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 Novel 3‐Acetyl‐2‐Aryl‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐yl)‐2,3‐Dihydro‐1,3,4‐Oxadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐oxadiazole derivatives ( 4a‐4o ) were prepared by cyclization of the intermediate N′‐((3‐aryl‐l‐phenyl‐pyrazol‐4‐yl)methylene)arylhydrazide with acetic anhydride. The structures of the new compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Furthermore, preliminary bioassay of some of the title compounds indicated that they exhibited moderate inhibition against HIV‐1 PR.     

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.     

Synthesis of 5‐(6‐Pyridazinone‐3‐yl)‐2‐Glycosylamino‐1,3,4‐Oxadiazoles

N‐Glycosyl‐2‐(1,4,5,6‐tetrahydropyridazin‐6‐one‐3‐carbonyl)‐hydrazinecarbothioamides 3a‐3g and N‐glycosyl‐2‐(1,6‐dihydropyridazin‐6‐one‐3‐carbonyl)‐hydrazinecarbothioamides 5a‐5g were prepared by the reaction of glycosyl isothiocyanates with the compounds 1,4,5,6‐tetrahydro‐3‐hydrozinecarbonyl‐6‐pyridazinone ( 1 ) and 1,6‐dihydro‐3‐hydrozinecarbonyl‐6‐pyridazinone ( 2 ). The terminal heterocyclic compounds 1,3,4‐oxadiazole derivatives were obtained from cyclization of compounds ( 3a‐3g ) and ( 5a‐5g ) by mercuric acetate. Their structures were confirmed by IR, ¹H NMR, MS and elemental analyses.     

A New Route to Synthesis of 3,6‐Diaryl‐1,2,4‐triazolo[3,4‐b]1,3,4‐oxadiazoles

Five new 3,6‐diaryl‐1,2,4‐triazolo[3,4‐b]1,3,4‐oxadiazole derivatives were synthesized by 9 steps from aromatic acids and evaluated for their activities of anticancer and antibacteria. The structures of all new compounds synthesized were elucidated by MS, IR, ¹HNMR and HRMS.     

In(OTf)3催化下水相合成2-(3,4,5-三甲氧基苯基)-5-[(5-烷硫基-1,3,4-噁二唑-2-基)硫甲基]-1,3,4-噻二唑类衍生物

以2-巯基-5-(3,4,5-三甲氧基苯基)-1,3,4-噻二唑为原料,经醚化、酰肼化、闭环、硫醚化四步反应合成了10个2-(3,4,5-三甲氧基苯基)-5-[(5-烷硫基-1,3,4-噁二唑-2-基)硫甲基]- 1,3,4-噻二唑类衍生物。通过元素分析、IR、MS、1H NMR和 13C NMR对目标化合物进行了表征。采用In(OTf)3催化下40 oC水相合成目标化合物,具有反应条件温和、合成收率高、催化剂可循环使用等特点。     

Synthesis and Fluorescent Properties of 2‐Arylamino‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐Yl)‐1,3,4‐Thiadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐thiadiazole derivatives ( 6a‐6d, 7a‐7d, 8a‐8d ) were prepared by cyclization of the intermediate 3‐aryl‐l‐phenyl‐pyrazol‐4‐ylformaldehyde 4′‐phenylthiosemicarbazones with 0.5 M ferric chloride solution. The structures of the new compounds were confirmed by IR, ¹H NMR and elemental analysis. Simultaneously, the compounds were detected by fluorescence spectrophotometer and had preferable fluorescence activity.     

Synthesis,Structure and Biological Activities of Novel 2‐(Trifluoromethyl)‐ 6‐arylimidazo[2,1‐b][1,3,4]‐thiadiazole (bis‐)Mannich Base Derivatives Containing Substitutedpiperazine Moiety

A convenient and practicable method for the synthesis of the novel 2‐(trifluoromethyl)‐6‐arylimidazo[2,1‐b][1,3,4]‐thiadiazole (bis‐)Mannich base derivatives containing various substitutedpiperazine motif has been developed based on the fused‐heterocycle intermediate. The new structures were identified through melting points, ¹H NMR, ¹³C NMR, ¹⁹F NMR, elemental analysis (or HRMS) and X‐ray single‐crystal diffraction. The pesticidal bioassays showed that some of compounds exhibited good fungicidal activities against Cercospora arachidicola, Physalospora piricola and Rhizoctonia cereali at 50 mg/L; some of them displayed favourable insecticidal activities against oriental armyworm (Mythimna separata Walker) at 200 mg/L, particularly, Vk and Vm with mortality rate of 75% and 80% respectively, could be considered as new insecticidal lead compounds for further structural optimization.     

