Conditions In Excellent Yields Research Articles

Design, synthesis, molecular docking and anti-proliferative activity of novel phenothiazine containing imidazo[1,2-a]pyridine derivatives against MARK4 protein.

A series of novel phenothiazine-containing imidazo[1,2-a]pyridine derivatives were designed and synthesized under metal-free conditions in excellent yield. These derivatives were effectively transformed further into N-alkyl, sulfoxide, and sulfone derivatives. Derivatives were deployed against human microtubule affinity regulating kinase (MARK4), some molecules play crucial roles in cell-cycle progression such as G1/S transition and regulator of microtubule dynamics. Hence, molecules have shown excellent MARK4 inhibitory potential. Molecules with excellent IC50 values were selected for further studies such as ligand interactions using fluorescence quenching experiments for the binding constant. The highest binding constant was calculated as K = 0.79 × 105 and K = 0.1 × 107 for compounds 6a and 6h, respectively. Molecular docking, cell cytotoxicity, mitochondrial reactive oxygen species measurement and oxidative DNA damage were also studied to understand the mechanism of action of the molecules on cancer cells. It was found that the designed and synthesized compounds played anti-cancer roles by binding and inhibiting MARK4 protein.

Spin-Crossing in the (Z)-Selective Alkyne Semihydrogenation Mechanism Catalyzed by Mo3S4 Clusters: A Density Functional Theory Exploration.

Semihydrogenation of internal alkynes catalyzed by the air-stable imidazolyl amino [Mo3S4Cl3(ImNH2)3]+ cluster selectively affords the (Z)-alkene under soft conditions in excellent yields. Experimental results suggest a sulfur-based mechanism with the formation of a dithiolene adduct through interaction of the alkyne with the bridging sulfur atoms. However, computational studies indicate that this mechanism is unable to explain the experimental outcome: mild reaction conditions, excellent selectivity toward the (Z)-isomer, and complete deuteration of the vinylic positions in the presence of CD3OD and CH3OD. An alternative mechanism that explains the experimental results is proposed. The reaction begins with the hydrogenation of two of the Mo3(μ3-S)(μ-S)3 bridging sulfurs to yield a bis(hydrosulfide) intermediate that performs two sequential hydrogen atom transfers (HAT) from the S-H groups to the alkyne. The first HAT occurs with a spin change from singlet to triplet. After the second HAT, the singlet state is recovered. Although the dithiolene adduct is more stable than the hydrosulfide species, the large energy required for the subsequent H2 addition makes the system evolve via the second alternative pathway to selectively render the (Z)-alkene with a lower overall activation barrier.

Application of Nanomagnetic Metal-Organic Frameworks in the Green Synthesis of Nicotinonitriles via Cooperative Vinylogous Anomeric-Based Oxidation.

In the current study, we synthesized a new nanomagnetic metal-organic framework Fe3O4@MIL-53(Al)-N(CH2PO3)2 and characterized it using various techniques. This nanomagnetic metal-organic framework was used for the synthesis of a wide range of nicotinonitrile derivatives as suitable drug candidates by a four-component reaction of 3-oxo-3-phenylpropanenitrile or 3-(4-chlorophenyl)-3-oxopropanenitrile, ammonium acetate (NH4OAc), acetophenone derivatives, and various aldehydes including those bearing electron-donating, electron-withdrawing, and halogen groups, which afforded desired products (27 samples) via a cooperative vinylogous anomeric-based oxidation (CVABO) mechanism under solvent-free conditions in excellent yields (68-90%) and short reaction times (40-60 min). Increasing the surface-to-volume ratio, easy separation of the catalyst using an external magnet, and high chemical and temperature stability are the advantages of the described nanomagnetic metal-organic frameworks.

Synthesis of Alkynyl Hydrazones from Unprotected Hydrazine and Their Reactivity as Diazo Precursors.

Alkynyl hydrazones are synthesized conveniently from 2-oxo-3-butynoates and hydrazine by suppressing the susceptible formation of pyrazoles. The resultant hydrazones are transformed into alkynyl diazoacetates under metal-free and mild oxidative conditions in excellent yields. Further, the alkynyl cyclopropane and propargyl silane carboxylates are synthesized in good yields by developing an unprecedented copper-catalyzed alkynyl carbene transfer reaction.

