Efficient synthesis and characterization of novel bis-heterocyclic derivatives and benzo-fused macrocycles containing oxazolone or imidazolone subunits

Bis(3-(arylthiomethyl)benzaldehydes), linked to aliphatic spacers via ethers, were prepared and used as key synthons for the bis(2-phenyloxazol-5(4H)-ones) via their reaction with benzoylglycine in acetic anhydride in the presence of fused sodium acetate at 100°C for 6 hours. Bis(oxazol-5(4H)-ones) were reacted with the appropriate aromatic or heterocyclic amines in glacial acetic acid in the presence of fused sodium acetate at 100°C for 24 hours to afford a novel series of bis(2-phenylimidazol-4-ones) and their related hybrids with benzo[d]thiazole and pyrimidine-2,4(1H,3H)-dione. Moreover, bis(oxazol-5(4H)-ones) reacted with (4-aminobenzoyl)glycine to afford bis[(4-(5-oxo-1H-imidazol-1-yl)benzoyl)glycine] derivatives followed by their reaction with anisaldehyde in acetic anhydride containing fused sodium acetate at 100°C for 12 hours to afford bis(5-oxo-1H-imidazol-1-yloxazol-5(4H)-one) hybrids. Furthermore, bis(3-(arylthiomethyl)benzaldehydes) were reacted with 2,2′-(terephthaloylbis(azanediyl))diacetic acid in acetic anhydride containing fused sodium acetate at 100°C for 12 hours to give benzo-fused macrocycles containing oxazolone subunits which reacted with appropriate aromatic amines in DMF and glacial acetic acid containing fused sodium acetate at 100°C for 24 hours to give benzo-fused macrocycles containing imidazolone subunits.     

Synthesis and Antioxidant Activity of Bis (Aroyl/Arylsulfonyl Ethenesulfonylmethylazolyl)Pyridines

A new class of 2,6‐pyridine linked bis (oxadiazoles), bis (thiadiazoles), and bis (triazoles) were prepared from the synthetic intermediates pyridine‐2,6‐dicarbohydrazide, E‐aroylethenesulfonylacetic acid and E‐arylsulfonylethenesulfonylacetic acid adopting ultrasonication methodology and tested for their antioxidant activity. Among all the tested compounds 2,6‐(bis (2‐(4‐methylbenzoylethenesulfonylmethyl)‐1,3,4‐oxadiazol‐5‐yl))‐pyridine ( 7b ) was found to be potential antioxidant agent.     

Bis(nitro- and polynitromethyl-ONN-azoxy)azoxyfurazans and some of their derivatives

Reaction of diamino derivative of azoxyfurazan with 2,2-dimethyl-5-nitro-5-nitroso-1,3-dioxane in the presence of dibromoisocyanuric acid afforded bis(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl-ONN-azoxy)azoxyfurazan. The reaction of the latter with AcCl/MeOH and further transformations of the product gave the first representative of substituted (mono- and polynitroalkyl-ONN-azoxy)azoxyfurazans, e.g. bis(nitromethyl-ONN-azoxy)azoxyfurazan, bis(dinitromethyl-ONN-azoxy)azoxyfurazan, bis(trinitromethyl-ONN-azoxy)azoxyfurazan, and some of their derivatives.     

Different supramolecular interactions mediated by Br atoms in the crystal structures of three anisole derivatives

Three anisole building blocks featuring bis(hydroxymethyl) or bis(bromomethyl) pendants have been analyzed with regard to their molecular structures and packing behaviour. The compounds are ethyl 3,5‐bis(hydroxymethyl)‐4‐methoxybenzoate, C₁₂H₁₆O₅, (I), [5‐bromo‐3‐(hydroxymethyl)‐2‐methoxyphenyl]methanol [or 4‐bromo‐2,6‐bis(hydroxymethyl)anisole], C₉H₁₁BrO₃, (II), and 5‐bromo‐1,3‐bis(bromomethyl)‐2‐methoxybenzene [or 4‐bromo‐2,6‐bis(bromomethyl)anisole], C₉H₉Br₃O, (III). A typical supramolecular pattern involved C—H…π interactions generating molecular stacks, while π–π interactions were only observed in the absence of bromine, indicating a striking influence on the distances between adjacent aromatic moieties. When comparing bis(hydroxymethyl) compound (II) with bis(bromomethyl) compound (III), we found that the strong O—H…O hydrogen bonds in a zigzag arrangement in the first are replaced by C—H…Br interactions in the second without a change in the general packing.     

