Brominated Trihalomethylenones as Versatile Precursors to 3‐Ethoxy, ‐Formyl, ‐Azidomethyl, ‐Triazolyl,and 3‐Aminomethyl Pyrazoles

5‐Bromo[5,5‐dibromo]‐1,1,1‐trihalo‐4‐methoxy‐3‐penten[hexen]‐2‐ones are explored as precursors to the synthesis of 3‐ethoxymethyl‐5‐trifluoromethyl‐1H‐pyrazoles from a cyclocondensation reaction with hydrazine monohydrate in ethanol. 3‐Ethoxymethyl‐carboxyethyl ester pyrazoles were formed as a result of a substitution reaction of bromine and chlorine by ethanol. The dibrominated precursor furnished 3‐acetal‐pyrazole that was easily hydrolyzed to formyl group. In addition, brominated precursors were used in a nucleophilic substitution reaction with sodium azide to synthesize the 3‐azidomethyl‐5‐ethoxycarbonyl‐1H‐pyrazole from the reaction with hydrazine monohydrate. These products were submitted to a cycloaddition reaction with phenyl acetylene furnishing the 3‐[4(5)‐phenyl‐1,2,3‐triazolyl]5‐ ethoxycarbonyl‐1H‐pyrazoles and to reduction conditions resulting in 3‐aminomethyl‐1H‐pyrazole‐5‐carboxyethyl ester. The products were obtained by a simple methodology and in moderate to good yields.     

A structural study of (1RS,2SR,3RS,4SR,5RS)‐2,4‐dibenzoyl‐1,3,5‐triphenylcyclohexan‐1‐ol chloroform hemisolvate and (1RS,2SR,3RS,4SR,5RS)‐2,4‐dibenzoyl‐1‐phenyl‐3,5‐bis(2‐methoxyphenyl)cyclohexan‐1‐ol

(1RS,2SR,3RS,4SR,5RS)‐2,4‐Dibenzoyl‐1,3,5‐triphenylcyclohexan‐1‐ol or (4‐hydroxy‐2,4,6‐triphenylcyclohexane‐1,3‐diyl)bis(phenylmethanone), C₃₈H₃₂O₃, (1), is formed as a by‐product in the NaOH‐catalyzed synthesis of 1,3,5‐triphenylpentane‐1,5‐dione from acetophenone and benzaldehyde. Single crystals of the chloroform hemisolvate, C₃₈H₃₂O₃·0.5CHCl₃, were grown from chloroform. The structure has triclinic (P) symmetry. One diastereomer [as a pair of (1RS,2SR,3RS,4SR,5RS)‐enantiomers] of (1) has been found in the crystal structure and confirmed by NMR studies. The dichoromethane hemisolvate has been reported previously [Zhang et al. (2007). Acta Cryst. E 63 , o4652]. (1RS,2SR,3RS,4SR,5RS)‐2,4‐Dibenzoyl‐3,5‐bis(2‐methoxyphenyl)‐1‐phenylcyclohexan‐1‐ol or [4‐hydroxy‐2,6‐bis(2‐methoxyphenyl)‐4‐phenylcyclohexane‐1,3‐diyl]bis(phenylmethanone), C₄₀H₃₆O₅, (2), is also formed as a by‐product, under the same conditions, from acetophenone and 2‐methoxybenzaldehyde. Crystals of (2) have been grown from chloroform. The structure has orthorhombic (Pca2₁) symmetry. A diastereomer of (2) possesses the same configuration as (1). In both structures, the cyclohexane ring adopts a chair conformation with all bulky groups (benzoyl, phenyl and 2‐methoxyphenyl) in equatorial positions. The molecules of (1) and (2) both display one intramolecular O—H...O hydrogen bond.     