Organocatalyzed Phospha-Michael Addition: A Highly Efficient Synthesis of Customized Bis(acyl)phosphane Oxide Photoinitiators.

Addition of the P-H bond in bis(mesitoyl)phosphine, HP(COMes)2 (BAPH), to a wide variety of activated carbon-carbon double bonds as acceptors was investigated. While this phospha-Michael addition does not proceed in the absence of an additive or catalyst, excellent results were obtained with stoichiometric basic potassium or caesium salts. Simple amine bases can be employed in catalytic amounts, and tetramethylguanidine (TMG) in particular is an outstanding catalyst that allows the preparation of bis(acyl)phosphines, R-P(COMes)2 , under very mild conditions in excellent yields after only a short time. All phosphines RP(COMes)2 can subsequently be oxidized to the corresponding bis(acyl)phosphane oxides, RPO(COMes)2 , a substance class belonging to the most potent photoinitiators for radical polymerizations known to date. Thus, a simple and highly atom economic method has been found that allows the preparation of a broad range of photoinitiators adapted to their specific field of application even on a large scale.

Synthesis, spectroscopic characterization, density functional theory study, antimicrobial and antioxidant activities of curcumin and alanine-curcumin Schiff base

In this work, a novel Schiff-base derived from curcumin and L-Alanine was synthesized under microwave conditions in excellent yield. The structural characterization has been carried out from their elemental analyses, FTIR, UV–Vis and 13C-NMR and 1H-NMR spectral techniques. The Schiff base (Cur-Ala) and curcumin (Cur) have been screened for their antimicrobial activity toward some pathogens clinically important microorganisms: Bacillus subtilis, Escherichia coli and Staphylococcus aureus, Aspergillus niger and Candida albicans. Result found that the Schiff base was more active than the curcumin. The antibacterial and antifungal activities of Cur-Ala can be attributed to its greatest dipole moment, as shown by theoretical calculations. Also, the antioxidant activity of Schiff base and curcumin were studied by DPPH, cupric ion reducing antioxidant capacity and o-phenanthroline techniques. Results indicate that Cur-Ala and Cur show more antioxidant activities than the standard antioxidants (BHT and BHA). Quantum chemical parameter calculations of Cur-Ala and Cur have been investigated by DFT using B3LYP/6-31G (d,p) basis set method to calculate the optimized structure, atomic charges, MESP, global reactivity descriptors and thermomolecular proprieties of both molecules. Communicated by Ramaswamy H. Sarma

Triazolium Salts as Lewis Acid Catalysts.

We describe a new type of nitrenium-based Lewis acids: tetraaryl-1,2,3-triazolium salts. These were fully characterized by NMR and X-ray crystallography. The Gutmann-Beckett acidity numbers were determined to be up to 35.6, which is high compared to those of previously studied nitrenium salts. These salts catalyze the facile hydrosilylation-deoxygenation of ketones, aldehydes, acetals, alcohols, ethers, and silyl ethers under mild conditions in excellent yields. To our knowledge, this represents a first example of triazolium ions used as Lewis acid catalysts.

Fabrication of self-assembled Co3O4 nano-flake for one-pot synthesis of tetrahydrobenzo[b]pyran and 1,3-benzothazole derivatives

We report the fabrication of self-assembled Co3O4 nano-flake material by dissociation of CoCl2.6H2O under basic medium using co-precipitation method. The electronic/crystalline structure and morphology and elemental purity of Co3O4 material have been analyzed by UV–Vis, fluorescence, powder X-ray diffraction, field emission scanning electron microscopy, and energy dispersive X-ray measurement. The Co3O4 nano-flake has demonstrated excellent catalytic activity in the one-pot multicomponent synthesis of tetrahydrobenzo[b]pyran and 2-aryl-1,3-benzothazole derivatives under neat conditions in excellent yields. The Co3O4 nano-flake material was recovered from the reaction mixture and reused for at least ten runs without appreciable loss of catalytic activity.

A diversity oriented clicking strategy: the stereoselective synthesis of highly-functionalised olefins from 2-substituted-alkynyl-1-sulfonyl fluorides.

