Synthesis and Antimicrobial Activity of Some Condensed [4‐(2,4,6‐Trimethylphenyl)‐1(2H)‐oxo‐phthalazin‐2‐yl]acetic Acid Hydrazide

Some new 1,2,4‐triazolo‐, 1,3,4‐oxadiazolo‐, 1,3,4‐thiadiazol‐, and pyrazolo‐2,4,6‐trimethylphenyl‐1(2H)‐oxo‐phthalazine derivatives were synthesized and identified by IR, ¹H NMR, ¹³C NMR, MS and elemental analysis. The new compounds were synthesized with the objective of studying their antimicrobial activity.     

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).     

Synthesis and Antimicrobial Activity of Some Novel [4‐(1,2,3‐thiadiazol‐4‐yl)phenoxy]methylene anchored 1,3,4‐triazoles and 1,3,4‐thiadiazoles

A series of novel [4‐(1,2,3‐thiadiazol‐4‐yl)phenoxy]methylene anchored 1,3,4‐triazoles ( 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h ) and 1,3,4‐thiadiazoles ( 9a , 9b , 9c , 9d , 9e , 9f , 9g , 9h , 9i ) were synthesized from thiosemicarbazide ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j ). The structures of these newly synthesized compounds were confirmed on the basis of IR, ¹H‐NMR, mass spectral techniques, and elemental analysis. The in vitro antimicrobial screenings of the synthesized compounds were carried out against four bacterial pathogens, namely Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and three fungal pathogens Candida albicans, Aspergillus niger and Aspergillus clavatus, using broth microdilution minimum inhibitory concentration method. The compounds 7d , 7j , 8a , 9a , 9b , and 9i exhibited promising antibacterial activity against the tested strains, whereas some compounds were found to be active against one of the tested bacterial strains.     

Synthesis,Antimicrobial, and Antioxidant Screening of Aryl Acetic Acid Incorporated 1,2,4‐Triazolo‐1,3,4‐Thiadiazole Derivatives

Some novel [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole derivatives were synthesized from aryl acetic acids. All the synthesized derivatives were selected for the screening of antibacterial potential against Gram‐positive bacteria [Staphylococcus aureus (MTCC 3160) and Micrococcus luteus (MTCC 1538)] and Gram‐negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)] and antifungal potential against Aspergillus niger (MTCC 8652) and Candida albicans (MTCC 227), and free radical scavenging activity through 2,2‐diphenyl‐2‐picrylhydrazyl hydrate method. The compounds TH‐4 , TH‐13 , and TH‐19 were found to be more potent antimicrobial agents compared to standard drugs. The compounds TH‐3 , TH‐9 , and TH‐18 also showed significant antimicrobial activity. The compound TH‐13 showed antioxidant activity with IC₅₀ value better than the standard compound. The structures of all the synthesized compounds were confirmed by Fourier transform infrared, ¹H‐NMR, liquid chromatography–mass spectrometry, and CHN analyzer.     

Synthesis and Characterization of New Thebaine Derivatives as Potential Opioid Agonists and Antagonists: 2‐[N‐(1H‐Tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazoles

In this study, we report the synthesis a series of novel 2‐[N‐(1H‐tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazole derivatives ( 7a – e ) which have potential opioid antagonist and agonist. The substitution reaction of 6,14‐endo‐ethenotetrahydrothebaine‐7α‐carbohydrazide with corresponding benzoyl chlorides gave diacylhydrazine compounds 4a – e in good yields. The treatment of compounds 4a – e with POCl₃ caused the conversion of side‐chain of compounds 5a – e into 1,3,4‐oxadiazole ring at C(7) position; thus, compounds 5a – e were obtained. Subsequently, cyanamides ( 6a – e ) were prepared from compounds 5a – e and then compounds 7a – e were synthesized by the azidation of 6a – e with NaN₃. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C APT, 2D‐NMR (COSY, NOESY, HMQC, HMBC) and high‐resolution mass spectral data.     