High‐Performance,Stretchable, Wire‐Shaped Supercapacitors

A general approach toward extremely stretchable and highly conductive electrodes was developed. The method involves wrapping a continuous carbon nanotube (CNT) thin film around pre‐stretched elastic wires, from which high‐performance, stretchable wire‐shaped supercapacitors were fabricated. The supercapacitors were made by twisting two such CNT‐wrapped elastic wires, pre‐coated with poly(vinyl alcohol)/H₃PO₄ hydrogel, as the electrolyte and separator. The resultant wire‐shaped supercapacitors exhibited an extremely high elasticity of up to 350 % strain with a high device capacitance up to 30.7 F g⁻¹, which is two times that of the state‐of‐the‐art stretchable supercapacitor under only 100 % strain. The wire‐shaped structure facilitated the integration of multiple supercapacitors into a single wire device to meet specific energy and power needs for various potential applications. These supercapacitors can be repeatedly stretched from 0 to 200 % strain for hundreds of cycles with no change in performance, thus outperforming all the reported state‐of‐the‐art stretchable electronics.     

The synthesis of novel crown ethers,part X, 4‐propyl‐and 3‐ethyl‐4‐methylchromenone‐crown ethers

Starting from ethyl propionylacetate, and ethyl 2‐ethylacetoacetate we prepared 4‐propyl‐7,8‐, 4‐propyl‐6,7‐, 3‐ethyl‐4‐methyl‐7,8‐ and 3‐ethyl‐4‐methyl‐6,7‐dihydroxy‐2H‐chromenones which were allowed to react with the bis‐dihalides or ditosylates of glycols in DMF/Na₂CO₃ to afford the 6,7‐ and 7,8‐chromenone derivatives of 12‐crown‐4, 15‐crown‐4 and 18‐crown‐6. The products were identified using ir, ¹³C and ¹H nmr, ms and high resolution mass spectroscopy. The cation selectivities of chromenone crown ethers with Li⁺, Na⁺ and K⁺ cations were estimated from the steady state emission fluorescence spectra of free and cation complexed chromenone macrocyclic ethers in acetonitrile.     

Simultaneous determination of NG‐monomethyl‐l‐arginine,NG,NG‐dimethyl‐l‐arginine,NG,NG′‐dimethyl‐l‐arginine,and l‐arginine using monolithic silica disk‐packed spin columns and a monolithic silica column

We have developed and validated a high‐performance liquid chromatography method that uses monolithic silica disk‐packed spin columns and a monolithic silica column for the simultaneous determination of N^G‐monomethyl‐l ‐arginine, N^G,N^G‐dimethyl‐l ‐arginine, and N^G,N^G′‐dimethyl‐l ‐arginine in human plasma. For solid‐phase extraction, our method employs a centrifugal spin column packed with monolithic silica bonded to propyl benzenesulfonic acid as a cation exchanger. After pretreatment, the methylated arginines are converted to fluorescent derivatives with 4‐fluoro‐7‐nitro‐2,1,3‐benzoxadiazole, and then the derivatives are separated on a monolithic silica column. l ‐Arginine concentration was also determined in diluted samples. Standard calibration curves revealed that the assay was linear in the concentration range 0.2–1.0 μM for methylated arginines and 40–200 μM for l ‐arginine. Linear regression of the calibration curve yielded equations with correlation coefficients of 0.999 (r²). The sensitivity was satisfactory, with a limit of detection ranging from 3.75 to 9.0 fmol for all four compounds. The RSDs were 4.3–4.8% (intraday) and 3.0–6.8% (interday). When this method was applied to samples from six healthy donors, the detected concentrations of N^G‐monomethyl‐l ‐arginine, N^G,N^G‐dimethyl‐l ‐arginine, N^G,N^G′‐dimethyl‐l ‐arginine and l ‐arginine were 0.05 ± 0.01, 0.41 ± 0.07, 0.59 ± 0.11, and 83.8 ± 30.43 μM (n = 6), respectively.     

Synthesis of Polyfunctionalized 1,4‐Dihydropyridine‐Fused‐1,3‐Diazaheterocycles: One‐Pot Reaction of 1,1‐Bis(methylthio)‐2‐nitroethylene, 1,n‐Diamine,Arylaldehyde, and Malononitrile

An efficient, one‐pot synthetic protocol for polyfunctionalized 1,4‐dihydropyridine‐fused‐1,3‐diazaheterocycles, a class of biologically active compounds, starting from 1,1‐bis(methylthio)‐2‐nitroethylene, 1,n‐diamine, arylaldehyde, and malononitrile is described. The reactions are completed within 12–15 h under refluxing conditions and in the presence of 10 mol % of piperidine as a basic catalyst to produce the title compounds in 60–75% yields.     

