Synthesis and Cytotoxic Evaluation of Novel 1,2,3‐Triazole‐4‐Linked (2E,6E)‐2‐Benzylidene‐6‐(4‐nitrobenzylidene)cyclohexanones

This work describes the synthesis of novel 1,2,3‐triazole‐4‐linked (2E,6E)‐2‐benzylidene‐6‐(4‐nitrobenzylidene)cyclo‐hexanones starting from cyclohexanone. 1‐(Cyclohex‐1‐en‐1‐yl)piperidine, the enamine from cyclohexanone and piperidine, reacted with 4‐nitrobenzaldehyde to obtain 2‐(4‐nitrobenzylidene)cyclohexanone. Condensation of the latter compound with (prop‐2‐yn‐1‐yloxy)benzaldehyde derivatives under acidic conditions gave (4‐nitrobenzylidene)‐[(prop‐2‐yn‐1‐yloxy)‐benzylidene]cyclohexanones. Finally, ‘click reaction’ of these derivatives and various organic azides led to the title compounds. All compounds were examined by MTT assay for cytotoxic activity in one human breast cancer cell line, MDA‐MB‐231.     

Synthesis and Antibacterial Activity of Novel (4‐Fluorophenyl)(4‐(naphthalen‐2‐yl)‐6‐aryl‐2‐thioxo‐2,3‐dihydropyrimidin‐1(6H)‐yl)methanone Derivatives

A novel series of (4‐fluorophenyl)(4‐(naphthalen‐2‐yl)‐6‐aryl‐2‐thioxo‐2,3‐dihydropyrimidin‐1(6H)‐yl)methanone derivatives were synthesized from reaction of 6‐(naphthalen‐2‐yl)‐4‐aryl‐3,4‐dihydropyrimidine‐2(1H)‐thiones with 4‐fluorobenzoylchloride in dichloromethane in the presence of triethylamine. The synthesized compounds were screened for antibacterial activity against Gram positive bacteria, namely, Staphylococcus aureus ATCC25923 and Listeria monocytogenes MTCC657, and Gram negative bacteria, namely, Escherichia coli ATCC25922 and Klebsiella pneumoniae ATCC700603, respectively. Some of the tested compounds showed significant antimicrobial activity.     

Zur Umsetzung von Kupfer(I)‐ und Kupfer(II)‐Salzen mit P(C6H4CH2NMe2‐2)3 ‐ die Festkörperstrukturen von {[P(C6H4CH2NMe2‐2)3]CuOClO3}ClO4, {[P(C6H4CH2NMe2‐2)3]Cu}ClO4, [P(C6H4CH2NMe2‐2)3]CuONO2 und [P(C6H4CH2NMe2‐2)2(C6H4CH2NMe2H+NO3‐‐2)]CuONO2