Novel Approach for Rapid and Efficient Synthesis of 2‐(3‐(4‐Aryl)‐1‐isonicotinoyl‐4,5‐dihydro‐1H‐pyrazol‐4‐yl)‐3‐phenylthiazolidin‐4‐one Derivatives and Screened Their Antimicrobial Activity

A series of compounds, viz. 2‐(3‐(4‐aryl)‐1‐isonicotinoyl‐4,5‐dihydro‐1H‐pyrazol‐4‐yl)‐3‐phenylthiazolidin‐4‐one 4 ( a – n ), have been synthesized by reaction of 3 ( a – n ) with thioglycolic acid in the presence of zinc chloride. Compounds 3 ( a – n ) have been synthesized by amination of formylated pyrazoles 2 ( A – B ), which were synthesized by formylation of 1 ( A – B ) by Vilsmeier–Haack reagent (POCl₃/DMF). Compounds 1 ( A – B ) were synthesized by condensation of hydrazide and substituted acetophenones under conventional method and microwave irradiation method. These compounds were identified on the basis of melting point range, Rf values, infrared, ¹H NMR, and mass spectral analysis. These compounds were evaluated for their in vitro antimicrobial activity, and their minimum inhibitory concentration was determined. Among them, compound 4b and compound 4l possess appreciable antimicrobial and antifungal activities. Antibacterial activity results showed that compounds containing electron‐withdrawing groups were more active than compounds containing electron‐releasing groups.     

Synthesis and biological activities of a novel series of 3,6‐disubstituted‐1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazoles containing gem‐dimethylbenzyl moiety

A novel series of 3,6‐disubstituted‐1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazoles (6a–r) containing gem‐dimethyl benzyl moiety were prepared by the condensation of 4‐amino‐3‐aryl/aralkyl substituted‐5‐mercapto‐1,2,4‐triazoles ( 5a , 5b , 5c ) with various fluoro substituted aromatic acids in the presence of POCl₃. IR, ¹H NMR, ¹³C NMR, 2D NMR (COSY), and mass spectral data confirmed the structures of all the synthesized compounds. All the compounds were also screened for their antibacterial, antifungal and analgesic activities. Compounds 6b , 6d , 6f , 6g , 6h , 6i , 6m , 6n , 6o , 6p , and 6r exhibited promising antibacterial and compounds 6a , 6d , 6f , 6g , 6h , 6k , 6m , 6o , 6p , and 6q showed significant analgesic activities. J. Heterocyclic Chem., (2011)     

Synthesis and tuberculostatic activity of novel N′‐methyl‐4‐(pyrrolidin‐1‐yl)picolinohydrazide and N′‐methylpyrimidine‐2‐carbohydrazide derivatives

The synthesis of N′‐methyl‐4‐(pyrrolidin‐1‐yl)picolinohydrazide and N′‐methyl‐pyrimidine‐2‐carbohydrazide derivatives ( 5a and 5b ) was carried out. These compounds were used as starting materials to obtain methyl N′‐methylhydrazinecarbodithioates 6a and 6b , which, on reaction with either triethylamine or hydrazine, gave corresponding 1,3,4‐oxadiazioles 7a and 7b or 1,2,4‐triazoles 9a and 9b with the free NH₂ group at the N‐4 position, respectively. Compounds 8a – e , particularly containing cyclic amines at N‐4 of the 1,2,4‐triazole ring, were also obtained. Synthesized compounds were tested in vitro for their activity against Mycobacterium tuberculosis. The structure–activity relationship analysis for obtained compounds was done. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:223–230, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21008     

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 of Novel 1‐(5‐(Benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene)‐thiourea/urea Derivatives and Evaluation of Their Antimicrobial Activities

