Polymorphism of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐ and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐ones

This study of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐2H‐chromen‐2‐one, C₁₇H₁₀N₂O₃, 1 , and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐one, C₁₆H₉N₃O₃, 2 , was performed on the assumption of the potential anticancer activity of the compounds. Three polymorphic structures for 1 and two polymorphic structures for 2 have been studied thoroughly. The strongest intermolecular interaction is stacking of the `head‐to‐head' type in all the studied crystals. The polymorphic structures of 1 differ with respect to the intermolecular interactions between stacked columns. Two of the polymorphs have a columnar or double columnar type of crystal organization, while the third polymorphic structure can be classified as columnar‐layered. The difference between the two structures of 2 is less pronounced. Both crystals can be considered as having very similar arrangements of neighbouring columns. The formation of polymorphic modifications is caused by a subtle balance of very weak intermolecular interactions and packing differences can be identified only using an analysis based on a study of the pairwise interaction energies.     

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).     

A one‐pot efficient four‐component reaction for the synthesis of 2‐(arylamino)‐2‐(5‐aryl‐1,3,4‐oxadiazol‐2‐yl)propyl benzoate (or acetate) derivatives

Reactions of (N‐isocyanimino) triphenylphosphorane with 2‐oxopropylbenzoate (or acetate) in the presence of aromatic carboxylic acids and primary amines proceed smoothly at room temperature and in neutral conditions to afford sterically congested 1,3,4‐oxadiazole derivatives in high yields. The reaction proceeds smoothly and cleanly under mild conditions, and no side reactions were observed. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:692–698, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20735     

A Facile Synthesis of Substituted 2‐(5‐(Benzylthio)‐1,3,4‐oxadiazol‐2‐yl)pyrazine Using Microwave Irradiation and Conventional Method with Antioxidant and Anticancer Activities

A series of novel substituted 2‐(5‐(benzylthio)‐1,3,4‐oxadiazol‐2‐yl)pyrazine derivatives ( 6a – n ) were synthesized under microwave irradiation and conventional conditions with less reaction time with good to excellent yields. All the synthesized compounds were screened for antioxidant and anticancer activities. Out of the 14 prepared derivatives, compounds 6f and 6m were most potent and active with antioxidant and anticancer activities, respectively. Also, the developed technique was simple, easy, and less time consuming.     

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 biological evaluation of several 3‐(coumarin‐4‐yl)tetrahydroisoxazole and 3‐(coumarin‐4‐yl)dihydropyrazole derivatives

A series of novel 3‐(coumarin‐4‐yl)tetrahydroisoxazoles 5a,b, 7, 9 and 3‐(coumarin‐4‐yl)dihydropyra‐zoles 13a‐d, 14,15a,b were synthesized from coumarin‐4‐carboxaldehyde 1 via the intermediate N‐methyl nitrone 3 and N‐phenyl or N‐methyl hydrazones 11a,b . These coumarin derivatives were isolated, characterized and evaluated in vitro for their ability to inhibit trypsin, β‐glucuronidase, soybean lipoxygenase and to interact with the stable radical 1,1‐diphenyl‐2‐picrylhydrazyl. The compounds were tested in vivo as anti‐inflammatory agents in the rat carrageenin paw edema assay. Compound 15a seems to be a lead molecule to be modified in order to improve the lipoxygenase inhibition. The results are discussed in terms of structural characteristics.     

The Studies of Structure of 2N‐(3‐phenyl‐allyl‐)(5‐phenyl‐[1,3,4] Thiadiazol‐2‐yl) Amine in Solution

2N‐(3‐phenyl‐allyl‐)(5‐phenyl‐[1,3,4] thiadiazol‐2‐yl) amine was studied by means of the ¹H, ¹³C, ¹⁵N NMR spectroscopy and DFT calculations. On the basis of the one‐dimensional ¹H, ¹³C, ¹⁵N‐NMR and two‐dimensional ¹H‐¹³C HMQC, ¹H‐¹³C HMBC, ¹H‐¹⁵N HMQC, ¹H¹H NOESY, ¹H¹H COSY correlation spectra the amine‐type and the imine‐type tautomers have been determined in the solution. Variety of structural forms including: biradical, ionic–biradical, and ionic structures of the amine‐type a and of the imine‐type b , c tautomers exist in the solution. According to the DFT computations the differences in the total energy between a and b , a and c , and b and c tautomers are equal to 1.5 kJ/mol, 1.2 kJ/mol, and 0.3 kJ/mol, respectively.     