Reaction Behaviour of Copper(I) and Copper(II) Salts Towards P(C₆H₄CH₂NMe₂‐2)₃ ‐ the Solid‐State Structures of {[P(C₆H₄CH₂NMe₂‐2)₃]CuOClO₃}ClO₄, {[P(C₆H₄CH₂NMe₂‐2)₃]Cu}ClO₄, [P(C₆H₄CH₂NMe₂‐2)₃]CuONO₂ and [P(C₆H₄CH₂NMe₂‐2)₂(C₆H₄CH₂NMe₂H⁺NO₃^‐‐2)]CuONO₂ The reaction behaviour of P(C₆H₄CH₂NMe₂‐2)₃ ( 1 ) towards different copper(II) and copper(I) salts of the type CuX₂ ( 2a : X = BF₄, 2b : X = PF₆, 2c : X = ClO₄, 2d : X = NO₃, 2e : X = Cl, 2f : X = Br, 13 : X = O₂CMe) and CuX ( 5a : X = ClO₄, 5b : X = NO₃, 5c : X = Cl, 5d : X = Br) is discussed. Depending on X, the transition metal complexes [P(C₆H₄CH₂NMe₂‐2)₃Cu]X₂ ( 3a : X = BF₄, 3b : X = PF₆), {[P(C₆H₄CH₂NMe₂‐2)₃]CuX}X ( 4 : X = ClO₄, 11a : X = Cl, 11b : X = Br, 14 : X = O₂CMe), {[P(C₆H₄CH₂NMe₂‐2)₃]Cu}ClO₄ ( 6 ), [P(C₆H₄CH₂NMe₂‐2)₃]CuX ( 7a : X = Cl, 7b : X = Br, 10 : X = ONO₂), [P(C₆H₄CH₂NMe₂‐2)₂(C₆H₄CH₂NMe₂H⁺NO₃^‐‐2)]CuONO₂ ( 9 ) and [P(C₆H₄CH₂NMe₂‐2)₃]CuCl}CuCl₂ ( 12 ) are accessible. While in 3a , 3b and 6 the phosphane 1 preferentially acts as tetrapodale ligand, in all other species only the phosphorus atom and two of the three C₆H₄CH₂NMe₂ side‐arms are datively‐bound to the appropriate copper ion. In solution a dynamic behaviour of the latter species is observed. Due to the coordination ability of X in 3a , 3b and 6 non‐coordinating anions X^‐ are present. However, in 4 one of the two perchlorate ions forms a dative oxygen‐copper bond and the second perchlorate ion acts as counter ion to {[P(C₆H₄CH₂NMe₂‐2)₃]CuOClO₃}⁺. In 7 , 9 and 10 the fragments X (X = Cl, Br, ONO₂) form a σ‐bond with the copper(I) ion. The acetate moiety in 14 acts as chelating ligand as it could be shown by IR‐spectroscopic studies. All newly synthesised cationic and neutral copper(I) and copper(II) complexes are representing stable species. Redox processes are involved in the formation of 9 and 12 by reacting 1 with 2 . The solid‐state structures of 4 , 6 , 9 and 10 are reported. In the latter complexes the copper(II) ( 4 ) or copper(I) ion ( 6 , 9 , 10 ) possesses the coordination number 4. This is achieved by the formation of a phosphorus‐ and two nitrogen‐copper‐ ( 4 , 9 , 10 ) or three ( 6 ) nitrogen‐copper dative bonds and a coordinating ( 4 ) or σ‐binding ( 9 , 10 ) ligand X. In 6 all three nitrogen and the phosphorus atoms are coordinatively bound to copper, while X acts as non‐coordinating counter‐ion. Based on this, the respective copper ion occupies a distorted tetrahedral coordination sphere. While in 4 and 10 a free, neutral Me₂NCH₂ side‐arm is present, which rapidly exchanges in solution with the coordinatively‐bound Me₂NCH₂ fragments, this unit is protonated in 10 . NO₃^‐ acts as counter ion to the CH₂NMe₂H⁺ moiety. In all structural characterized complexes 6‐membered boat‐like CuPNC₃ cycles are present.     

tert‐Butyl (6S)‐4‐hydroxy‐6‐isobutyl‐2‐oxo‐1,2,5,6‐tetra­hydropyridine‐1‐carboxyl­ate and tert‐butyl (4R,6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxopiperidine‐1‐carboxyl­ate

X‐ray studies reveal that tert‐butyl (6S)‐6‐iso­butyl‐2,4‐dioxo­piperidine‐1‐carboxyl­ate occurs in the 4‐enol form, viz. tert‐butyl (6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxo‐1,2,5,6‐tetra­hydropyri­dine‐1‐carboxyl­ate, C₁₄H₂₃NO₄, when crystals are grown from a mixture of di­chloro­methane and pentane, and has an axial orientation of the iso­butyl side chain at the 6‐position of the piperidine ring. Reduction of the keto functionality leads predominantly to the corresponding β‐hydroxy­lated δ‐lactam, tert‐butyl (4R,6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxo­piperidine‐1‐car­boxyl­ate, C₁₄H₂₅NO₄, with a cis configuration of the 4‐hydroxy and 6‐iso­butyl groups. The two compounds show similar molecular packing driven by strong O—H⋯O=C hydrogen bonds, leading to infinite chains in the crystal structure.     

