Synthesis and biological activities of new 1H‐1,2,4‐triazole alcohol derivatives containing a ferrocenyl moiety

Fourteen new 1H‐1,2,4‐triazole alcohol derivatives containing a ferrocenyl moiety were synthesized. In addition, six unexpected compounds, the hydroxyls of the title compounds, methylated by methanol, were obtained. The structures of all these new compounds were confirmed using ¹H NMR spectra, ¹³C NMR, MS and elemental analyses. Some compounds were also confirmed with IR spectra. The antifungal and plant growth regulatory activities of the title compounds are discussed. Copyright © 2008 John Wiley & Sons, Ltd.     

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, structure and biological activity of 1-(1-methoxy-1-ferrocenyl-3-arylpropan-2-yl)-1H-1,2,4-triazole derivatives

A total of eleven new 1-(1-methoxy-1-ferrocenyl-3-arylpropan-2-yl)-1H-1,2,4-triazole derivatives have been synthesized from acetylferrocene. The structures of the title compounds have been determined by elemental analysis, ¹H-NMR and single crystal X-ray diffraction analysis. Bioassay showed that some of the title compounds had high plant-growth regulatory activity. __________ Translated from Chinese Journal of Organic Chemistry, 2005, 25(8) (in Chinese)     

Synthesis and characterization of biologically active new Schiff bases containing 3‐functionalized 1,2,4‐triazoles and their zinc(II) complexes: crystal structure of 4‐bromo‐2‐[(E)‐(1H‐1,2,4‐triazol‐3‐ylimino)‐ methyl]phenol

Biologically active triazole Schiff bases ( L ¹  L ³ ) derived from the reaction of 3‐amino‐1,2,4‐triazole with chloro‐, bromo‐ and nitro‐ substituted salicylaldehydes and their Zn(II) complexes (1–3) have been synthesized and characterized by their physical, spectral and analytical data. Triazole Schiff bases potentially act as tridentate ligands and coordinate with the Zn(II) metal atom through salicylidene‐O, azomethine‐N and triazole‐N. The complexes have the general formula [M(L‐H)₂], where M = zinc(II) and L = ( L ¹ – L ³ ), and observe an octahedral geometry. The Schiff bases and their Zn(II) complexes have been screened for in‐vitro antibacterial, antifungal and brine shrimp bioassay. The biological activity data show the Zn(II) complexes to be more potent antibacterial and antifungal than the parent simple Schiff bases. Copyright © 2011 John Wiley & Sons, Ltd.     

A new three‐dimensional zinc(II) coordination polymer involving 2‐[(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1H‐benzimidazole and benzene‐1,4‐dicarboxylate ligands

Metal–organic frameworks (MOFs) based on multidentate N‐heterocyclic ligands involving imidazole, triazole, tetrazole, benzimidazole, benzotriazole or pyridine present intriguing molecular topologies and have potential applications in ion exchange, magnetism, gas sorption and storage, catalysis, optics and biomedicine. The 2‐[(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1H‐benzimidazole (tmb) ligand has four potential N‐atom donors and can act in monodentate, chelating, bridging and tridentate coordination modes in the construction of complexes, and can also act as both a hydrogen‐bond donor and acceptor. In addition, the tmb ligand can adopt different coordination conformations, resulting in complexes with helical structures due to the presence of the flexible methylene spacer. A new three‐dimensional coordination polymer, poly[[bis(μ₂‐benzene‐1,4‐dicarboxylato)‐κ⁴O¹,O^1′:O⁴,O^4′;κ²O¹:O⁴‐bis{μ₂‐2‐[(1H‐1,2,4‐triazol‐1‐yl)methyl‐κN⁴]‐1H‐benzimidazole‐κN³}dizinc(II)] trihydrate], {[Zn(C₈H₄O₄)(C₁₀H₉N₅)]·1.5H₂O}_n, has been synthesized by the reaction of ZnCl₂ with tmb and benzene‐1,4‐dicarboxylic acid (H₂bdic) under solvothermal conditions. There are two crystallographically distinct bdic²⁻ ligands [bdic²⁻(A) and bdic²⁻(B)] in the structure which adopt different coordination modes. The Zn^II ions are bridged by tmb ligands, leading to one‐dimensional helical chains with different handedness, and adjacent helices are linked by bdic²⁻(A) ligands, forming a two‐dimensional network structure. The two‐dimensional layers are further connected by bdic²⁻(B) ligands, resulting in a three‐dimensional framework with the topological notation 6⁶. The IR spectra and thermogravimetric curves are consistent with the results of the X‐ray crystal structure analysis and the title polymer exhibits good fluorescence in the solid state at room temperature.     