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.     

The Synthesis of 2‐(Chromon‐2/3‐yl)‐3‐(5‐thione‐4‐hydro‐1,3,4‐thiadiazol‐2‐yl)‐4‐oxo‐thiazolidine

2‐Formylchromones and 3‐formylchromones as the first materials singly reacted with 2‐amino‐5‐mercapto‐1,3,4‐thiadiazole to give the corresponding Schiff bases, which on cyclocondensation with mercapto‐acetic acid in 1,4‐dioxane yielded target compounds named 4‐oxo‐thiazolidines. The structures of all the synthetic compounds were confirmed by elemental analysis and IR, ¹H NMR, LC‐MS (ESI) spectral data.     

Synthesis and Antibacterial Activities of 2‐(1‐Aryl‐5‐Methyl‐1,2,3‐triazol‐4‐yl)‐1,3,4‐Oxadiazole Derivatives

Eighteen novel 2‐(1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,3,4‐oxadiazole derivatives and two acylhydrazone intermediate compounds were synthesized by various pathways starting from 1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐formhydrazide ( 1 ). All products were identified by spectroscopic analysis, and 2‐(1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐5‐benzalthio‐1,3,4‐oxadiazole was further validated by X‐ray crystallography. Results from primary antibacterial activity tests indicated that most of the compounds were effective against E. coli, P. aeruginosa, B. subtilis and S. aureus.     

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 and Antifungal Screening of 2‐(2‐Aryl‐4‐methyl‐thiazol‐5‐yl)‐5‐((2‐aryl/benzylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole Derivatives

A new series of synthesis and biological screening of 2‐(2‐aryl‐4‐methyl‐thiazol‐5‐yl)‐5‐((2‐aryl/benzylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole derivatives 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i was achieved by condensation of 2‐(2‐aryl/benzylthiazol‐4‐yl)acetohydrazide 2a , 2b , 2c with 4‐methyl‐2‐arylthiazole‐5‐carbaldehyde 3a , 3b , 3c followed by oxidative cyclization of N'‐((4‐methyl‐2‐arylthiazol‐5‐yl)methylene)‐2‐(2‐aryl/benzylthiazol‐4‐yl)acetohydrazide 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i using iodobenzene diacetate as oxidizing agent. All the synthesized compounds were screened for their in vitro antifungal activity against Candida albicans, Candida tropicalis, Aspergillus niger, and Aspergillus flavus. Some of the synthesized compounds showed good antifungal activity.     

Synthesis of 1,3,4‐Oxadiazoles and 1,3‐Thiazolidinones Containing 1,4,5,6‐Tetrahydro‐6‐pyridazinone

The reaction of 1,4,5,6‐tetrahydro‐6‐pyridazinone‐3‐carboxylic acid hydrazides ( 1 ) with aromatic aldehydes afforded 1,4,5,6‐tetrahydro‐6‐pyridazinone‐3‐carbonyl aromatic aldehyde hydrazones ( 2a‐2g ). Heterocyclic derivatives linked 1,3,4‐oxadiazole obtained by cyclocondensation of 2a‐2g with acetic anhydride in absolute ethanol, and 2a‐2g cyclized with mercaptoacetic acid in DMF in the presence of anhydrous ZnCl₂ afforded the 1,3‐thiazolidinone derivatives. The structures of the new compounds were established by elemental analyses, IR, ¹H NMR and MS spectral data.     

Synthesis and antibacterial activity of novel series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline

A new series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline were synthesized from oxidative cyclization of N′‐((2‐(p‐tolyloxy)quinoline‐3‐yl)methylene)isonicotinohydrazide in DMSO/I₂ at reflux condition for 3–4 h. The structures of the new compounds were confirmed by elemental analyses as well as IR, ¹H‐NMR, and mass spectral data. All the synthesized compounds were screened for their antibacterial activities against various bacterial strains. Several of these compounds showed potential antibacterial activity. J. Heterocyclic Chem., (2011).     