Syntheses of 4‐(5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones and 4‐(4‐arylamino‐5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones from Sydnone Derivatives and Their Fragments

4‐(5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones 11 and 4‐(4‐arylamino‐5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones 13 have been obtained from a‐chloroformylarylhydrazine hydrochloride 2 . Moreover, the intermediates, including 3, 4 , 9 and 10 , in this study are synthetically informative and valuable. It is also noteworthy that three reactants, 1, 2 and sydnonecarbaldehydes, were prepared from sydnone derivatives and their fragments. The oxidative cyclizations of sydnonecarbaldehyde semicarbazones 9 and carbazones 10 with two different oxidizing agents (Cu(ClO₄)₂ and Fe(ClO₄)₃) have been extensively examined. The reaction time and the yields of cyclizations were affected by the substituents of semicarbazones 9 and carbazones 10.     

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 of 5‐Hydroxy‐2‐(naphth‐2‐yl)chromone derivatives

The Diels‐Alder reaction of 5‐hydroxy‐2‐styrylchromones with ortho‐benzoquinodimethane, generated “in situ” by thermal extrusion of sulfur dioxide from 1,3‐dihydrobenzo[c]thiophene 2,2‐dioxide, leads to 2‐(3‐aryl‐1,2,3,4‐tetrahydronaphth‐2‐yl)‐5‐hydroxychromones. These cycloadducts were dehydrogenated with DDQ, using classical thermal reflux conditions and microwave irradiation, affording the corresponding 2‐(3‐arylnaphth‐2‐yl)‐5‐hydroxychromones in high yields (48‐96%).     

Antibacterial and Antifungal Activities of 2‐(substituted ether)‐5‐(1‐phenyl‐5‐(trifluoromethyl)‐1H‐pyrazol‐4‐yl)‐1,3,4‐oxadiazole Derivatives

By replacing the amide bond into 1,3,4‐oxadiazole moiety, a series of 1‐phenyl‐5‐(trifluoromethyl)‐1H‐pyrazole derivatives bearing 1,3,4‐oxadiazole were synthesized and evaluated their antibacterial and antifungal activity. The bioassay results revealed that compounds 7a and 7b showed the strongest antibacterial activity toward pathogen Xanthomonas oryzae pv. oryzae with the EC50 values of 15.0 and 6.4 µg/mL, respectively; compound 6a exhibited comprehensive antifungal activity toward six kinds of fungi; compound 6f could selectively inhibit the growth of Sclertinia sclerotiorum and Rhizoctonia solani with the inhibition rates of 82.5 and 80.3% at the concentrate of 100 µg/mL, respectively; compound 7b exerted good antifungal activity toward Fusarium oxysporum, Cytospora mandshurica, and Rhizoctonia solani with the inhibition rates of 70.8, 69.5, and 71.5%, respectively. The results suggested that this kind of compounds could be further studied as promising antimicrobial agents.     

Synthesis and Bioactivities of Novel N‐(4‐(2‐Aryloxythiazol‐5‐yl)but‐3‐yn‐2‐yl)benzamides

A series of novel N‐(4‐(2‐aryloxythiazol‐5‐yl)but‐3‐yn‐2‐yl)benzamide derivatives were designed and synthesized. Their structures were identified by ¹H NMR and elemental analyses. Preliminary bioassays indicated that some title compounds provided >80% control of Sclerotinia sclerotiorum at 50 µg/mL and >70% herbicidal activities against B. campestris at 100 µg/mL. Their structure‐activities relationships were also discussed.     