(E)‐(4‐Hydroxyphenyl)(4‐nitrophenyl)diazene, (E)‐(4‐methoxyphenyl)(4‐nitrophenyl)diazene and (E)‐[4‐(6‐bromohexyloxy)phenyl](4‐cyanophenyl)diazene

Syntheses and X‐ray structural investigations have been carried out for (E)‐(4‐hydroxy­phenyl)(4‐nitro­phenyl)­diazene, C₁₂H₉N₃O₃, (Ia), (E)‐(4‐methoxy­phenyl)(4‐nitro­phenyl)­diazene, C₁₃H₁₁N₃O₃, (IIIa), and (E)‐[4‐(6‐bromo­hexyl­oxy)­phenyl](4‐cyano­phenyl)­diazene, C₁₉H₂₀BrN₃O, (IIIc). In all of these compounds, the mol­ecules are almost planar and the azo­benzene core has a trans geometry. Compound (Ia) contains four and compound (IIIc) contains two independent mol­ecules in the asymmetric unit, both in space group P (No. 2). In compound (Ia), the independent mol­ecules are almost identical, whereas in crystal (IIIc), the two independent mol­ecules differ significantly due to different conformations of the alkyl tails. In the crystals of (Ia) and (IIIa), the mol­ecules are arranged in almost planar sheets. In the crystal of (IIIc), the mol­ecules are packed with a marked separation of the azo­benzene cores and alkyl tails, which is common for the solid crystalline precursors of mesogens.     

6‐(2‐Fluorobenzylidene)‐2‐[1‐(2‐fluoro‐4‐biphenyl)ethyl]thiazolo[3,2‐b][1,2,4]triazol‐5(6H)‐one

The title compound, C₂₅H₁₇F₂N₃OS, was synthesized from 6‐(benzyl­idene)­thia­zolo­[3,2‐b][1,2,4]triazol‐5(6H)‐one. The fused thia­zolo­[3,2‐b][1,2,4]triazole system is essentially planar, and bifurcated C—H⋯O, C—H⋯N and C—H⋯F interactions are present between mol­ecules.     

4‐Amino‐3‐methyl‐6‐phenyl‐1,2,4‐triazin‐5(4H)‐one (metamitron) and 4‐amino‐6‐methyl‐3‐phenyl‐1,2,4‐triazin‐5(4H)‐one (isometamitron)

The title structures, both C₁₀H₁₀N₄O, are substitutional isomers. The N—N bond lengths are longer and the C=N bond lengths are shorter by ca 0.025 Å than the respective average values in the C=N—N=C group of asymmetric triazines; the assessed respective bond orders are 1.3 and 1.7. There are N—H⋯O and N—H⋯N hydrogen bonds in both structures, with 4‐­amino‐3‐methyl‐6‐phenyl‐1,2,4‐triazin‐5(4H)‐one containing a rare bifurcated N—H⋯N,N hydrogen bond. The structures differ in their mol­ecular stacking and the hydrogen‐bonding patterns.     