A New Class of Organosuperbases,N‐Alkyl‐ and N‐Aryl‐1,3‐dialkyl‐4,5‐dimethylimidazol‐2‐ylidene Amines: Synthesis,Structure, pKBH+ Measurements,and Properties

A series of stable organosuperbases, N‐alkyl‐ and N‐aryl‐1,3‐dialkyl‐4,5‐dimethylimidazol‐2‐ylidene amines, were efficiently synthesized from N,N′‐dialkylthioureas and 3‐hydroxy‐2‐butanone and their basicities were measured in acetonitrile. The derivatives with tert‐alkyl groups on the imino nitrogen were found to be more basic than the tBu P₁ (pyrr) phosphazene base in acetonitrile. The origin of the high basicity of these compounds is discussed. In acetonitrile and in the gas phase, the basicity of the alkylimino derivatives depends on the size of the substituent at the imino group, which influences the degree of aromatization of the imidazole ring, as measured by ¹³C NMR chemical shifts or by the calculated ΔNICS(1) aromaticity parameters, as well as on solvation effects. If a wider range of imino‐substituents, including electron‐acceptor substituents, is treated in the analysis then the influence of aromatization is less predominant and the gas‐phase basicity becomes more dependent on the field‐inductive effect, polarizability, and resonance effects of the substituent.     

Mass spectrometric studies of cis‐ and trans‐1a,3‐disubstituted‐1,1‐dichloro‐4‐formyl‐1a, 2,3,4‐tetrahydro‐lH‐azirino[1,2‐a]1,5]benzodiazepines

The mass spectrometric behaviour of four cis‐ and trans‐1a,3‐disubstituted‐1,1‐dichloro‐4‐formyl‐1a,2,3,4‐tetrahydro‐1H‐azirino [1, 2‐a][1,5]benzodiazepines has been studied with the aid of mass‐analysed ion kinetic energy spectrometry and exact mass measurements under electron impact ionization. All compounds show a tendency to eliminate a chlorine atom from the aziridine ring, and then eliminate a neutral propene or styrene from the diazepine ring to yield azirino [1,2‐b][1,3] benzimidazole ions. These azirino [1,2‐a][1,5]‐benzodiazepimes can also eliminate HCl, or Cl plus HCl simultaneously to undergo a ring enlargement rearrangement to yield 1,6‐benzodiazocine ions, which further lose small molecular fragments, propyne or phenylacetylene, with rearrangement to give quinoxaline ions.     

Star‐like polyfluorenes based on 2,4,6,8, 10,12‐hexabenzyl‐2,4,6,8,10,12‐hexaazaisowurtzitane caged‐core: toward non‐aggregating,blue‐light‐emitting polymers

Multi‐functionality compound 2,4,6,8,10,12‐hexa(p‐bromo)‐benzyl‐2,4,6,8,10,12‐hexaazaiso‐wurtzitane (Br‐HBIW) was synthesized and used for the core of star‐like polymers. Star‐like polyfluorene based on 2,4,6,8,10,12‐hexabenzyl‐2,4,6,8,10,12‐hexaazaisowurtzitane (HBIW) caged‐core was synthesized by Suzuki coupling method. The comparative studies between the star‐like polyfluorene and the linear polyfluorene based on UV–Vis and photoluminescence (PL) spectra revealed that the bulky HBIW cage could reduce the chain aggregation and π–π interaction, so brought about improved PL quantum efficiency and annealing PL stability. Such results could be owed to the successful suppression of excimers formation, which originated from the incorporation of the HBIW cage and star‐like architecture. Copyright © 2009 John Wiley & Sons, Ltd.     