A novel series of addition reactions of highly reactive 2-substituted-alkynyl-1-sulfonyl fluoride (SASF) hubs with DMSO and DMF for the synthesis of two unique sulfonyl fluoride cores is described. The stereoselective chemistry allowed the unprecedented syntheses of 12 (Z)-2-(dimethylsulfonio)-2-(fluorosulfonyl)-1-substitutedethen-1-olates and 10 (E)-1-(dimethylamino)-3-oxo-3-substitutedprop-1-ene-2-sulfonyl fluorides from DMSO and DMF, respectively. The reactions proceed expediently to give single products in excellent yield without the need for chromatographic purification. Furthermore, the utility of the DMSO derived products is demonstrated in the synthesis of synthetically valuable β-keto sulfonyl fluorides under hydrogenation conditions in excellent yields.

Green Synthesis of 1H-pyrazolo[1,2-b]phthalazinedione-2-carbonitriles in the Presence of L-proline

Background: Pyrazolophthalazinedione derivatives show various biological activities such as anti-bacterial, anti-cancer, anti-coagulant, anti-convulsant, anti-fungal, anti-hypoglycemic, anti-inflammatory, anti-tumor, anti-viral, cardiotonic, cytotoxic and vasorelaxant activities. Objective: The purpose of this study was to synthesize compounds that have various medicinal properties. Methods: Diverse 3-amino-5,10-dioxo-1-phenyl-5,10-dihydro-1H-pyrazolo[1,2-b]phthal-azine-2-- carbonitriles were synthesized from the one-pot three components green synthesis of phthalhydrazides, aromatic aldehydes and malononitrile in the presence of the proline organocatalyst in ethanol at reflux conditions in excellent yields. Results: Proline was used as an efficient organocatalyst for the one-pot three components green synthesis of diverse pyrazolophthalazinecarbonitriles. In the absence of the proline organocatalyst, the yield was very low. Also, electron withdrawing or electron releasing groups don’t have a meaningful effect on the reaction times and the structures of all products were in agreement with their IR and NMR spectra. Conclusion: In the IR spectra, the appearance of the sharp NH2 and the CN peaks at about 3300 and 2300 cm-1, respectively confirm formation of the products.

DBUH][OAc]-Catalyzed Domino Synthesis of Novel Benzimidazole Incorporated 3,5-Bis (Arylidene)-4-Piperidones as Potential Antitubercular Agents

A series of new benzimidazole incorporated 3,5-bis (arylidene)-4-piperidones were synthesized by using aryl aldehydes, piperidinone, 2-(chloromethyl)-benzimidazole and DBU acetate [DBUH][OAc] act as a catalyst under solvent free condition in excellent yields. The synthesized compounds were screened for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 4a, 4b, 4e, 4i, 4k and 4l are highly potent against both the strains. Most of the active compounds are non-cytotoxic against MCF-7, A549, HCT 116 and THP-1 cell lines. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, active site of mycobacterial enoyl-acyl carrier protein reductase (Inh A). Therefore, these compounds can be subjected for further optimization and drug development which could give promising chemical leads for treatment of TB.

Pseudo-three component reaction of indole with benzaldehyde derivatives for the preparation of bis(indolyl)methanes in the presence of nano-CuO-CeO2

In this research study, a nano-CuO-CeO2 catalyzed environmentally benign strategy for the preparation of bis(indolyl)methane derivatives via the three-component reaction between indoles and aldehyde in aqueous media under reflux conditions in excellent yields was established. The structure of the prepared compounds was confirmed using IR, 1H-NMR. The elemental analysis and morphology of the catalyst was characterized using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The results revealed that this synthetic reaction is very simple and bis(indolyl)methane derivatives produced with good yields compared to other articles. The advantages of this method include catalyst recovery, high efficiency, and easy operation method. The highest efficiency (96%) in a short time (15 min) was obtained, which is very important compared to other previous methods presented.

Synthesis of polycyclic N-heterocyclic compounds via one-pot three-component cyclization strategy.

Reported herein is an unprecedented and sequential three-component synthetic strategy for the preparation of polycyclic N-heterocyclic compounds. This synthetic protocol enabled the preparation of a series of novel nitrogen-containing pentacyclic compound under convenient conditions in excellent yields and short reaction time. The synthesized products were characterized by IR, 1H NMR, 13C NMR and mass spectra. Furthermore, the definitive structure of target compounds was confirmed by X-ray analysis.