双[N,N'-亚烃基-2,2'-(芳亚甲基)二(3,4-二甲基吡咯-5-醛缩亚胺)]合双锰(Ⅱ)的合成、光谱特征及拟酶催化性能研究

首次报道了新型Schif碱类配体双[N,N-亚烃基-2,2-(苯亚甲基)二(3,4-二甲基吡咯-5-醛缩亚胺)]和双[N,N-(1,2-亚乙基)-2,2-(4-甲氧基苯亚甲基)二(3,4-二甲基吡咯-5-醛缩亚胺)]及其双锰配合物的合成方法、光谱特征及用配合物催化PhIO单加氧化环己烷反应的研究。     

Energetic Materials with Promising Properties: Synthesis and Characterization of 4,4′‐Bis(5‐nitro‐1,2,3‐2H‐triazole) Derivatives

Using a variety of functionalization strategies, derivatives of 4, 4′‐bis(5‐nitro‐1,2,3‐2H‐triazole) were designed, synthesized, and characterized. The isomers were separated, their structures were confirmed with single‐crystal X‐ray analysis, and their properties were determined by differential scanning calorimetry, density, impact sensitivity, heat of formation, and detonation velocity and pressure (calculated by EXPLO5 V6.01). Those materials were found to exhibit superior detonation performance when compared with the other fully carbon‐nitrated bis(azoles).     

Novel soluble thermally stable silane-containing aromatic polyimides with reduced dielectric constant

Bis(p-aminophenoxy)diphenylsilane (BPS), bis(m-aminophenoxy)diphenylsilane (BMS) and bis(5-amino-1-naphthoxy)diphenylsilane (BAS) as three silane-diamines were prepared by the reactions of 4-aminophenol, 3-aminophenol, and 5-amino-1-naphthol respectively, with dichlorodiphenylsilane in the presence of triethylamine. The related silane-containing polyimides were prepared by two-step polycondensation reactions of these diamines with three different aromatic dianhydrides. All the polymers were characterized and their physical and thermal properties were studied. The polymers showed high thermal stability while their solubility was greatly increased in polar aprotic solvents. Wide angle X-ray diffraction showed that all the polyimides were almost amorphous. Also their dielectric constants were decreased due to the incorporation of softening and low-polarizing siloxane units into the polymer backbone.     

Synthesis of Bicyclo[1.1.1]pentane Bioisosteres of Internal Alkynes and para‐Disubstituted Benzenes from [1.1.1]Propellane

We report a general preparation of arylated bicyclo[1.1.1]pentanes through the opening of [1.1.1]propellane with various arylmagnesium halides. After transmetalation with ZnCl₂ and Negishi cross‐coupling with aryl and heteroaryl halides, bis‐arylated bicyclo[1.1.1]pentanes are obtained. These bis‐arylated bicyclo[1.1.1]pentanes may be considered as bioisosteres of internal alkynes. Bioisosteres of tazarotene and the metabotropic glutamate receptor 5 (mGluR5) antagonist 2‐methyl‐6‐(phenylethynyl)pyridine were prepared and their physicochemical properties were evaluated.     

Synthesis of novel scaffolds based on thiazole or triazolothiadiazine linked to benzofuran or benzo[d]thiazole moieties as new hybrid molecules

Abstract

A synthesis of novel hybrid molecules containing thiazole or bis(thiazoles) each bearing benzofuran and/or benzo[d]thiazole moieties by the reaction of the appropriate thioamide derivatives with the corresponding bis-bromoacetyl derivatives is reported. Mono- and bis(triazolothiadiazine) derivatives based on benzofuran or benzo[d]thiazole moieties were also synthesized in good yields by the reaction of the appropriate bis(bromoacetyl) derivatives with each of 4-amino-5-mercapto-1,2,4-triazoles and their corresponding bis-derivatives.     

Hydrolysis of Bis[5,5-dimethyl-3-(4-oxa-1-azoniacyclohexylidene)-1-cyclohexenyl] Sulfide Diperchlorate

Hydrolysis of bis[5,5-dimethyl-3-(4-oxa-1-azoniacyclohexylidene)-1-cyclohexenyl] sulfide diperchlorate, as well as of bis(5,5-dimethyl-3-thioxo-1-cyclohexenyl) sulfide, in the system MeCN-Et₃N yields a mixture of bis(5,5-dimethyl-3-oxo-1-cyclohexenyl) sulfide and isomeric 5,5-dimethyl-3-oxo-1-cyclohexenyl 3,3-dimethyl-5-oxo-1-cyclohexenyl sulfide. The structure of the products and their ratio were established by ¹H and ¹³C NMR and IR spectroscopy.     