High‐Performance,Stretchable, Wire‐Shaped Supercapacitors

A general approach toward extremely stretchable and highly conductive electrodes was developed. The method involves wrapping a continuous carbon nanotube (CNT) thin film around pre‐stretched elastic wires, from which high‐performance, stretchable wire‐shaped supercapacitors were fabricated. The supercapacitors were made by twisting two such CNT‐wrapped elastic wires, pre‐coated with poly(vinyl alcohol)/H₃PO₄ hydrogel, as the electrolyte and separator. The resultant wire‐shaped supercapacitors exhibited an extremely high elasticity of up to 350 % strain with a high device capacitance up to 30.7 F g^?1, which is two times that of the state‐of‐the‐art stretchable supercapacitor under only 100 % strain. The wire‐shaped structure facilitated the integration of multiple supercapacitors into a single wire device to meet specific energy and power needs for various potential applications. These supercapacitors can be repeatedly stretched from 0 to 200 % strain for hundreds of cycles with no change in performance, thus outperforming all the reported state‐of‐the‐art stretchable electronics.     

Microwave‐assisted extraction and high‐throughput monolithic‐polymer‐based micro‐solid‐phase extraction of organophosphorus,triazole, and organochlorine residues in apple

A high‐throughput micro‐solid‐phase extraction device based on a 96‐well plate was constructed and applied to the determination of pesticide residues in various apple samples. Butyl methacrylate and ethylene glycol dimethacrylate were copolymerized as a monolithic polymer and placed in the cylindrically shaped stainless‐steel meshes of 96‐micro‐solid‐phase extraction device and used as an extracting unit. Before the micro‐solid‐phase extraction, microwave‐assisted extraction was employed to facilitate the transfer of the pesticide residues from the apple matrix to liquid media. Then, 1 mL of the aquatic samples was transferred into the 96‐well plate and the 96‐micro‐solid‐phase extraction device was applied for the extraction of the selected pesticides. Influential parameters, such as sorbent‐to‐sorbent reproducibility, microwave‐assisted extraction time, ionic strength and micro‐solid‐phase extraction time, were optimized. The limits of quantitation were below 120 μg/kg, which are lower than the maximum residue limits. The developed method was successfully implemented for the extraction and determination of the selected pesticides from 20 different apple samples gathered from local markets. Phosalone was identified and quantified at the concentration level of 147 (±16.4) μg/kg in one of the samples.     

The First One‐Pot,Solvent‐Free,Microwave‐Accelerated,Three‐Component Synthesis of Spirothiazolidin‐4‐ones via Staudinger/Aza‐Wittig Coupling/Cyclization

An efficient and rapid, solvent‐free, microwave‐accelerated, one‐pot, three‐component protocol for the synthesis of spirothiazolidin‐4‐ones from organic azides is reported for the first time via Staudinger/aza‐Wittig coupling/cyclization. The solvent‐free approach overcomes the limitations associated with the prevailing solution‐phase methodologies in the case of amines. In particular, its novelty is that it eradicates the vital limitation, i.e., the accumulation of H₂O (by‐product), which is known to affect the yield and rate of the reaction, thus affording the spirothiazolidin‐4‐ones in short reaction times in excellent yields.     

Silver Salt and Derivatives of 5‐Azido‐1H‐1, 2, 4‐triazole‐3‐­carbonitrile

This study features the preparation of three new energetic C‐azido‐1, 2, 4‐triazoles, with the anion of one being a new binary C–N compound. 5‐Azido‐1H‐1, 2, 4‐triazole‐3‐carbonitrile ( 1 ) was prepared from 5‐amino‐1H‐1, 2, 4‐triazole‐3‐carbonitrile and further derivatized to 5‐azido‐1H‐1, 2, 4‐triazole‐3‐carbohydroximoyl chloride ( 5 ) with 3‐azido‐1H‐1, 2, 4‐triazole‐5‐carboxamidoxime ( 3 ) as an intermediate. The ability of 1 and 3 for salt formation was shown with the respective silver salts 2 and 4 . All compounds were well characterized by various means, including IR and multinuclear NMR spectroscopy, mass spectrometry, and DSC. The molecular structures of 1 , 3 , and 5 in the solid state were determined by single‐crystal X‐ray diffraction. The sensitivities towards various outer stimuli (impact, friction, electrostatic discharge) were determined according to BAM standards. The silver salts were additionally tested for their potential as primary explosives.     