A Novel and Efficient Synthesis of 3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐ones (=3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐1‐benzopyran‐2‐ones)

An efficient one‐pot synthesis of 3‐[(4,5‐dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐one (=3‐[(4,5‐dihydro‐1H‐pyrrol‐3yl)carbonyl]‐2H‐1‐benzopyran‐2‐one) derivatives 4 by a four‐component reaction of a salicylaldehyde 1 , 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one, a benzylamine 2 , and a diaroylacetylene (=1,4‐diarylbut‐2‐yne‐1,4‐dione) 3 in EtOH is reported. This new protocol has the advantages of high yields (Table), and convenient operation. The structures of these coumarin (=2H‐1‐benzopyran‐2‐one) derivatives, which are important compounds in organic chemistry, were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).     

Preparation,characterization and biological activities of novel ferrocenyl‐substituted azaheterocycle compounds

α‐Haloacetylferrocene and α‐triazolylacetylferrocene have been prepared from acetylferrocene and they have proved to be useful building blocks for the synthesis of ferrocenyl propenone. Two new types of ferrocenyl vinyl triazole compound, (Z,E)‐ferrocenyl‐[1‐(1,2,4‐triazol‐1‐yl)‐2‐phenyl]‐vinyl‐ones, have been synthesized and their structures characterized by crystal X‐ray diffraction analysis. It has been shown for the first time that ferrocene, as an organometallic compound, has been introduced into bioactive triazole compounds in search of potent bioactive substances. Their biological activities are also discussed. Copyright © 2003 John Wiley & Sons, Ltd.     

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.     

Crystal structure,thermal behaviour and detonation characterization of bis(4,5‐diamino‐1,2,4‐triazol‐3‐yl)methane monohydrate

Bis(4,5‐diamino‐1,2,4‐triazol‐3‐yl)methane monohydrate (BDATZM·H₂O or C₅H₁₀N₁₀·H₂O) was synthesized and its crystal structure characterized by single‐crystal X‐ray diffraction; it belongs to the space group P (triclinic) with Z = 2. The structure of BDATZM·H₂O can be described as a two‐dimensional ladder plane with extensive hydrogen bonding and no disorder. The thermal behaviour was studied under non‐isothermal conditions by differential scanning calorimetry (DSC) and thermogravimetric/differential thermogravimetric (TG/DTG) methods. The detonation velocity (D) and detonation pressure (P) of BDATZM were estimated using the nitrogen equivalent equation according to the experimental density. A comparison between BDATZM·H₂O and bis(5‐amino‐1,2,4‐triazol‐3‐yl)methane (BATZM) was made to determine the effect of the amino group; the results suggest that the amino group increases the hydrophilicity, space utilization and energy, and decreases the thermal stability and symmetry of the resulting compound.     

Crystal structure,thermodynamic properties and detonation characterization of bis(5‐amino‐1,2,4‐triazol‐3‐yl)methane

Bis(5‐amino‐1,2,4‐triazol‐3‐yl)methane (BATZM, C₅H₈N₈) was synthesized and its crystal structure characterized by single‐crystal X‐ray diffraction; it belongs to the space group Fdd2 (orthorhombic) with Z = 8. The structure of BATZM can be described as a V‐shaped molecule with reasonable chemical geometry and no disorder. The specific molar heat capacity (C_p,m) of BATZM was determined using the continuous C_p mode of a microcalorimeter and theoretical calculations, and the C_p,m value is 211.19 J K^?1 mol^?1 at 298.15 K. The relative deviations between the theoretical and experimental values of C_p,m, H_T – H_298.15K and S_T – S_298.15K of BATZM are almost equivalent at each temperature. The detonation velocity (D) and detonation pressure (P) of BATZM were estimated using the nitrogen equivalent equation according to the experimental density; BATZM has a higher detonation velocity (7954.87 ± 3.29 m s^?1) and detonation pressure (25.72 ± 0.03 GPa) than TNT.     