A new series of 1‐(5‐(benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene)‐thiourea/urea derivatives ( 1a – j ) were designed and synthesized. For the first time, (i) a new process was developed for N‐methylation of 1,3,4‐thiadiazole moiety using dimethyl carbonate an environmentally benign reagent in presence of N,N,N′,N′‐tetramethylethylenediamine and (ii) the sulfide was selectively oxidized to sulfoxide in higher yield by using chlorine (g) in aqueous acetic acid media under mild reaction condition. The synthesized compounds ( 1a – j ) were investigated for their antimicrobial activities. The tested compounds ( 1a – j ) were exhibited moderate to excellent antibacterial activities against both Gram‐positive and Gram‐negative bacterial strains. The same compounds exhibited good antifungal activities against selected fungal strains. Particularly, the compounds 1b , 1d , 1h , and 1i were proved to be promising leads exhibiting both antibacterial and antifungal activities compared with standard drugs, ciprofloxacin, and fluconazole. The presence of 1,3,4‐thiadiazole moiety has a significant role in the display of antimicrobial activity. In addition, the presence of both sulfinyl and thiourea or urea functionalities has enhanced the activity as per obtained antimicrobial activity data.     

Novel 7‐Nitro‐1‐(Piperidin‐4‐yl)‐4,5‐Dihydro‐[1,2,4] Triazolo[4,3‐a]Quinoline‐Sulphonamide Derivatives as Antimicrobial Agents: Design,Synthesis, and Bio‐Activity

In attempt to search for more potent antimicrobial agents, a series of 7‐nitro‐1‐(piperidin‐4‐yl)‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinoline‐derived sulphonamides were synthesized. Their structures were established by elemental analyses, IR, and NMR (¹H and ¹³C) spectral data. The antibacterial activity of the obtained compounds was investigated against different Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Bacillus subtilis and Staphylococcus aureus) bacteria and antifungal activity against two fungal strains (Aspergillus niger and Aspergillus clavatus) using disk diffusion method at various concentrations (20, 40, 60, and 80 μg/mL). The study reveals that most of the title compounds showed significant antibacterial and fungal activity when compared with their respective standards streptomycin and griseofulvin.     

Synthesis and Antimicrobial Activities of Novel Series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one Derivatives

In the present investigation, a novel series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one derivatives were synthesized by condensation of 2‐substituted‐4‐methylthiazole‐5‐carbaldehyde with 4‐(2‐substituted thiazol‐4‐yl)benzenamine followed by cyclo‐condensation with thioglycolic acid in toluene. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, and Mass) methods. The title compounds were screened for quantitative antibacterial activity (minimal inhibitory concentration). All compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h and 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h show moderate to good antimicrobial activity, whereas compounds ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h ) also show moderate antifungal activity.     

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,Characterization, and Herbicidal Activities of New 1,3,4‐Oxadiazoles, 1,3,4‐Thiadiazoles,and 1,2,4‐Triazoles Derivatives Bearing (R)‐5‐Chloro‐3‐fluoro‐2‐phenoxypyridine

Synthesis of some novel 1,2,4‐triazoles, 1,3,4‐oxadiazoles and 1,3,4‐thiadiazoles bearing a (R) 5‐(1‐(4‐(5‐chloro‐3‐fluoropyridin‐2‐yloxy)phenoxy)ethyl) unit, as a moiety of commercial herbicide, using their thiosemicarbazides in an alkaline, iodine and acidic media is reported, respectively. The structure of the synthesized compounds was characterized by IR, ¹H, ¹³C NMR spectroscopic data, and elemental analyses. The herbicidal activities of synthesized compounds were evaluated against Echinochloa cruss‐galli, Avena fatua, and Sorgum halepense weeds. Compounds 7 and 12a showed potential herbicidal activity against gramineous weeds. Our results may provide some guidance for synthesis development of some novel oxa or thiadiazole and triazole‐based herbicidal lead structures.     

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.     

Design,Synthesis, and Herbicidal Activities of 3‐Aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles

In order to find novel bleaching herbicide lead compounds, a series of novel 3‐aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles were designed and synthesized by the multi‐step reactions. N‐(Arylformamido)phenylthioureas undergo ring closure in the presence of sodium hydroxide to generate 3‐aryl‐4‐substituted‐4H‐[1,2,4]triazol‐5‐thiols 1 , which reacted with methyl sulfate in the presence of K₂CO₃ to give 3‐aryl‐5‐methylsulfanyl‐4‐substituted‐4H‐[1,2,4]triazoles 2 . The target compounds 4 were synthesized by the oxidation of 2 in the presence of H₂O₂ and Na₂WO₄, followed by the substitution with 3‐(trifluoromethyl)phenol in moderate to good yields. Their structures were confirmed by IR, ¹H NMR, EI–MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate to good selective herbicidal activity against Brassica campestris L at the concentration of 100 µg/mL. Compounds 4c and 4i possessed 75.0% and 82.6% inhibition against Brassica campestris L at the concentration of 100 µg/mL. However, the target compounds 4 showed weak herbicidal activity against Echinochloa crus‐galli at the concentration of 100 and 10 µg/mL.     