Synthesis and characterization of poly(arylene ether)s containing 6‐(4‐hydroxyphenyl)pyridazin‐3(2H)‐one or 6‐(4‐hydroxyphenyl)pyridazine moieties

A series of novel soluble pyridazinone‐ or pyridazine‐containing poly(arylene ether)s were prepared by a polycondensation reaction. The pyridazinone monomer, 6‐(4‐hydroxyphenyl)pyridazin‐3(2H)‐one ( 1 ), was synthesized from the corresponding acetophenone and glyoxylic acid in a simple one‐pot reaction. The pyridazinone monomer was successfully copolymerized with bisphenol A (BPA) or 1,2‐dihydro‐4‐(4‐hydroxyphenyl)phthalazin‐1(2H)‐one (DHPZ) and bis(4‐fluorophenyl)sulfone to form high‐molecular‐weight polymers. The copolymers had inherent viscosities of 0.5–0.9 dL/g. The glass‐transition temperatures (T_g's) of the copolymers synthesized with BPA increased with increasing content of the pyridazinone monomer. The T_g's of the copolymers synthesized from DHPZ with different pyridazinone contents were similar to those of the two homopolymers. The homopolymers showed T_g's from 202 to 291 °C by differential scanning calorimetry. The 5% weight loss temperatures in nitrogen measured by thermogravimetric analysis were in the range of 411–500 °C. 4‐(6‐Chloropyridazin‐3‐yl)phenol ( 2 ) was synthesized from 1 via a simple one‐pot reaction. 2 was copolymerized with 4,4′‐isopropylidenediphenol and bis(4‐fluorophenyl)sulfone to form high‐T_g polymers. The copolymers with less than 80 mol % pyridazinone or chloropyridazine monomers were soluble in chlorinated solvents such as chloroform. The copolymers with higher pyridazinone contents and homopolymers were not soluble in chlorinated solvents but were still soluble in dipolar aprotic solvents such as N‐methylpyrrolidinone. The soluble polymers could be cast into flexible films from solution. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3328–3335, 2006     

Highly branched and high‐molecular‐weight polyethylenes produced by 1‐[2,6‐bis(bis(4‐fluorophenyl)methyl)‐4‐MeOC6H2N]‐2‐aryliminoacenaphthylnickel(II) halides

A series of unsymmetrical 1‐[2,6‐bis(bis(4‐fluorophenyl)methyl)‐4‐MeOC₆H₂N]‐2‐aryliminoacenaphthene‐nickel(II) halides has been synthesized and fully characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance (¹H NMR), ¹³C NMR, and ¹⁹F NMR spectroscopy as well as elemental analysis. The structures of Ni1 and Ni6 have been confirmed by the single‐crystal X‐ray diffraction. On activation with cocatalysts either ethylaluminum sesquichloride or methylaluminoxane, all the title nickel complexes display high activities toward ethylene polymerization up to 16.14 × 10⁶ g polyethylene (PE) mol^?1(Ni) h^?1 at 30 °C, affording PEs with both high branches (up to 103 branches/1000 carbons) and molecular weight (1.12 × 10⁶ g mol^?1) as well as narrow molecular weight distribution. High branching content of PE can be confirmed by high temperature ¹³C NMR spectroscopy and differential scanning calorimetry. In addition, the PE exhibited remarkable property of thermoplastic elastomers (TPEs) with high tensile strength (σ_b = 21.7 MPa) and elongation at break (ε_b = 937%) as well as elastic recovery (up to 85%), indicating a better alternative to commercial TPEs. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 130–145     

The absolute configuration of (2S,4S)‐ and (2R,4R)‐2‐tert‐butyl‐4‐methyl‐3‐(4‐tolyl­sulfon­yl)‐1,3‐oxazolidine‐4‐carbaldehyde

The title enanti­omorphic compounds, C₁₆H₂₃NO₄S, have been obtained in an enanti­omerically pure form by crystallization from a diastereomeric mixture either of (2S,4S)‐ and (2R,4S)‐ or of (2R,4R)‐ and (2S,4R)‐2‐tert‐butyl‐4‐methyl‐3‐(4‐tolyl­sulfon­yl)‐1,3‐oxazolidine‐4‐carbaldehyde. These mixtures were prepared by an aziridination rearrangement process starting with (S)‐ or (R)‐2‐tert‐butyl‐5‐methyl‐4H‐1,3‐dioxine. The crystal structures indicate an envelope conformation of the oxazolidine moiety for both compounds.     

