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 Antiviral Bioactivity of Novel 2‐Substituted Methlthio‐5‐(4‐Amino‐2‐Methylpyrimidin‐5‐yl)‐1,3,4‐Thiadiazole Derivatives

A series of novel 2‐substituted methlthio‐5‐(4‐amino‐2‐methylpyrimidin‐5‐yl‐)‐1,3,4‐thiadiazole derivatives were synthesized, characterized and evaluated for antiviral activities against tobacco mosaic virus (TMV). The preliminary biological results indicated that most compounds exhibit excellent antiviral activity against TMV in vivo. Among these compounds, compounds 9c , 9i , and 9p displayed the similar curative effect against TMV (EC₅₀ = 287.05–322.47 µg/mL) to that of the commercial agent Ningnanmycin (EC₅₀ = 301.83 µg/mL). In particular, compound 9d demonstrated the best curative effect against TMV (EC₅₀ = 266.21 µg/mL), which was better than that of commercial Ningnanmycin.     

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.     

2‐Amino‐5‐(2‐pyridyl)‐thiadiazole as Bidentate Ligand

The amino substituted bidentate chelating ligand 2‐amino‐5‐(2‐pyridyl)‐1,3,4‐thiadiazole (H₂ L ) was used to prepare 3:1‐type coordination compounds of iron(II), cobalt(II) and nickel(II). In the iron(II) perchlorate complex [Fe^II(H₂ L )₃](ClO₄)₂·0.6MeOH·0.9H₂O a 1:1 mixture of mer and fac isomers is present whereas [Fe^II(H₂ L )₃](BF₄)₂·MeOH·H₂O, [Co^II(H₂ L )₃](ClO₄)₂·2H₂O and [Ni^II(H₂ L )₃](ClO₄)₂·MeOH·H₂O feature merely mer derivatives. Moessbauer spectroscopy and variable temperature magnetic measurements revealed the [Fe^II(H₂ L )₃]²⁺ complex core to exist in the low‐spin state, whereas the [Co^II(H₂ L )₃]²⁺ complex core resides in its high‐spin state, even at very low temperatures.     

Synthesis of Optically Active 2‐Amino‐1,3,4‐oxadiazoles and their Hybrid Peptides

Synthesis of 2‐amino‐1,3,4‐oxadiazole derivatives of N^α‐Cbz(benzyloxycarbonyl)/Boc‐protected amino/peptide acids under sonication is described. The conditions involved in the present protocol are simple, mild, and racemization free. The utility of 2‐amino group in the substituted oxadiazoles for the incorporation of peptide and ureido bonds to obtain hybrid peptidomimetics is also delineated. The 2‐amino‐1,3,4‐oxadiazole 3b was obtained as a single crystal, and its molecular structure has been confirmed through X‐ray crystallographic study.     

Phosphosulfonic acid‐catalyzed green synthesis and bioassay of α‐aryl‐α′‐1,3,4‐thiadiazolyl aminophosphonates

A series of new α‐aminophosphonates containing 1,3,4‐thiadiazole moiety (4a–l) were synthesized via a simple, efficient, and one‐pot three‐component Kabachnik–Fields reaction of 2‐amino‐5‐ethyl‐1,3,4‐thiadiazole with various aryl/heteroaryl aldehydes and diethylphosphite under solvent‐free microwave irradiation conditions using phosphosulfonic acid, as a reusable and heterogeneous solid acid catalyst. All the title compounds were screened for radical scavenging activity by DPPH and H₂O₂ methods, and antimicrobial activity against bacteria (Gram‐positive and Gram‐negative) and fungi using the disc diffusion technique. They exhibited potent in vitro antioxidant and moderate antimicrobial activity.     

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,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.     

Synthesis of Novel 2‐Amino‐(2‐thioxo‐3‐alkyl‐4‐methyl‐3H‐thiazol‐5‐yl)‐[1,3,4]thiadiazole Derivatives and Their Growth Stimulant Activity

On the base of synthesized 2‐amino and 2‐ethylamino‐(2‐thioxo‐3‐alkyl‐4‐methyl‐3H‐thiazol‐5‐yl)‐[1,3,4]thiadiazoles, their alkyl, acetyl, and alkylacetylamino derivatives are obtained. The alkylation of 2‐ethylamino derivatives can occur at both exo and endo nitrogen atoms of amidine group, and the acetylation takes place exclusively at the exocyclic nitrogen atom. At acetylation of 2‐amino‐[1,3,4]thiadiazoles, only exo substitution is observed. At the further alkylation of these products, a mixture of exo‐ and endo‐substituted forms is obtained. At preliminary screening, the synthesized compounds have shown expressed growth stimulant properties. The activity of the most active derivatives was in the range of 65–100%, compared with that of heteroauxin.     