Synthesis and Antimicrobial Activity of New 2,5‐Disubstituted 1,3,4‐Oxadiazoles and 1,2,4‐Triazoles and Their Sugar Derivatives

A series of new 2,5‐disubstituted‐1,3,4‐oxadiazole and 1,2,4‐triazole derivatives were synthesized by heterocyclization of acid hydrazide 1 and thiosemicarbazide derivative 2 . Furthermore, the acyclic C‐nucleoside analogs were prepared by cyclization of their corresponding sugar hydrazones by reaction with acetic anhydride. The antimicrobial activity of the prepared compounds was evaluated and some of the synthesized compounds revealed good activities against fungi.     

Synthesis and Antimicrobial Activity of Novel 2‐Substituted Phenoxy‐N‐(4‐substituted Phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐yl)acetamide Derivatives

A series of 2‐substituted phenoxy‐N‐(4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazole‐2‐yl)acetamide derivatives 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n , 8o , 8p , 8q , 8r , 8s , 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amine 5 . Their structures were confirmed by ¹H NMR, ¹³C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae , Phytophthora infestans , and Paralepetopsis sasakii ) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo ) and Xanthomonas axonopodis pv. citri (Xac )] showing promising results. In particular, 8b , 8f , 8g , and 8h exhibited excellent antibacterial activity against Xoo , with 50% effective concentration (EC₅₀) values of 35.2, 80.1, 62.5, and 82.1 µg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 µg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.     

Synthesis,Dissociation Constants,and Antimicrobial Activity of Novel 2,3‐Disubstituted‐1,3‐thiazolidin‐4‐one Derivatives

In this article, a new series of 2,3‐disubstituted‐1,3‐thiazolidin‐4‐one derivatives have been designed, synthesized, and evaluated as antimicrobial agents. New compounds were prepared by the cyclization reaction of N‐substituted carboxylic acid hydrazide derivatives with mercaptoacetic acid. The structures of the obtained compounds were confirmed by means of IR, ¹H NMR, and ¹³C NMR spectra. The dissociation constants were determined using spectrophotometric method. All synthesized compounds were tested for their in vitro antibacterial and antifungal activities using the broth microdilution method.     

Heterocycles Derived from 5‐(2‐Aminothiazol‐4‐yl)‐8‐hydroxyquinoline: Synthesis and Antimicrobial Activity

5‐(2‐Aminothiazol‐4‐yl)‐8‐hydroxyquinoline 2 has been synthesized by treating thiourea with 5‐chloroacetyl‐8‐hydroxyquinoline 1 . The amine 2 was treated with aromatic aldehydes to furnish schiff bases 6a‐c which on treatment with phenyl isothiocyanate gave the corresponding thiazolo‐s‐triazines 7a‐c . Reaction of 2 with phenyl isothiocyanate gave the corresponding aminocarbothiamide derivative 8 which on reaction with malonic acid in acetyl chloride afforded thiobarbituric acid derivative 9 . Coupling of 9 with diazonium salt gave the phenyl hydrazono derivative 10 . However, reaction of 2 with carbon disulphide and methyl iodide afforded dithiocarbamidate 12 which on treatment with ethylenediamine, o‐aminophenol and/or phenylenediamine gave the aminoazolo derivatives 13–15 , respectively. Other substituted fused thiazolopyrimidines 16–20 have been also prepared by the reaction of 2 with some selected dicarbonyl reagents. The characterisation of synthesized compounds has been done on the basis of elemental analysis, IR, ¹H‐NMR and mass spectral data. All the newly synthesized compounds have been screened for their antimicrobial activities.