Effect of central spacer chain structure on cationic cyclopolymerization tendency of divinyl ethers

To clarify the effects of the central spacer chain structure of divinyl ethers on their cationic cyclopolymerization tendencies, 1,4‐bis[(2‐vinyloxy)ethoxy]benzene ( 1 ), 1,4‐bis[(2‐vinyloxy)ethoxy]butane ( 2 ), 1,6‐bis[(2‐vinyloxy)ethoxy]hexane ( 3 ), 1,8‐bis[(2‐vinyloxy)ethoxy]octane ( 4 ), and 1,4‐bis[(4‐vinyloxy)butoxy]butane ( 5 ) were polymerized with the hydrogen chloride/zinc chloride (HCl/ZnCl₂) initiating system in methylene chloride (CH₂Cl₂) at 0 °C at low initial monomer concentration ([M]₀ = 0.15 M). The polymerizations of divinyl ethers 2 and 3 gave soluble polymers quantitatively. In contrast, the polymerizations of divinyl ethers 1 , 4 , and 5 underwent gel formation at high monomer conversion. The content of the unreacted vinyl groups of the obtained soluble polymers was measured by ¹H NMR spectroscopy. Judging from the relatively low vinyl contents of the polymers produced even in the early stage of the polymerization (monomer conversion < ～20%), the cyclopolymerization occurred to some extent for 2 , 3 , and 4 . On the contrary, the polymers produced from 1 and 5 exhibited the relatively high vinyl content, indicating that the cyclopolymerization tendencies of 1 and 5 were lower than those of 2 , 3 , and 4 . These results are discussed in terms of the structural variety of the spacer chains: (1) the presence of benzene ring ( 1 vs 2 ), (2) their length ( 2 vs 3 and 4 ), and (3) the position of ether oxygen ( 4 vs 5 ). © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4002–4012, 2002     

Synthesis of Bis{(S‐methyl)azolespoly(ethylene oxide)} from 3,6‐dioxa‐1,8‐octanedithiol

Bis(1,3,4‐oxadiazoles) 4 , 5 and bis(1,2,4‐triazoles) 6a , 6b have been prepared from 3,6‐dioxa‐1,8‐octanedithiol 1 through a multistep reaction sequence. Compound 4 reacted with the appropriate alkyl halide in the presence of potassium carbonate in refluxing acetone to give the corresponding bis(S‐alkylated‐1,3,4‐oxadiazoles) 7a , 7b . The title compound 8 was prepared by condensing 4 with benzoyl bromide in the presence of triethylamine. Further, 6,9‐dioxa‐3,12‐dithiotetradecanedihydrazide 3 was converted to bis{N′‐(phenylaminocarbonyl) hydrazides} and bis{N′‐(phenylaminocarbonothioyl)hydrazides} 9a , 9b using phenylisocyanate and phenylthioisocyanate, respectively, which underwent cyclization in alkaline medium to produce 6,9‐dioxa‐3,12‐dithiotetradecane bis(4‐phenyl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐one) and their 3‐thio analogs 10a , 10b . The new compounds 4 , 5 , 6 , 7 , 8 , 9 , 10 were characterized by their IR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analyses.     

Synthesis and properties of novel triptycene‐based polyimides

Two new triptycene‐containing bis(ether amine)s, 1,4‐bis(4‐aminophenoxy)triptycene ( 4 ) and 1,4‐bis(4‐amino‐2‐trifluoromethylphenoxy)triptycene ( 6 ), were synthesized, respectively, from the nucleophilic chloro‐displacement reactions of p‐chloronitrobenzene and 2‐chloro‐5‐nitrobenzotrifluoride with 1,4‐dihydroxytriptycene in the presence of potassium carbonate, followed by palladium‐catalyzed hydrazine reduction of the dinitro intermediates. The bis(ether amine)s were polymerized with six commercially available aromatic tetracarboxylic dianhydrides to obtain two series of novel triptycene‐based polyimides 8a – f and 9a – f by using a conventional two‐step synthetic method via thermal and chemical imidizations. All the resulting polyimides exhibited high enough molecular weights to permit the casting of flexible and strong films with good mechanical properties. Incorporation of trifluoromethyl groups in the polyimide backbones improves their solubility and decreases their dielectric constants. The fluorinated polyimides 9d and 9f derived from diamine 6 with 4,4′‐oxydiphthalic anhydride and 2,2‐bis(3,4‐dicarboxyphenyl)hexafluoropropane dianhydride (6FDA), respectively, could afford almost colorless thin films. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

