One-pot Three-component Synthesis Research Articles

A Hollowed-Out Heterometallic Cluster for Catalytic Knoevenagel Condensation.

Lanthanide-containing clusters are synthetically Lanthanide-containing clusters are synthetically challenging and with significant chemical and materials applications.Herein, two isostructural heterometallic clusters of the formula (NO3)12@[Ln132Ni78(OH)292(IDA)48(CH3COO)96(NO3)12(H2O)78]Cl44·xH2O·yCH3OH(IDA = iminodiacetate; Ln = Gd1,x= 110,y= 0; Ln = Eu2,x= 95,y= 40)were obtained via co-hydrolysis of Ln3+(Gd3+orEu3+) and Ni2+in the presence of iminodiacetate(IDA). Crystallographic studies show that each features a truncated tetrahedral core of Ln132Ni78within which avoid of 5.5 Å in diameter; connecting the central cage and its exterior are four trumpet-like passageways surface-decorated with dinuclear units of [Gd(μ3-OH)2Gd]. Mass spectroscopic analyses indicate that both clusters maintained their structural integrity in aqueous solution, with cryo-electron microscopyproviding the most convincing visual evidence in support of the cluster's solution stability. Size-selective Knoevenagel condensation, believed to occur in the passageways on the basis of experimental and molecular modeling results,was achieved in the presence of1. The application of 1as a uniquely structured molecular reactor and a recyclable heterogeneous catalyst was further illustrated by the one-pot three-component synthesis of biologically and pharmaceutically significant4H-pyran derivatives.

Synthesis, Antimicrobial and Antioxidant Activity of Some New Pyrazolines Containing Azo Linkages.

Pyrazolines and azo-pyrazolines are influential groups of heterocyclic compounds with two nitrogen atoms inside the five-membered ring. They play an important role in a wide range of biological processes, such as antifungal, antioxidant, antimalarial and other antimicrobial activities. The main objective of this study is to synthesize some new heterocyclic compounds with antioxidant and antimicrobial activity Methods: One-pot three components and traditional synthesis of new azo-pyrazoline compounds were achieved in this work. The preparation process has been started by diazotizing 4-(6-methylbenzothiazol-2-yl) benzamine and its coupling reaction with 4-hydroxy acetophenone producing azo-acetophenone, followed by benzylation with benzyl chloride to form the starting material, azo-benzyloxy acetophenone. A series of substituted benzaldehydes were reacted with the latter compound via one pot and classical methods, forming new chalcones containing azo linkages and benzyloxy moieties, which were then converted into new target azo-pyrazoline derivatives. The structures of the synthesized compounds were confirmed by spectroscopic techniques using FT-IR, 1H-NMR, 13C-NMR, and 13C- DEPT- 135 spectra. Finally, the synthesized compounds were screened for their antioxidant and antimicrobial activities against Staphylococcus aureus and Escherichia coli. Overall, the one-pot three-component synthesis of pyrazoline compounds generally provides advantages in terms of efficiency, simplicity, and time-consumption compared to classical synthesis methods. Hence, the study advocates the one-pot method because it eliminates the tedious process of making chalcones, which takes time, materials, and unnecessary effort. Therefore, this is the most convenient and effective approach to green chemistry.

Catalyst-free one-pot three-component synthesis and in silico bioactivity of new 4-pyrazolyl pyrano[3,4-c] pyrrole derivatives

Catalyst-free one-pot three-component synthesis and in silico bioactivity of new 4-pyrazolyl pyrano[3,4-c] pyrrole derivatives

Magnetic BiFeO3 nanoparticles: a robust and efficient nanocatalyst for the green one-pot three-component synthesis of highly substituted 3,4-dihydropyrimidine-2(1H)-one/thione derivatives.

In this research, magnetic bismuth ferrite nanoparticles (BFO MNPs) were prepared through a convenient method and characterized. The structure and morphological characteristics of the prepared nanomaterial were confirmed through analyses using Fourier-transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), elemental mapping, powder X-ray diffraction (XRD), N2 adsorption-desorption isotherms and vibrating sample magnetometry (VSM) techniques. The obtained magnetic BFO nanomaterial was investigated, as a heterogeneous Lewis acid, in three component synthesis of 3,4-dihydropyrimidin-2 (1H)-ones/thiones (DHPMs/DHPMTs). It was found that the BFO MNPs exhibit remarkable efficacy in the synthesis of various DHPMs as well as their thione analogues. It is noteworthy that this research features low catalyst loading, good to excellent yields, environmentally friendly conditions, short reaction time, simple and straightforward work-up, and the reusability of the catalyst, distinguishing it from other recently reported protocols. Additionally, the structure of the DHPMs/DHPMTs was confirmed through 1H NMR, FTIR, and melting point analyses. This environmentally-benign methodology demonstrates the potential of the catalyst for more sustainable and efficient practices in green chemistry.