Structural characterization of the aquaporin inhibitor 2‐nicotinamido‐1,3,4‐thiadiazole

Nicotinamides are a class of compounds with a wide variety of applications, from use as antimicrobial agents to inhibitors of biological processes. These compounds are also cofactors, which are necessary components of metabolic processes. Structural modification gives rise to the activities observed. Similarly, 1,3,4‐thiadiazoles have been shown to possess antioxidant, antimicrobial, or anti‐inflammatory biological activity. To take advantage of each of the inherent characteristics of the two aforementioned functional groups, 2‐nicotinamido‐1,3,4‐thiadiazole, C₈H₆N₄OS, was synthesized. Since defining chemical connectivity is paramount in understanding biological activity, in this report, the structural characterization of 2‐nicotinamido‐1,3,4‐thiadiazole has been carried out using X‐ray crystallographic methods. The NMR‐derived assignments were made possible by utilizing one‐ (1D) and two‐dimensional (2D) NMR techniques. In addition, UV–Visible and IR spectroscopies, and elemental analysis were used to fully characterize the product synthesized by the one‐step reaction between nicotinoyl chloride hydrochloride and 2‐amino‐1,3,4‐thiadiazole. Computational parameters related to blood–brain barrier permeability are also presented.     

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     

2‐Amino‐7‐chloro‐2′‐deoxy­tubercidin

In 4‐chloro‐7‐(2‐de­oxy‐β‐d ‐erythro‐pento­furanos­yl)‐7H‐pyr­rolo­[2,3‐d]­pyrimidine‐2,4‐diamine, C₁₁H₁₄ClN₅O₃, the conformation of the N‐glycosylic bond is between anti and high‐anti [χ = −102.5 (6)°]. The 2′‐deoxy­ribofuranosyl unit adopts the C3′‐endo‐C4′‐exo (³T₄) sugar pucker (N‐type) with P = 19.6° and τ_m = 32.9° [terminology: Saenger (1989). Landolt‐Börnstein New Series, Vol. 1, Nucleic Acids, Subvol. a, edited by O. Madelung, pp. 1–21. Berlin: Springer‐Verlag]. The orientation of the exocyclic C4′—C5′ bond is +ap (trans) with a torsion angle γ = 171.5 (4)°. The compound forms a three‐dimensional network that is stabilized by four inter­molecular hydrogen bonds (N—H⋯O and O—H⋯N) and one intra­molecular hydrogen bond (N—H⋯Cl).     

Cyclization–oxidation of Benzylidenehydrazinecarbothioamides by FeCl3.6H2O or ZnCl2.6H2O Catalysts and Synthesis of New 1,3,4‐Thiadiazolo‐[3,2‐ α]Pyrimidines

We report new method for preparation of 2‐amino‐5‐aryl‐1,3,4‐thiadiazoles by reaction of arylaldehyde with thiosemicarbazide and in the next step via cyclization of 2‐aryl hydrazinecarbothioamide in the presence of ZnCl₂.6H₂O or FeCl₃.6H₂O. Also, in this research, new substituted 1,3,4‐thiadiazolo‐[3,2‐α]pyrimidines were synthesized by the reaction of 2‐amino‐5‐aryl‐1,3,4‐thiadiazoles derivatives with DMAD or DEAD in the presence of K₂CO₃ under reflux conditions. The FT‐IR, ¹H‐NMR, ¹³C‐NMR, elemental analysis and single‐ crystal X‐ray analysis confirm the structures of the products.     