(1R,2R)‐2‐(4‐Methylenecyclohex‐2‐enyl)propyl (1R,4S)‐camphanate

Esterification of a single diastereomer of 2‐(4‐methylene­cyclohex‐2‐enyl)propanol, (II), with (1R,4S)‐(+)‐camphanic acid [(1R,4S)‐4,7,7‐trimethyl‐3‐oxo‐2‐oxabicyclo[2.2.1]heptane‐1‐carboxylic acid] leads to the crystalline title compound, C₂₀H₂₈O₄. The relative configuration of the camphanate was determined by X‐ray diffraction analysis. The outcome clarifies the relative and absolute stereochemistry of the naturally occurring bisabolane sesquiterpenes β‐turmerone and β‐sesquiphellandrene, since we have converted (II) into both natural products via a stereospecific route.     

Hexaquacobalt(II) bis(5‐hydroxy‐7‐methoxy‐4‐oxo‐2‐phenyl‐4H‐chromene‐6‐sulfonate) tetrahydrate

The title compound, [Co(H₂O)₆](C₁₆H₁₁O₇S)₂·4H₂O, with cobalt(II) at the centre of symmetry, exhibits alternating hydrophilic and hydrophobic regions. Hydrophilic regions are generated by O—H...O hydrogen bonds among sulfonate groups, involving solvent water molecules and coordinated water molecules; π–π stacking interactions assemble the flavone skeletons into columns which form the hydrophobic regions. A three‐dimensional network is built up from an extensive array of hydrogen bonds, π–π stacking interactions and electrostatic interactions between the cation and anion. As a salt of the sulfonated derivative of naturally occurring tectochrysin (5‐hydroxy‐7‐methoxyflavone), this compound offers enhanced solubility and potential biological activity over the natural product.     

Synthesis of functional phosphines with ortho‐substituted aryl groups: 2‐RC6H4PH2 and 2‐RC6H4P(SiMe3)2 (R = 2‐i‐Pr‐ or 2‐t‐Bu‐)

The synthesis and characterization of 2‐i‐PrC₆H₄PCl₂ ( 3 ), 2‐t‐BuC₆H₄PCl₂ ( 4 ), 2‐i‐PrC₆H₄PH₂ ( 5 ), 2‐t‐BuC₆H₄PH₂ ( 6 ), 2‐i‐PrC₆H₄P(SiMe₃)₂ ( 7 ), and 2‐t‐BuC₆H₄P(SiMe₃)₂ ( 8 ) are described. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:265–270, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20606     

(R)‐4‐(4‐Aminophenyl)‐2,2,4‐trimethylchroman and (S)‐4‐(4‐aminophenyl)‐2,2,4‐trimethylthiachroman

The title compounds, C₁₈H₂₁NO and C₁₈H₂₁NS, in their enantiomerically pure forms are isostructural with the enantiomerically pure 4‐(4‐hydroxyphenyl)‐2,2,4‐trimethylchroman and 4‐(2,4‐dihydroxyphenyl)‐2,2,4‐trimethylchroman analogues and form extended linear chains via N—H...O or N—H...S hydrogen bonding along the [100] direction. The absolute configuration for both compounds was determined by anomalous dispersion methods with reference to both the Flack parameter and, for the light‐atom compound, Bayesian statistics on Bijvoet differences.     