Water‐Soluble Flavonol (=3‐Hydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐one) Derivatives: Chemical Synthesis,Colouring, and Antioxidant Properties

Water‐soluble derivatives of rutin, a very common glycoside of quercetin (=3,3′,4′,5,7‐pentahydroxyflavone=2‐(3,4‐dihydroxyphenyl)‐3,5,7‐trihydroxy‐4H‐1‐benzopyran‐4‐one) and a potent plant antioxidant from the flavonol family, were synthesized by simple chemical procedures aimed at introducing carboxy or sulfo groups at the sugar moiety (Scheme 1). Such derivatives form stable molecular complexes with malvin, a polyphenolic pigment from the anthocyanin family, and thereby prove to be very effective in the enhancement (hyperchromism) and variation (bathochromism) of natural colours. The H₂O‐solubilizing carboxylate and sulfate groups are shown to deeply modify the enthalpy‐entropy balance of the pigment‐flavonol complexation (copigmentation). A molecular interpretation of the complexation‐induced bathochromic shift in the pigment VIS band is proposed. Finally, the H₂O‐soluble rutin derivatives are shown to retain the high antioxidant ability of rutin as evidenced by their efficient trapping of the coloured radical DPPH (=2,2‐diphenyl‐1‐(2,4,6‐trinitrophenyl)hydrazyl).     

Synthesis,characterization & in vitro antimicrobial‐antioxidant studies of novel N,1‐diphenyl‐4,5‐dihydro‐1H‐1,2,4‐triazol‐3‐amine derivatives

A new series of 1,2,4‐triazole was designed, synthesized, and characterized as remarkable antimicrobial and antioxidant agents. These heterocycles have been prepared from the cyclization reactions of Schiff bases 3 ( a‐k ) with phenylhydrazine by refluxing under the alkaline medium. The Schiff bases in turn were realized in good yields from the condensation reactions of N‐phenylurea with different aromatic aldehydes. The structures of the intermediates 3 ( a‐k ) and final heterocycles 4 ( a‐k ) have been fully characterized through their spectral parameters.     

Biocompatible and pH‐responsive triblock copolymer mPEG‐b‐PCL‐b‐PDMAEMA: Synthesis,self‐assembly,and application

A series of well‐defined amphiphilic triblock copolymers [polyethylene glycol monomethyl ether]‐block‐poly(ε‐caprolactone)‐block‐poly[2‐(dimethylamino)ethyl methacrylate] (mPEG‐b‐PCL‐b‐PDMAEMA or abbreviated as mPEG‐b‐PCL‐b‐PDMA) were prepared by a combination of ring‐opening polymerization and atom transfer radical polymerization. The chemical structures and compositions of these copolymers have been characterized by Fourier transform infrared spectroscopy, ¹H NMR, and thermogravimetric analysis. The molecular weights of the triblock copolymers were obtained by calculating from ¹H NMR spectra and gel permeation chromatography measurements. Subsequently, the self‐assembly behavior of these copolymers was investigated by fluorescence probe method and transmission electron microscopy, which indicated that these amphiphilic triblock copolymers possess distinct pH‐dependent critical aggregation concentrations and can self‐assemble into micelles or vesicles in PBS buffer solution, depending on the length of PDMA in the copolymer. Agarose gel retardation assays demonstrated that these cationic nanoparticles can effectively condense plasmid DNA. Cell toxicity tests indicated that these triblock copolymers displayed lower cytotoxicity than that of branched polyethylenimine with molecular weight of 25 kDa. In addition, in vitro release of Naproxen from these nanoparticles in pH buffer solutions was conducted, demonstrating that higher PCL content would result in the higher drug loading content and lower release rate. These biodegradable and biocompatible cationic copolymers have potential applications in drug and gene delivery. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1079–1091, 2010     

(2S,3S)‐2,6‐Dimethylheptane‐1,3‐diol,the oxygenated side chain of 22(S)‐hydroxycholestrol,and its synthetic precursor (R)‐4‐benzyl‐3‐[(2R,3S)‐3‐hydroxy‐2,6‐dimethylheptanoyl]‐1,3‐oxazolidin‐2‐one