One-pot Three-component Synthesis of Fully and Diversely Functionalized Pyrans and Spiropyrans Using Sodium Formate as Catalyst in Aqueous Ethanol at Room Temperature

Abstract: A convenient and general method has been developed for the synthesis of fully and diversely functionalized pyrans via one-pot three-component reactions of various aryl or heteroaryl aldehydes, malononitrile, and 1,3-dimethyl/1,3-diethyl-acetonedicarboxylates in the presence of a catalytic amount of sodium formate as an efficient organocatalyst in aqueous ethanol at room temperature. All the scaffolds were synthesized in excellent yields within 2.5 hours. Under the same reaction conditions, fully and diversely functionalized spiro-pyrans were also synthesized in excellent yields from the reaction of isatin, malononitrile, and 1,3-dimethyl/1,3-diethylacetonedicarboxylates. All the products were isolated pure just by simple filtration. Synthesis of fully and diversely functionalized biologically promising pyrans, excellent yields, use of organocatalyst, less toxic solvent, no column chromatographic purification, and energy efficiency are some of the major advantages of this newly developed protocol. method: In a clean test tube a magnetic stir bar, 0.5 mmol of aldehydes (1a-1i), 0.5 mmol of malononitrile (2; 0.033 g) and 0.5 mmol of 1,3-dimethylacetonedicarboxylate (3a; 0.087 g) or 1,3-diethylacetonedicarboxylate (3b; 0.101 g), 4 ml aqueous ethanol (1:1 v/v) and 20 mol% sodium formate were taken sequentially. The whole reaction mixture was stirred at room temperature for the time mentioned in Table 2. The progress of reaction was monitored by TLC. By using the same amount of catalyst and solvent the synthesis of methyl/ethyl-2'-amino-3'-cyano-6'-(2-meth/ethoxy-2-oxoethyl)-2-oxospiro[indoline-3,4'-pyran]-5'-carboxylate (6a/6b) was achieved from the reactions of 0.5 mmol of isatin (5; 0.0735 g), 0.5 mmol of malononitrile (2; 0.033 g) and 0.5 mmol of 1,3-dimethylacetonedicarboxylate (3a; 0.0871 g) or 1,3-diethylacetonedicarboxylate (3b; 0.1011 g). After the completion of each reaction, the desired products were isolated simply by filtration and subsiquent washing with aqueous ethanol (EtOH:H2O = 1:1).

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation.

A one-pot three-component synthesis of substituted meta-hetarylanilines from heterocycle-substituted 1,3-diketones has been developed. The electron-withdrawing power of the heterocyclic substituent (which can be estimated on the basis of calculated Hammett constants) in the 1,3-diketone plays a pivotal role in the studied reaction. The series of meta-hetarylanilines prepared (21-85% isolated yield) demonstrates the synthetic utility of the developed method.

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization.

A one-pot three-component Biginelli synthesis of dihydropyrimidinones/thiones/selenones via acetic acid or solvent-free Yb(OTf)3-catalyzed tandem reaction of β-ketosulfone (dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide), an appropriate urea, and arylaldehyde has been developed. The reaction proceeds with high chemo- and regioselectivity to give diverse DHPMs in reasonable yields up to 95%. Moreover, an SO2-containing analogue of anticancer drug-candidate enastron (SO2 vs C=O) was obtained by using the here reported method in gram scale. We also demonstrate the reactivity of the Biginelli product in various directions - synthesis of condensed thiazoles and tetrazoles. In silico assessment of ADMET parameters shows that most compounds meet the lead-likeness requirements. The biological profiles of new compounds demonstrate high probability levels of activity against the following pathogens/diseases: Candida albicans, Alphis gossypii, Tripomastigote Chagas, Tcruzi amastigota, Tcruzi epimastigota, Leishmania amazonensis, and Dengue larvicida.

One-pot three-component synthesis of 2,4-dimethoxy-5,8,9,10-tetrahydropyrimido[4,5-b]quinolinone derivatives along with in silico and in vitro investigation of their antimalarial activity

Pyrimidoquinolinone-derived compounds have exhibited a broad spectrum of biological activities and have been acknowledged as a potential antimalarial scaffold through multiple conventional strategies. In the present study, a novel series of 2,4-dimethoxy-5,8,9,10-tetrahydropyrimido[4,5-b]quinolinones 4(a-m) were synthesized via a one-pot three-component reaction of cyclohexane-1,3‑dione, 4-amino-2,6-dimethoxypyrimidine and various aldehyde with l-proline as the catalyst and acetic acid as the solvent under reflux condition. In vitro antimalarial activity toward P. falciparum 3D7 strain cultures were investigated. Compounds 4b and 4m demonstrated significant efficacy against strains of P. falciparum, with IC50 values of 0.63 and 0.65 μg/mL, respectively. The results were also supported by molecular docking and ADME assays.