Efficient access to pyrido[1,2-a]pyrimidines and imidazo[1,2-a]pyridines through Knoevenagel reaction/aza–ene addition/intramolecular cyclization

An expeditious metal-free heteroannulation reaction for pyrido[1,2-a]pyrimidines/imidazo[1,2-a]pyridines was developed in green solvent under mild reaction conditions by using three-component reaction of 2-chloroquinoline-3-carbaldehyde, malononitrile and nitroketen aminals, which obtained from the reaction between 1,1-bis(methylthio)-2-nitroethylene and diamines in green solvent under EtOH reflux conditions. This one-pot strategy is very simple and occurs in two steps. The present sequence is visualized as an environmentally benign process with excellent purity and high yields. An efficient, useful and general procedure for the synthesis of pyrido[1,2-a]pyrimidines/imidazo[1,2-a]pyridines via a one-pot three-component reaction of 2-chloroquinoline-3-carbaldehyde, malononitrile/ethyl 2-cyanoacetate and nitroketen aminals under mild and catalyst-free conditions in excellent yields is described. The major advantages of this protocol are high yields, mild and catalyst-free conditions, short reaction times and application of green solvent.

Sulfonic Acid-Functionalized Magnetic Nanoparticles as an Efficient Catalyst for the Synthesis of Benzo[4, 5]imidazo[1, 2-a]pyrimidine Derivatives, 2-Aminobenzothia Zolomethylnaphthols and 1-Amidoalkyl-2-naphthols.

Carbon-based sulfonated catalysts have several advantages but their separation by filtration is still a challenge. On the other hand, the synthesis of magnetic sulfonated carbon nanoparticle indicated that the magnetic separation could be an efficient way to separate the catalyst from the reaction mixture. In order to synthesize a separable magnetic Fe3O4@C-SO3H nanoparticle (MNPs) with high catalytic activity in organic transformation, three environmental-benign and low-cost sulfonic acidfunctionalized magnetic nanoparticle (Fe3O4@C-SO3H) were successfully synthesized. The Nano catalysts were prepared by solvothermal carbonization of Sucrose (Suc), Starch (Sta) or Cellulose (Cel) in the presence of Fe3O4 Nanoparticle and then grafting of the sulfonic groups on the surface of resulted Fe3O4@C nanoparticles in the presence of p-Toluenesulfonic. Then the Nano catalysts were characterized using XRD, FESEM and FT-IR. Three Fe3O4@C-SO3H were successfully synthesized. The resulted MNPs were used for the synthesis of benzo [4, 5] imidazo[1, 2-a]-pyrimidine derivatives, 2/-aminobenzothiazolomethylnaphthols and 1-amidoalkyl-2-naphthols under solvent-free conditions in excellent yields. It was found that high catalytic activity and easy magnetic separation from the reaction mixture are important achievement with regard to the efficiency and reusability of the catalyst in synthesis. The MNPs were synthesized and used as an efficient catalysts for the one-pot synthesis of benzo [4, 5] imidazo[1, 2-a]-pyrimidine derivatives, 2/-aminobenzothiazolomethylnaphthols, and 1-amidoalkyl-2- naphthols under solvent-free conditions in excellent yields. High catalytic activity and easy magnetic separation from the reaction mixture are two factors for evaluating the performance of Fe3O4@C-SO3H nanoparticles in the organic transformations.

Syntheses of spiro[indazole-3,3′-indolin]-2′-ones and spiro[indazole-3,3′-indolin]-2′-imines via 1,3-dipolar cycloadditions of arynes and studies on their isomerization reactions

A 1,3-dipolar cycloaddition reaction of arynes with 3-diazoindolin-2-ones under mild conditions in excellent yields has been developed, which allows facile access to a library of labile spiro[indazole-3,3′-indolin]-2′-ones. Spiro[indazole-3,3′-indolin]-2′-imines could be obtained as well following the same protocol. The isomerization reaction of spiro[indazole-3,3′-indolin]-2′-ones under thermal or acidic conditions has been efficiently achieved to afford a wide range of indazolo-[2,3-c]quinazolin-6(5H)-ones and the one-pot synthesis of indazolo-[2,3-c]quinazolin-6(5H)-ones from arynes and 3-diazoindolin-2-ones is also described. Whereas, spiro[indazole-3,3′-indolin]-2′-imines could not undergo the same rearrangement.