Facile synthesis of 2‐alkylthio‐3‐amino‐4 H‐imidazol‐4‐ones and 2H‐imidazo[2,1‐b]‐1,3,4‐thiadiazin‐6(7H)‐ones via N‐vinylic iminophosphorane

2‐Alkylthio‐3‐amino‐4H‐imidazol‐4‐ ones 5 were synthesized by S‐alkylation of 2‐thioxo‐3‐amino‐4‐imidazolidinones 4 , which were obtained via cyclization of isothiocyanates 2 with hydrazine hydrate. 5l–n reacted with Ph₃P, C₂Cl₆, and NEt₃ to give 2H‐imidazo[2,1‐b]‐1,3,4‐thiadiazin‐ 6(7H)‐ones 7a–c in good yields. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:76–80, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20069     

catena‐Poly[[bis[5‐(4‐pyridyl‐κN)‐2‐(2‐pyridylmethylsulfanyl)‐1,3,4‐oxadiazole]cadmium(II)]‐di‐μ‐thiocyanato‐κ2N:S;κ2S:N]

The title compound, [Cd(NCS)₂(C₁₃H₁₀N₄OS)₂]_n, contains SCN⁻ anions acting as end‐to‐end bridging ligands which utilize both S and N atoms to link cadmium(II) centers into one‐dimensional double chains. The multidentate 5‐(4‐pyridyl)‐2‐(2‐pyridylmethylsulfanyl)‐1,3,4‐oxadiazole ligands behave as monodentate terminal ligands, binding metal centers only through the N atoms of the 4‐pyridyl groups. Two types of eight‐membered rings are formed by two SCN⁻ anions bridging Cd^II centers, viz. planar and chair conformation, which are alternately disposed along the same chain. Finally, chains define a two‐dimensional array through two different interchain π–π stacking interactions.     

2,5‐Bis[4‐methyl‐3‐(pyridin‐3‐yl)phenyl]‐1,3,4‐oxadiazole and its one‐dimensional polymeric complex with ZnCl2

2,5‐Bis[4‐methyl‐3‐(pyridin‐3‐yl)phenyl]‐1,3,4‐oxadiazole (L), C₂₆H₂₀N₄O, forms one‐dimensional chains via two types of intermolecular π–π interactions. In catena‐poly[[dichloridozinc(II)]‐μ‐2,5‐bis[4‐methyl‐3‐(pyridin‐3‐yl)phenyl]‐1,3,4‐oxadiazole], [ZnCl₂(C₂₆H₂₀N₄O)]_n, synthesized by the combination of L with ZnCl₂, the Zn^II centres are coordinated by two Cl atoms and two N atoms from two L ligands. [ZnCl₂L]_n forms one‐dimensional P (plus) and M (minus) helical chains, where the L ligand has different directions of twist. The helical chains stack together via interchain π–π and C—H...π interactions.     

Synthesis of 2‐Amino‐1,3,4‐oxadiazoles through Elemental Sulfur Promoted Cyclization of Hydrazides with Isocyanides

A novel sulfur‐promoted cyclization of hydrazides and isonitriles to produce 1,3,4‐oxadiazole has been developed. The method is operationally simple and compatible with a wide scope of substrates and various 2‐amino‐ 1,3,4‐oxadiazoles are efficiently obtained in good yields.     

Synthesis and Reactivity of 2‐Pyrrolidino‐, 2‐N‐Methylpiperazino‐, 2‐Piperidino‐, and 2‐Morpholino‐1,3,4‐thiadiazines

A variety of 2‐pyrrolidino‐, 2‐N‐methylpiperazino‐, 2‐piperidino‐, and 2‐morpholino‐1,3,4‐thiadiazines were prepared by cyclocondensation of phenacyl halides with thiosemicarbazides. Heating of the products resulted in desulfurization and formation of pyrazoles. The rate of this process strongly depends on the substitution pattern of the 1,3,4‐thiadiazines.     

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).     

New Method for the Synthesis and Reactivity of (5‐R‐1,3,4‐Oxadiazol‐2‐yl)furoxans

A new, simple and general one‐pot method for the preparation of (5‐R‐1,3,4‐oxadiazol‐2‐yl)furoxans has been developed on the basis of the interaction between accessible 3‐methylfuroxan‐4‐carboxylic acid hydrazide and aliphatic, aromatic and heterocyclic carboxylic acids or their chlorides in the presence of POCl₃. The synthesis and study of (5‐R‐1,3,4‐oxadiazol‐2‐yl)furoxans reactivity resulted in new polyheterocyclic ensembles incorporating furoxan, 1,3,4‐oxadiazole, pyrrole, triazole, furan, thiophene, pyrimidine, and other heterocycles in different combinations.