Iodine‐Catalyzed Synthesis of Spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones under Mild Conditions

The I₂‐catalyzed preparation of spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones from 2‐aminobenzohydrazide and isatins in MeCN at room temperature in good‐to‐excellent yields is described. The structure of 3 was corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS data). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Synthesis,structure and in vitro cytotoxicity testing of some 1,3,4‐oxadiazoline derivatives from 2‐hydroxy‐5‐iodobenzoic acid

The syntheses of nine new 5‐iodosalicylic acid‐based 1,3,4‐oxadiazoline derivatives starting from methyl salicylate are described. These compounds are 2‐[4‐acetyl‐5‐methyl‐5‐(3‐nitrophenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6a ), 2‐[4‐acetyl‐5‐methyl‐5‐(4‐nitrophenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6b ), 2‐(4‐acetyl‐5‐methyl‐5‐phenyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl)‐4‐iodophenyl acetate, C₁₉H₁₇IN₂O₄ ( 6c ), 2‐[4‐acetyl‐5‐(4‐fluorophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate, C₁₉H₁₆FIN₂O₄ ( 6d ), 2‐[4‐acetyl‐5‐(4‐chlorophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate, C₁₉H₁₆ClIN₂O₄ ( 6e ), 2‐[4‐acetyl‐5‐(3‐bromophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6f ), 2‐[4‐acetyl‐5‐(4‐bromophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6g ), 2‐[4‐acetyl‐5‐methyl‐5‐(4‐methylphenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6h ) and 2‐[5‐(4‐acetamidophenyl)‐4‐acetyl‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6i ). The compounds were characterized by mass, ¹H NMR and ¹³C NMR spectroscopies. Single‐crystal X‐ray diffraction studies were also carried out for 6c , 6d and 6e . Compounds 6c and 6d are isomorphous, with the 1,3,4‐oxadiazoline ring having an envelope conformation, where the disubstituted C atom is the flap. The packing is determined by C—H…O, C—H…π and I…π interactions. For 6e , the 1,3,4‐oxadiazoline ring is almost planar. In the packing, Cl…π interactions are observed, while the I atom is not involved in short interactions. Compounds 6d , 6e , 6f and 6h show good inhibiting abilities on the human cancer cell lines KB and Hep‐G2, with IC₅₀ values of 0.9–4.5 µM.     

Characterization of 2‐aryl‐1,3,4‐oxadiazoles by 15N and 13C NMR spectroscopy

¹⁵N NMR chemical shifts of 2‐aryl‐1,3,4‐oxadiazoles were assigned on the basis of the ¹H–¹⁵N HMBC experiment. Chemical shifts of the nitrogen and carbon atoms in the oxadiazole ring correlate with the Hammett σ‐constants of substituents in the aryl ring (r² ≥ 0.966 for N atoms). ¹⁵N NMR data are a suitable and sensitive means for characterizing long‐range electronic substituent effects. Additionally, ¹³C NMR data for these compounds are presented. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis,in vitro Antimicrobial,and Cytotoxic Activities of New 1,3,4‐Oxadiazin‐5(6H)‐one Derivatives from Dehydroabietic Acid

A series of new 1,3,4‐oxadiazin‐5(6H)‐one derivatives ( 6a–n ) of dehydroabietic acid were designed and synthesized as potential antimicrobial and antitumor agents. Their structures were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. All the title compounds were evaluated for their antimicrobial activity against four bacterial and three fungal strains using the serial dilution method. Among them, compound 6e showed the highest antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) value of 1.9 μg/mL. In addition, the in vitro cytotoxic activities of the title compounds were also assayed against three human carcinoma cell lines (MCF‐7, SMMC‐7721, and HeLa) through the MTT colorimetric method. As a result, compounds 6b , 6g , 6k, and 6m exhibited significant inhibition against at least one cell line with IC₅₀ values below 10 μM. Compound 6m was especially found to be the most potent derivative with IC₅₀ values of 2.26 ± 0.23, 0.97 ± 0.11, and 1.89 ± 0.31 μM against MCF‐7, SMMC‐7721, and HeLa cells, respectively, comparable to positive control etoposide.     

Synthesis and Pharmacological Evaluation of a Novel Series of 2‐((2‐Aryl thiazol‐4‐yl)methyl)‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole Derivatives as Possible Antifungal Agents

In the present investigation, a novel series of 2‐[(2‐arylthiazol‐4‐yl)methyl]‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole derivatives were synthesized by cyclo‐condensation of 2‐(2‐substituted thiazol‐4‐yl)aceto hydrazide with carbon disulfide followed by S‐alkylation with alkyl halide in dry acetone. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis) methods. The title compounds were screened for in vitro antifungal activity and most of the synthesized compounds show moderate to good antifungal activity.