2‐Amino‐4‐chloro‐5‐formyl‐6‐[methyl(2‐methylphenyl)amino]pyrimidine and 2‐amino‐4‐chloro‐5‐formyl‐6‐[(2‐methoxyphenyl)methylamino]pyrimidine are isostructural and form hydrogen‐bonded sheets of R22(8) and R66(32) rings

2‐Amino‐4‐chloro‐5‐formyl‐6‐[methyl(2‐methylphenyl)amino]pyrimidine, C₁₃H₁₃ClN₄O, (I), and 2‐amino‐4‐chloro‐5‐formyl‐6‐[(2‐methoxyphenyl)methylamino]pyrimidine, C₁₃H₁₃ClN₄O₂, (II), are isostructural and essentially isomorphous. Although the pyrimidine rings in each compound are planar, the ring‐substituent atoms show significant displacements from this plane, and the bond distances provide evidence for polarization of the electronic structures. In each compound, a combination of N—H...N and N—H...O hydrogen bonds links the molecules into sheets built from centrosymmetric R₂²(8) and R₆⁶(32) rings. The significance of this study lies in its observation of the isostructural nature of (I) and (II), and in the comparison of their crystal and molecular structures with those of analogous compounds.     

2‐Chloro‐6‐(2‐furyl)‐9‐(4‐methoxybenzyl)‐9H‐purine

The title compound, C₁₇H₁₃ClN₄O₂, displays profound and selective activity against Mycobacterium tuberculosis. In the crystal structure, there are two independent molecules in the asymmetric unit. Intermolecular hydrogen bonding between a CH group of the purine ring and the O atom of the furan ring, and also π–π stacking in another direction, builds the three‐dimensional network.     

Molecular dynamics of 6‐methyl‐2‐phenyl‐2,3‐dihydro‐4H‐chromen‐4‐one and 6‐methyl‐2‐(4‐nitrophenyl)‐2,3‐dihydro‐4H‐chromen‐4‐one (flavanone) derivatives in a solution studied by NMR spectroscopy

Molecular dynamics of benzoxazepin, oxime, pyrazole, and thiosemicarbazone derivatives of some flavanones have been investigated in a solution using NMR. The results confirm the formation of different O–H···O, O–H···N, N···H–N type intramolecular hydrogen bonds in the pyrazole and oxime molecules. The rotational barrier energy and energy of intramolecular hydrogen bonds have been determined. Copyright © 2013 John Wiley & Sons, Ltd.     

Cobalt(II) and cobalt(III) complexes with 4′‐(4‐cyanophenyl)‐2,2′:6′,2′′‐terpyridine

4′‐Cyanophenyl‐2,2′:6′,2′′‐terpyridine (cptpy) was employed as an N,N′,N′′‐tridentate ligand to synthesize the compounds bis[4′‐(4‐cyanophenyl)‐2,2′:6′,2′′‐terpyridine]cobalt(II) bis(tetrafluoridoborate) nitromethane solvate, [Co^II(C₂₂H₁₄N₄)₂](BF₄)₂·CH₃NO₂, (I), and bis[4′‐(4‐cyanophenyl)‐2,2′:6′,2′′‐terpyridine]cobalt(III) tris(tetrafluoridoborate) nitromethane sesquisolvate, [Co^III(C₂₂H₁₄N₄)₂](BF₄)₃·1.5CH₃NO₂, (II). In both complexes, the cobalt ions occupy a distorted octahedral geometry with two cptpy ligands in a meridional configuration. A greater distortion from octahedral geometry is observed in (I), which indicates a different steric consequence of the constrained ligand bite on the Co^II and Co^III ions. The crystal structure of (I) features an interlocked sheet motif, which differs from the one‐dimensional chain packing style present in (II). The lower dimensionality in (II) can be explained by the disturbance caused by the larger number of anions and solvent molecules involved in the crystal structure of (II). All atoms in (I) are on general positions, and the F atoms of one BF₄⁻ anion are disordered. In (II), one B atom is on an inversion center, necessitating disorder of the four attached F atoms, another B atom is on a twofold axis with ordered F atoms, and the C and N atoms of one nitromethane solvent molecule are on a twofold axis, causing disorder of the methyl H atoms. This relatively uncommon study of analogous Co^II and Co^III complexes provides a better understanding of the effects of different oxidation states on coordination geometry and crystal packing.