From Phosphate to Bis(methylene) Sulfone: Non‐Ionic Backbone Linkers in DNA

Chimeric DNA molecules containing four different linking groups, the natural phosphate, 5′‐methylenephosphonate, bis(methylene)phosphinate, and bis(methylene) sulfone (see Fig. 1), were directly compared for their ability to form duplexes with complementary DNA and DNA chimeras. From melting temperatures for analogous complementary sequences, general conclusions about the impact of geometric distortion of the internucleotide linkage around the two P O C bridges were drawn, as were conclusions about the impact on duplex stability that arises from the removal of the negative charge in the linking group. Each structural perturbation diminished the melting temperature, by ca. −2.5° per modification for the 5′‐methylenephosphonate, −3.5° per modification for the bis(methylene)phosphinate, and −4.5° per modification for the bis(methylene) sulfone linker. These results have implications for DNA chemistry including the design of ‘antisense' candidates and the proposal of alternative genetic materials in the search for non‐terrean life.     

Nano silver particles catalyzed synthesis,molecular docking and bioactivity of α-thiazolyl aminomethylene bisphosphonates

Abstract

A new series of α-thiazolyl aminomethylene bisphosphonates were synthesized by a three component reaction of 4-aryl substituted thiazol-2-amine with different dialkyl/aryl phosphites and triethyl orthoformate in the presence of Ag NPs (nano particles) as a catalyst under solvent free conditions. All the synthesized target compounds were characterized by ¹H, ¹³C, ³¹P, mass and elemental analysis. The target compounds were screened for their in vitro antioxidant, antibacterial and antifungal activity. Molecular docking studies were also performed. The results revealed that among the synthesized compounds tetramethyl(((4-(4-methoxyphenyl)thiazol-2-yl)amino) methylene)bis(phosphonate) (5d), tetramethyl(((4-(4-fluorophenyl)thiazol-2-yl)amino) methylene) bis(phosphonate) (5h), and tetramethyl(((4-(4-bromophenyl)thiazol-2-yl)amino)methylene) bis (phosphonate) (5j) showed remarkably higher antioxidant activity by DPPH and H₂O₂ than the standard ascorbic acid. Compounds tetramethyl(((4-phenyl thiazol-2-yl)amino) methylene) bis(phosphonate) (5a), 5d, 5h and tetraethyl(((4-(4-bromophenyl)thiazol-2-yl) amino)methylene)bis (phosphonate) (5k) showed good antibacterial activity. 5a, 5d, and 5h also showed rather higher antifungal activity than the standard flucanozole. Computational docking methods have been used to predict how several aminomethylene bisphosphonate derivatives compete against the inhibitor BPH-1330 at the crystal enzyme structure of the 4H3A protein active site and how R and R₁ influence their binding ability.     

Novel polyurethanes with macroheterocyclic (crown-ether) structures in the polymer backbone

The synthesis of a functionalized crown ether was accomplished in two steps by condensing 3,4-dihydroxybenzaldehyde with bis(2-chloroethyl)ether and subsequent reduction of the reaction product, bis(formylbenzo)-18-crown-6 (4) to a diol (5). Polyurethanes that bear the dibenzo-18-crown-6 moiety in the polymer backbone were synthesized from bis(methylolbenzo)-18-crown-6 (5), a polypropylene glycol, and methylene bis(4-cyclohexyl isocyanate). The resulting polymers were fibrous white solids with glass transitions from ca. 15–120°C, depending on the starting diol composition. The thermomechanical spectra of melt pressed or solvent cast films of several crown-ether-bearing polyurethanes showed evidence of multiphase character. The polymers failed to complex effectively with sodium ions. However, their complexing ability with potassium ion was similar in magnitude to that observed with relatively simple crown ethers.     