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.     

A new one‐dimensional ZnII coordination polymer based on 2‐[(1H‐imidazol‐1‐yl)methyl]‐1H‐benzimidazole and benzene‐1,2‐dicarboxylate

Multidentate N‐heterocyclic compounds form a variety of metal complexes with many intriguing structures and interesting properties. The title coordination polymer, catena‐poly[zinc(II)‐bis{μ‐2‐[(1H‐imidazol‐1‐yl)methyl]‐1H‐benzimidazole}‐κ²N³:N^3′;N^3′:N³‐zinc(II)‐bis(μ‐benzene‐1,2‐dicarboxylato)‐κ²O¹:O²;κ³O¹,O^1′:O²], [Zn₂(C₈H₄O₄)₂(C₁₁H₁₀N₄)₂]_n, has been synthesized by the reaction of Zn(NO₃)₂ with 2‐[(1H‐imidazol‐1‐yl)methyl]‐1H‐benzimidazole (imb) and benzene‐1,2‐dicarboxylic acid (H₂bdic) under hydrothermal conditions. There are two crystallographically distinct imb ligands [imb(A) and imb(B)] in the structure which adopt very similar coordination geometries. The imb(A) ligand bridges two symmetry‐related Zn1 ions, yielding a binuclear [(Zn1)₂{imb(A)}₂] unit, and the imb(B) ligand bridges two symmetry‐related Zn2 ions resulting in a binuclear [(Zn2)₂{imb(B)}₂] unit. The above‐mentioned binuclear units are further connected alternately by pairs of bridging bdic²⁻ ligands, forming an infinite one‐dimensional chain. These one‐dimensional chains are further connected through N—H...O hydrogen bonds, leading to a two‐dimensional layered structure. In addition, the title polymer exhibits good fluorescence properties in the solid state at room temperature.     

Design,Synthesis and Biological Evaluation of Isothiazole Based 1,2,4‐Trizaole Derivatives

A series of novel 3,4‐dichloroisothiazole based 1,2,4‐triazole derivatives were rationally designed and synthesized. Their structures were confirmed by ¹H NMR, ¹³C NMR, HRMS or elemental analysis; the typical crystal structure was determined by X‐ray diffraction for validation. All target compounds were evaluated for their in vitro fungicidal and in vivo anti‐TMV activities. The bioassay results indicated that compound 6b , namely 1‐(3,4‐dichloroisothiazol‐5‐yl)‐1‐(4‐fluorophenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethanol, exhibited excellent growth inhibition against B. cinerea, C. arachidicola and P. piricola with median effective concentrations (EC₅₀) of 6.98, 2.73 and 3.07 μg/mL, respectively, and good in vivo anti‐TMV activity of over 60% of inactivation and induction activity at 100 μg/mL. These data demonstrate that compound 6b is both a fungicide and an anti‐TMV lead, deserving further studies.     

A new one‐dimensional CdII coordination polymer with a two‐dimensional layered structure incorporating 2‐[(1H‐imidazol‐1‐yl)methyl]‐1H‐benzimidazole and benzene‐1,2‐dicarboxylate ligands