ZnII and CuII complexes generated from 5‐(pyridin‐4‐yl)‐3‐[2‐(pyridin‐4‐yl)ethyl]‐1,3,4‐oxadiazole‐2(3H)‐thione

A new 1,3,4‐oxadiazole‐containing bispyridyl ligand, namely 5‐(pyridin‐4‐yl)‐3‐[2‐(pyridin‐4‐yl)ethyl]‐1,3,4‐oxadiazole‐2(3H)‐thione (L), has been used to create the novel complexes tetranitratobis{μ‐5‐(pyridin‐4‐yl)‐3‐[2‐(pyridin‐4‐yl)ethyl]‐1,3,4‐oxadiazole‐2(3H)‐thione}zinc(II), [Zn₂(NO₃)₄(C₁₄H₁₂N₄OS)₂], (I), and catena‐poly[[[dinitratocopper(II)]‐bis{μ‐5‐(pyridin‐4‐yl)‐3‐[2‐(pyridin‐4‐yl)ethyl]‐1,3,4‐oxadiazole‐2(3H)‐thione}] nitrate acetonitrile sesquisolvate dichloromethane sesquisolvate], {[Cu(NO₃)(C₁₄H₁₂N₄OS)₂]NO₃·1.5CH₃CN·1.5CH₂Cl₂}_n, (II). Compound (I) presents a distorted rectangular centrosymmetric Zn₂L₂ ring (dimensions 9.56 × 7.06 Å), where each Zn^II centre lies in a {ZnN₂O₄} coordination environment. These binuclear zinc metallocycles are linked into a two‐dimensional network through nonclassical C—H...O hydrogen bonds. The resulting sheets lie parallel to the ac plane. Compound (II), which crystallizes as a nonmerohedral twin, is a coordination polymer with double chains of Cu^II centres linked by bridging L ligands, propagating parallel to the crystallographic a axis. The Cu^II centres adopt a distorted square‐pyramidal CuN₄O coordination environment with apical O atoms. The chains in (II) are interlinked via two kinds of π–π stacking interactions along [01]. In addition, the structure of (II) contains channels parallel to the crystallographic a direction. The guest components in these channels consist of dichloromethane and acetonitrile solvent molecules and uncoordinated nitrate anions.     

Synthesis of 3‐phenyl‐5‐(trifluoromethyl)isoxazole and 5‐phenyl‐3‐(trifluoromethyl)isoxazole

Reaction of 4,4,4‐trifluoro‐1‐phenyl‐1,3‐butanedione with hydroxylamine led to the formation of 5‐hydroxy‐3‐phenyl‐5‐(trifluoromethyl)‐4,5‐dihydroisoxazole which was dehydrated to 3‐phenyl‐5‐(trifluoro‐methyl)isoxazole. This isomer can also be synthesized by reaction of 4‐chloro‐4‐phenyl‐1,1,1‐trifluoro‐3‐buten‐2‐one with sodium azide. The regioisomer, 5‐phenyl‐3‐(trifluoromethyl)isoxazole was synthesized by reaction of 1,1,1‐trifluoro‐4‐phenylbut‐3‐yn‐2‐one with hydroxylamine and by the reaction of 3‐chloro‐1‐phenyl‐4,4,4‐trifluorobut‐2‐en‐1‐one with sodium azide. Both isomers were characterized by mass and NMR spectroscopy.     

Synthesis and herbicidal activity of 2‐(3‐(trifluoromethyl)‐5‐(alkoxy)‐1H‐pyrazol‐1‐yl)‐4‐aryloxypyrimidine derivatives

A series of 2‐(3‐(trifluoromethyl)‐5‐(alkoxy)‐1H‐pyrazol‐1‐yl)‐4‐aryloxypyrimidine derivatives were designed and synthesized. The structures of all the title compounds were confirmed by ¹H NMR and elementary analysis. These compounds were screened for herbicidal activity against rape and barnyard grass. Compound B13 exhibited moderate herbicidal activity.     

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 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.     

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.