(2S,3S)‐2,6‐Dimethylheptane‐1,3‐diol, C₉H₂₀O₂, (I), was synthesized from the ketone (R)‐4‐benzyl‐3‐[(2R,3S)‐3‐hydroxy‐2,6‐dimethylheptanoyl]‐1,3‐oxazolidin‐2‐one, C₁₉H₂₇NO₄, (II), containing C atoms of known chirality. In both structures, strong hydrogen bonds between the hydroxy groups form tape motifs. The contribution from weaker C—H...O hydrogen bonds is much more evident in the structure of (II), which furthermore contains an example of a direct short Osp³...Csp² contact that represents a usually unrecognized type of intermolecular interaction.     

Diastereospecific synthesis of (S,S)‐2‐substituted‐4,4‐diphenyl‐3, 1‐oxazabicyclo[3.3.0]octanes

(S,S)‐2‐Substituted‐4,4‐diphenyl‐3,1‐oxazabicyclo[3.3.0]octanes were synthesized diaster‐eospecifically from aldehydes and (S)‐2‐(hydroxydiphenylmethyl)pyrrolidine, which was obtained from L ‐proline, under acid‐catalyzed conditions in anhydrous toluene. The stereospecificity of the condensation reaction is discussed. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:42–45, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10064     

Functionalization of Quinazolin‐4‐ones Part 3: Synthesis,Structures Elucidation,DNA‐PK,PI3K,and Cytotoxicity of Novel 8‐Aryl‐2‐morpholino‐quinazolin‐4‐ones

A series of novel 8‐aryl‐2‐morpholino quinazolines ( 11a – n , 12a – d , 14a – f , and 15 ) were synthesized from the precursor 2‐thioxo quinazolin‐4‐ones 8 . The 8‐aryl‐2‐morpholino quinazolines compounds were assayed for DNA‐PK and PI3K. All compounds showed low DNA‐PK % inhibition activity at 10 μM compound concertation, and the most active was 8‐(dibenzo[b,d]thiophen‐4‐yl) 12d with 38% inhibition. Similar pattern of PI3K α, β, γ, and δ isoforms inhibition activity at 10 μM were observed. The most active isoform was PI3K δ of 41% inhibition for 8‐(dibenzo[b,d]furan‐4‐yl) compound 11 . Most compounds were less active than expected in spite of the strong structural resemblance to known inhibitors ( NU7441 , 3 , 4 , and 6 ). Loss of activity could be attributed to the tautomerization to the aromatic enol (4‐OH), which could specify that the important functional group for the activity is the 4‐carbonyl (C=O) group. Alternatively, the aromatization of the pyrimidine heterocyclic ring could alter the conformation, and thus binding site, of the 2‐morpholine ring, which could reduce the compound‐receptor hydrogen bonding to the morpholine 4‐oxygen. Selected compounds displayed appreciable cytotoxicity with 6‐chloro‐8‐(dibenzo[b,d]thiophen‐4‐yl)‐2‐morpholinoquinazolin‐4(1H)‐one 11j exhibiting the greatest activity with an IC₅₀ of 9.95 μM. Therefore, the mechanism of the cytotoxicity of compound 11j were not through DNA‐PK or PI3K inhibition activity.     

Design,Synthesis, Characterization,and Antimicrobial Evaluation of Novel 2‐(3, 5‐di methoxy‐4‐((1‐aryl‐1H‐1, 2, 3‐triazole‐4‐yl) methoxy) phenyl) benzo[d]thiazoles

A series of 12 new 2‐(3, 5‐dimethoxy‐4‐((1‐Aryl‐4H‐1, 2, 3‐triazol‐4‐yl) methoxy) phenyl) benzo[d]thiazoles have been synthesized from the reaction of 4‐hydroxy‐3, 5‐dimethoxybenzaldehyde, o‐amino thiophenol, propargyl bromide, and different substituted aromatic azides using “click chemistry”. The structures of these compounds were established on the basis of Fourier Transform infrared, ¹H NMR, ¹³C–NMR, and mass spectral analysis. Compounds ( 6a–l ) were screened for in vitro antimicrobial activity.