The N‐heterocyclic ligand 2‐[(1H‐imidazol‐1‐yl)methyl]‐1H‐benzimidazole (imb) has a rich variety of coordination modes and can lead to polymers with intriguing structures and interesting properties. In the coordination polymer catena‐poly[[cadmium(II)‐bis[μ‐benzene‐1,2‐dicarboxylato‐κ⁴O¹,O^1′:O²,O^2′]‐cadmium(II)‐bis{μ‐2‐[(1H‐imidazol‐1‐yl)methyl]‐1H‐benzimidazole}‐κ²N²:N³;κ²N³:N²] dimethylformamide disolvate], {[Cd(C₈H₄O₄)(C₁₁H₁₀N₄)]·C₃H₇NO}_n, (I), each Cd^II ion exhibits an irregular octahedral CdO₄N₂ coordination geometry and is coordinated by four O atoms from two symmetry‐related benzene‐1,2‐dicarboxylate (1,2‐bdic²⁻) ligands and two N atoms from two symmetry‐related imb ligands. Two Cd^II ions are connected by two benzene‐1,2‐dicarboxylate ligands to generate a binuclear [Cd₂(1,2‐bdic)₂] unit. The binuclear units are further connected into a one‐dimensional chain by pairs of bridging imb ligands. These one‐dimensional chains are further connected through N—H…O hydrogen bonds and π–π interactions, leading to a two‐dimensional layered structure. The dimethylformamide solvent molecules are organized in dimeric pairs via weak interactions. In addition, the title polymer exhibits good fluorescence properties in the solid state at room temperature.     

Synthesis and crystal structure of a two‐dimensional sodium coordination polymer of 4,4′‐(diazenediyl)bis(1H‐1,2,4‐triazol‐5‐one)

The crystal engineering of coordination polymers has aroused interest due to their structural versatility, unique properties and applications in different areas of science. The selection of appropriate ligands as building blocks is critical in order to afford a range of topologies. Alkali metal cations are known for their mainly ionic chemistry in aqueous media. Their coordination number varies depending on the size of the binding partners, and on the electrostatic interaction between the ligands and the metal ions. The two‐dimensional coordination polymer poly[tetra‐μ‐aqua‐[μ₄‐4,4′‐(diazenediyl)bis(5‐oxo‐1H‐1,2,4‐triazolido)]disodium(I)], [Na₂(C₄H₂N₈O₂)(H₂O)₄]_n, (I), was synthesized from 4‐amino‐1H‐1,2,4‐triazol‐5(4H)‐one (ATO) and its single‐crystal structure determined. The mid‐point of the imino N=N bond of the 4,4′‐(diazenediyl)bis(5‐oxo‐1H‐1,2,4‐triazolide) (ZTO²⁻) ligand is located on an inversion centre. The asymmetric unit consists of one Na⁺ cation, half a bridging ZTO²⁻ ligand and two bridging water ligands. Each Na⁺ cation is coordinated in a trigonal antiprismatic fashion by six O atoms, i.e. two from two ZTO²⁻ ligands and the remaining four from bridging water ligands. The Na⁺ cation is located near a glide plane, thus the two bridging O atoms from the two coordinating ZTO²⁻ ligands are on adjacent apices of the trigonal antiprism, rather than being in an anti configuration. All water and ZTO²⁻ ligands act as bridging ligands between metal centres. Each Na⁺ metal centre is bridged to a neigbouring Na⁺ cation by two water molecules to give a one‐dimensional [Na(H₂O)₂]_n chain. The organic ZTO²⁻ ligand, an O atom of which also bridges the same pair of Na⁺ cations, then crosslinks these [Na(H₂O)₂]_n chains to form two‐dimensional sheets. The two‐dimensional sheets are further connected by intermolecular hydrogen bonds, giving rise to a stabile hydrogen‐bonded network.     

Synthesis,Characterization and Crystal Structure of the Dimeric Silver(I) Complex containing 4‐Amino‐5‐methyl‐2H‐1,2,4‐triazole‐3(4H)‐thione

The reaction of 4‐amino‐5‐methyl‐2H‐1,2,4‐triazole‐3(4H)‐thione (AMTT, 1 ) with AgNO₃ and triphenylphosphane in a molar ratio 1:1:2 in ethanol led to the dimeric complex {[Ag(AMTT)(PPh₃)₂]NO₃}₂·4EtOH ( 2 ). 2 was characterized by elemental analyses, IR, ³¹P NMR spectroscopy as well as single crystal X‐ray diffraction. Crystal data for 2 at ?80 °C: space group with a = 1265.5(2), b = 1300.9(2), c = 1509.5(2) pm, α = 83.77(2)°, β = 79.22(2)°, γ = 62.89(2)°, Z = 2, R₁ = 0.0330.     