Molecular structures of a series of substituted bis(η5‐cyclopentadienyl)titanium dihalides CpR2TiX2 [X = F,Cl, Br and I; R = CHPh2, CH(p‐Tol)2 and adamantyl]

Metallocene dihalides and derivatives thereof are of great interest as precursors for catalysts in polymerization reactions, as antitumor agents and, due to their increased stability, as suitable starting materials in salt metathesis reactions and the generation of metallocene fragments. We report the synthesis and structural characterization of a series of eleven substituted bis(η⁵‐cyclopentadienyl)titanium dihalides, namely bis[η⁵‐1‐(diphenylmethyl)cyclopentadienyl]difluoridotitanium(IV), [Ti(C₁₈H₁₅)₂F₂], bis{η⁵‐1‐[bis(4‐methylphenyl)methyl]cyclopentadienyl}difluoridotitanium(IV), [Ti(C₂₀H₁₉)₂F₂], and bis{η⁵‐1‐[bis(adamantan‐2‐yl)methyl]cyclopentadienyl}difluoridotitanium(IV), [Ti(C₁₅H₁₉)₂F₂], together with the bromide and iodide analogues, and the chloride analogues of the diphenylmethyl and adamantyl complexes. These eleven complexes were prepared by the reaction of the corresponding bis(η⁵:η¹‐pentafulvene)titanium complexes with different hydrogen halides (Cl, Br and I). The titanocene fluorides become available via chloride–fluoride exchange reactions.     

Synthesis of New Phosphines and P-Heterocycles from Phosphonates Containing Allyl Group

Addition of phenylphosphine to allylphosphonate followed by reduction of the resulting diphosphonate gives a new branched phosphine, bis(3-phosphinopropyl)phenylphosphine. Its reaction with paraform and p-toluidine yields oligomeric 3-[3-(propylenophenylphosphino)propyl]-1,5-di-p-tolyl-1,5,3,7-diazadiphosphacyclooctane. Diethyl (5-allyl-2-ethoxybenzyl)phosphonate was obtained. Its reduction gives unsaturated (5-allyl-2-ethoxybenzyl)phosphine. This product adds two moles of formaldehyde to give bis(hydroxymethyl)(5-allyl-2-ethoxybenzyl)phosphine. The reaction of this compound with p-toluidine yielded, depending on the conditions, the corresponding bis(aminomethyl)phosphine, 1,3,5-diazaphosphorinane, and 1,5,3,7-diazadiphosphacyclooctane, and also their derivatives containing allyl substituents.     

Chemotherapeutic agents. IX. Synthesis and pesticidal activities of bis[4-aryl/alkyl-1, 2, 4-triazoline-5-thione-3-yl]alkanes and 1 -Aryl/alkyl-3-[4-(4-aryl/alkyl-1, 2, 4-triazoline-5-thione-3-yl)phenyl]thiourea and related compounds

Various bis[4-aryl/alkyl-1, 2, 4-triazoline-5-thione-3-yl]alkanes ( 3 ) were prepared from base cyclization of bis thiosemicarbazide 2 and transformed into sulphides by reaction with different alkyl halides in alkaline medium. These compounds were further oxidised to sulphones 5 with acidic potassium permanganate. 1-Aryl-3-[4-(4-aryl/alkyl-1, 2, 4-triazoline-3-thione-5-yl)phenyl]thioureas ( 8 ) were prepared in two steps from p-aminophenylhydrazide ( 6 ) and aryl/alkylisothiocyanates. Alkylation of 8 with different alkyl halides yielded exclusively sulphides 9 . Some sulphides 12 and Mannich bases 13 from 5-(p-fluorophenyl)-1, 3, 4-oxadiazol-2-thione ( 11 ) were also prepared to evaluate their pesticidal activities. All the prepared compounds were screened for pesticidal activities but none of them exhibited any significant activity.     

Synthesis and Spectroscopic Characterization of Some Ferrocenyl Schiff Bases Containing Pyridine Moiety and Their Complexation with Cobalt,Nickel, Copper and Zinc

Three novel ferrocenyl Schiff base ligands containing pyridine moiety have been formed by 1:2 molar condensation of 1,1′‐diacetylferrocene with 2‐aminopyridine, 2‐amino‐5‐picoline or 2‐amino‐5‐chloropyridine, respectively. The ligands are 1,1′‐bis[1‐(pyridyl‐2‐imino)‐ethyl]ferrocene (L1); 1,1′‐bis[1‐(5‐methyl‐pyridyl‐2‐imino)ethyl]ferrocene (L2) and 1,1′‐bis[1‐(5‐chloropyridyl‐2‐imino)ethyl]ferrocene (L3). These ligands form 1:1 complexes with Co(II), Cu(II), Ni(II) and Zn(II) ions. The prepared ligands and their complexes have been characterized by IR, ¹H NMR, ¹³C NMR, UV/Vis spectra as well as elemental analysis. The spectral data of the ligands and their complexes are discussed in connection with the structural changes due to complexation.