterial activity against Gram‐positive bacteria viz. Bacillus subtilis (MTCC 441), Bacillus sphaericus (MTCC 11), and Staphylococcus aureus (MTCC 96), and Gram‐negative bacteria viz. Pseudomonas aeruginosa (MTCC 741), Klobsinella aerogenes (MTCC 39), and Chromobacterium violaceum (MTCC 2656). The antibacterial screening reveal that the presence of 2,4‐difluorophenyl ( 7e ) or 4‐nitrophenyl ( 7f ) of 2‐pyrazyl ( 7i ), or 2‐furyl ( 7j ) on the triazole moiety exhibited potent inhibitory activity comparable with the standard drug streptomycin, at the tested concentrations, and emerged as potential molecules for further development.     

Conversion of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones to 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones: synthesis,spectroscopic characterization and the structures of four products and one ring‐opened derivative

An efficient synthesis of 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones, involving the diazotization of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones in weakly acidic solution, has been developed and the spectroscopic characterization and crystal structures of four examples are reported. The molecules of 1‐phenylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₉N₃O₂, (I), are linked into sheets by a combination of C—H…N and C—H…O hydrogen bonds, while the structures of 1‐(2‐methylphenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₆H₁₁N₃O₂, (II), and 1‐(3‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₈ClN₃O₂, (III), each contain just one hydrogen bond which links the molecules into simple chains, which are further linked into sheets by π‐stacking interactions in (II) but not in (III). In the structure of 1‐(4‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, (IV), isomeric with (III), a combination of C—H…O and C—H…π(arene) hydrogen bonds links the molecules into sheets. When compound (II) was exposed to a strong acid in methanol, quantitative conversion occurred to give the ring‐opened transesterification product methyl 2‐[4‐hydroxy‐1‐(2‐methylphenyl)‐1H‐1,2,3‐triazol‐5‐yl]benzoate, C₁₇H₁₅N₃O₃, (V), where the molecules are linked by paired O—H…O hydrogen bonds to form centrosymmetric dimers.     

Synthesis and Antimicrobial Evaluation of Newly Synthesized N,S‐Bisphosphonate Derivatives

An easy strategy for the synthesis of tetraethyl‐2‐(3‐mercapto‐4H‐1,2,4‐triazol‐4‐ylamino)‐2‐(aryl)ethane‐1,1‐diyldiphosphonate and tetraethyl‐(6‐(aryl)‐5,6‐dihydro[1,2,4]triazolo[3,4‐b]‐[1,3,4]thiadiazol‐6‐yl)methylenediphosphonate derivatives with reasonable 67–85% overall yields has been developed. The approach was achieved via applying Wadsworth–Horner–Emmons reagent, tetraethylmethylenebisphosphonate, to 4‐(arylideneamino)‐4H‐1,2,4‐triazole‐3‐thiols under phase‐transfer catalysis conditions. Screening results of antimicrobial potency for 12 out of 17 methylene‐1,1‐bisphosphonate products were reported. Two of the tested thiadiazolomethylenebisphosphonates displayed better spectrum of antimicrobial activity against the pathogens, compared with that of the positive controls.     

Facile one‐pot synthesis of [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines and 3,7‐dimethyl‐4H‐[1,2,4]triazino[3,4‐b][1,3,4]thiadiazin‐6‐one using heteropolyacid catalysts

[1,2,4]Triazolo[3,4‐b][1,3,4]thiadiazines 2a , 2b , 2c , 2d , 2e , 2f and 3,7‐dimethyl‐4H‐[1,2,4]triazino[3,4‐b][1,3,4]thiadiazin‐6‐one 4 were synthesized by one‐pot cyclocondensation reaction with α‐chloroacetonitrile and α‐haloketones in the presence of catalytic amounts of heteropolyacids in very high yields and rates. J. Heterocyclic Chem., (2011).     

Studies on the Reaction of α‐Chloroformylarylhydrazine Hydrochloride with Imidazole and 1,2,4‐Triazole

α‐Imidazolformylarylhydrazine 2 and α‐[1,2,4]triazolformylarylhydrazine 3 have been synthesized through the nucleophilic substitution reaction of 1 with imidazole and 1,2,4‐triazole, respectively. 2,2′‐Diaryl‐2H,2′H‐[4,4′]bi[[1,2,4]‐triazolyl]‐3,3′‐dione 4 was obtained from the cycloaddition of α‐chloroformylarylhydrazine hydrochloride 1 with 1,2,4‐triazole at 60 °C and in absence of n‐Bu₃N. The inducing factor for cycloaddition of 1 with 1,2,4‐triazole was ascertained as hydrogen ion by the formation of 4 from the reaction of 3 with hydrochloric acid. 4 was also acquired from the reaction of 3 with 1 and this could confirm the reaction route for cycloaddition of 1 with 1,2,4‐triazole. Some acylation reagents were applied to induce the cyclization reaction of 2 and 3.1 possessing chloroformyl group could induce the cyclization of 2 to give 2‐aryl‐4‐(2‐aryl‐4‐vinyl‐semicarbazide‐4‐yl)‐2,4‐dihydro‐[1,2,4]‐triazol‐3‐one 6. 7 was obtained from the cyclization of 2 induced by some acyl chlorides. Acetic acid anhydride like acetyl chloride also could react with 2 to produce 7D . 5‐Substituted‐3‐aryl‐3H‐[1,3,4]oxadiazol‐2‐one 8 was produced from the cyclization reaction of 3 induced by some acyl chlorides or acetic acid anhydride. The 1,2,4‐triazole group of 3 played a role as a leaving group in the course of cyclization reaction. This was confirmed by the same product 8 which was acquired from the reaction of 1 , possessing a better leaving group: Cl, with some acyl chlorides or acetic acid anhydride.