Comparison of the efficiency of two imidazole-based dicationic ionic liquids as the catalysts in the synthesis of pyran derivatives and Knoevenagel condensations

In the present work, 3,3′-(butane-1,4-diyl)bis(1-methyl-1H-imidazol-3-ium) dichloride ([C4(MIm)2]·2Cl) and 3,3′-(butane-1,4-diyl)bis(1-methyl-1H-imidazol-3-ium) hydrogen sulfate ([C4(MIm)2]·2HSO4) were prepared via adequate, solvent-free methods and characterized using FT-IR, 1H NMR, 13C NMR, and potentiometric titration techniques. These reagents were investigated in the synthesis of 5-arylidene (thio)barbituric acids, 2-arylidene malononitriles, 4H-pyrans, and pyrano[2,3-d] pyrimidineones, and their catalytic activities were compared in the promotion of these reactions. Based on the obtained results, we found that [C4(MIm)2]·2Cl showed more catalytic efficiency where a basic or weak acidic media is needed. In contrast, [C4(MIm)2]·2HSO4 is a powerful catalyst in reactions needing acidic catalysts to enhance the reaction rate. Using these reagents, the products were formed under mild and eco-friendly conditions in excellent yields during short reaction times without needing column chromatography for work-up.

Asymmetric Addition of Pyrazolones to Allenamides Catalyzed by a Chiral Phosphoric Acid

We describe a new asymmetric allylic alkylation of pyrazolones, in which an all‐carbon quaternary stereocenter with broad substrate scope and good enantioselectivity was generated. The asymmetric addition of pyrazolones to allenamides could be carried out under mild conditions in excellent yields with a relatively low catalyst loading. The allylic products with an enamide structure can be easily transformed to the pyrazolones with other functional groups, which provides a new approach for the asymmetric introduction of new functional groups into the pyrazolone skeleton.

Engineering a Nanoscale Primary Amide-Functionalized 2D Coordination Polymer as an Efficient and Recyclable Heterogeneous Catalyst for the Knoevenagel Condensation Reaction

This work reports the design, structural characterization, and catalytic behavior of the first example of primary amide-functionalized coordination polymers (CPs), namely, {[Cd2(2-bpbg)(fum)2(H2O)2]·8.5H2O}n (1) (where 2-bpbg = N,N′-bis(2-pyridylmethyl)-1,4-diaminobutane-N,N′-diacetamide and fum = fumarate). CP 1 is synthesized from a one-pot self-assembly of starting materials in methanol under ambient conditions in excellent yield and purity, allowing an easy access to multigram quantities of it within few hours. As an example, CP 1 was used as a highly efficient heterogeneous catalyst in the carbon–carbon bond-forming Knoevenagel condensation reaction for the conversion of benzaldehyde to benzylidene malononitrile. CP 1 possesses both Lewis acidic and Bronsted basic character for the presence of unsaturated metal sites and primary amide groups, respectively, making it a highly competent bifunctional catalyst for such type of reactions. Surprisingly, on the one hand, 100% conversion was observed using o...

Synthesis of 1-(benzothiazolylamino)phenylmethyl-2-naphthols accelerated by a novel magnetic nanocatalyst

4-(4-Propylpiperazine-1-yl)butane-1-sulfonic acid-modified silica-coated magnetic nanoparticles have been synthesized via covalent grafting of piperazine on (3-chloropropyl) triethoxysilane-functionalized magnetic nanoparticles through ring opening reaction of 1,4-butane sultone. The prepared reagent was characterized using different types of methods, including infrared spectroscopy (FT-IR), X-ray diffraction, thermogravimetric analysis, and scanning electron microscopy. After characterization, the catalytic activity of this reagent in the preparation of 1-(benzothiazolylamino) phenylmethyl-2-naphthols via one-pot condensation of aldehydes, 2-aminobenzothiazole, and 2-naphthol was studied in the absence of solvent. All reactions were performed under mild conditions in excellent yields during short reaction times. Using this method, the catalyst can be easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least seven times without significant degradation in its activity.