Synthesis, Crystal Structure and Biological Activities of O, O-Dialkyl α-[1-（2-Chlorothiazol-5-ylmethyl）-5-methyl- 1 H-1,2,3-triazol-4-ylcarbonyloxy]alkylphosphonates

In order to search for novel agrochemicals with high activity and low toxicity, a series of phosphonate derivatives containing 1,2,3-triazole and thiazole rings were designed and synthesized using 2-chloro-5-（chloromethyl）- thiazole as the starting material. Their structures were confirmed by IR, ^1H NMR, ^31p NMR, EI-MS or ESI-MS and elemental analyses. The crystal structure of 7a was determined by single crystal X-ray diffraction. Preliminary bioassays indicated that most of the target compounds did not display insecticidal activities, but a fraction of them possessed herbicidal and fungicidal activities to some extent.     

Poly[[{μ4‐3‐[(1H‐1,2,4‐triazol‐1‐yl)methyl]benzoato}zinc(II)] hemihydrate]: a novel two‐dimensional framework formed by self‐association of zinc(II) sulfate with 3‐[(1H‐1,2,4‐triazol‐1‐yl)methyl]benzoic acid

The title novel two‐dimensional coordination polymer, {[Zn₂(C₁₀H₈N₃O₂)₄]·H₂O}_n, features a {Zn₂L₂} bimetallic ring repeat unit {L is the 3‐[(1H‐1,2,4‐triazol‐1‐yl)methyl]benzoate ligand}. Each Zn^II cation of the bimetallic ring is further bonded to two other L ligands, resulting in a novel infinite two‐dimensional network structure with two channels of different sizes. The crystallographically unique Zn^II atom is thus six‐coordinated in a distorted octahedral environment of four carboxylate O atoms and two triazole N atoms. Two of these networks interpenetrate in an orthogonal arrangement to form the full three‐dimensional framework, with disordered water molecules located in the channels.     

Three polymorphs of 3‐(3‐phenyl‐1H‐1,2,4‐triazol‐5‐yl)‐2H‐1‐benzopyran‐2‐one formed from different solvents

The polymorphic study of 3‐(3‐phenyl‐1H‐1,2,4‐triazol‐5‐yl)‐2H‐1‐benzopyran‐2‐one, C₁₇H₁₁N₃O₂, was performed due to its potential biological activity and revealed three polymorphic modifications in the triclinic space group P, the monoclinic space group P2₁ and the orthorhombic space group Pbca. These polymorphs have a one‐column layered type of crystal organization. The strongest interactions between the molecules of the studied structures is stacking between π‐systems, while N—H…N and C—H…O hydrogen bonds link stacked columns forming layers as a secondary basic structural motif. C—H…π hydrogen bonds were observed between neighbouring layers and their role is the least significant in the formation of the crystal structure. Packing differences between the polymorphic modifications are minor and can be identified only using an analysis based on a comparison of the pairwise interaction energies.     

Synthesis and Antiproliferative Activity of 6‐Ferrocenyl‐3‐Substituted 7H‐1,2,4‐Triazolo[3, 4‐b]‐1,3,4‐Thiadiazines

Five new 6‐ferrocenyl‐3‐substituted 7H‐1,2,4‐triazolo[3, 4‐b]‐1,3,4‐thiadiazines ( 3a‐e ) have been synthesized and characterized on the basis of elemental analyses and spectral data. The antiproliferative activities were examined in two human cell lines (BJ and HT 1080) with the acid phosphatase assay. The results showed that all compounds could reduce cell viability. The significant difference between the two cell lines was that fibrosarcoma HT 1080 cells could indeed be more susceptible to the compounds than the normal fibroblast BJ cells.