Eco-Friendly One-Pot Synthesis of Tetrahydrobenzo[b]Pyran and Dihydropyrano[3,2-c]Chromene Derivatives Using Functionalized Fe3O4@SiO2@SO3H Under MWI

The present work describes a greener method of preparation of Fe3O4 nanoparticles, which are then functionalized to Fe3O4@SiO2@SO3H, and employed in the one-pot three-component synthesis of tetrahydrobenzo[b]pyran and dihydropyrano[3,2-c]chromene derivatives. These synthesized derivatives are an important class of heterocyclic scaffolds and exhibit significant potential as anti-coagulant, diuretic, spasmolytic, anticancer, and anti-anaphylactic agents. The prepared MNP-based catalysts were characterized using XRD, FE-SEM, VSM, TG-DTA, and Raman spectroscopy. The synthesis of derivatives involved the condensation reaction of enolizable compounds with aldehyde, dimedone, and ethyl cyanoacetate for tetrahydrobenzo[b]pyran, and the reaction of aromatic aldehyde, 4-hydroxycoumarin, and malononitrile for dihydropyrano[3,2-c]chromene synthesis. The reaction was optimized using different techniques such as stirring, ultrasonication, and microwave irradiation, with microwave irradiation method demonstrating faster product separation and high yield. The homogeneity of the isolated product was analyzed by FT-IR,1H-13C-NMR, and mass spectrometry. The advantages of this method include its simplicity, eco-friendliness, cost-effectiveness, and it also evades the use of toxic metals and solvents. The product is easily isolated through a simple workup process and recrystallization using ethanol yields pure product isolation.

Easy functionalization of carbon nano-onions with disulfides and their use as recyclable heterogeneous organocatalysts

A facile functionalization of carbon nano-onions (CNO), through an atom economical one-step process, with a series of different generation (2.0, 2.5, and 3.0G) poly(amidoamine) (PAMAM) dendrimers with a cystamine core and endowed with either methyl ester or amino groups in the periphery has been reported. The radical addition reaction onto CNO surface, after the homolytic rupture of the S–S bond of cystamine, afforded CNO-PAMAM hybrids, which were extensively characterized using various analytical and spectroscopic techniques such as thermogravimetric analysis (TGA), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, solid state 13C NMR, Raman, X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS) and zeta potential (ZP). Morphological and textural properties were also investigated by high-resolution transmission electron microscopy (HRTEM) analysis and N2 adsorption/desorption isotherms. Furthermore, the presence and availability of –NH2 groups has been demonstrated by applying the functionalized CNO with PAMAM 2.0G and 3.0G as heterogeneous and recyclable organocatalysts in the one-pot three-component synthesis of 2-amino-4H-chromene derivatives.

Synthesis, Characterization, and Optimization of Novel Furan-ring Fused Chalcones via Radical Cyclization of α,β-Unsaturated Ketones and Cyclic Ketone

Abstract: Novel Furan-ring Fused Chalcones (FFC) were synthesized using a radical cyclization reaction of α,β-unsaturated ketones with cyclic ketone as the model reaction to attain this goal. In this study, traditional and microwave-assisted methods for the efficient and cost-effective synthesis of furan-ring fused chalcones in mild reaction conditions are compared and optimized. The goal is to develop a reliable and adaptable synthetic technique that may be used to produce these useful chalcone derivatives quickly and effectively. The optimal experimental conditions for these reactions were carefully determined using two independent methodologies: conventional (Method A) and microwave (Method B). The results indicated that the proposed method B could be used effectively in the future to synthesize novel furans with short reaction times and acceptable yields (87-94 %), and products were purified by column chromatography and preparative thin layer chromatography (PTLC). All new compounds were characterized by 1H-NMR, 13C-NMR, LC-MS, and elemental analyses.

Design and one-pot synthesis of new substituted pyrrolo[1,2-a]thieno[3,2-e]pyrimidine as potential antitumor agents: in vitro and in vivo studies

A new efficient and versatile one-pot three-component synthesis of substituted pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives has been developed. It is based on a multistep cascade reaction from 2-aminothiophenes and 2-hydroxy-4-oxobut-2-enoic acids, and derivatives of cyanoacetic acid catalyzed by diisopropylethylamine. As a result, novel pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives (21 compounds) were synthesized in a mild reaction conditions with a high yield. The structures of the developed compounds were confirmed by NMR and elemental analysis. The influence of electron-withdrawing or electron-donor substituents on the antitumor activity of the developed compounds has been identified. In vitro screening analysis of 21 compounds revealed six lead candidates (12aa, 12dc, 12hc, 12ic, 12lb, and 12mb) that demonstrated the most significant antitumor activity against B16-F10, 4T1 and CT26 cells. Necrosis/apoptosis assay showed that apoptosis was the predominant mechanism of cell death. Molecular docking analysis revealed several potential targets for tested compounds, i.e. phosphatidylinositol 5-phosphate 4-kinase (PI5P4K2C), proto-oncogene serine/threonine-protein kinase (Pim-1), nicotinamide phosphoribosyltransferase (NAMPT) and dihydrofolate reductase (DHFR). The lead compound (12aa) can effectively induce cell apoptosis, possesses a high yield (98 %) and requires low-cost starting chemicals for its synthesis. In vivo experiments with melanoma-bearing mice confirmed that 12aa compound resulted in the significant tumor inhibition on 15 d after the therapy. In particular, tumor volume was ∼0.19 cm3 for 50 mg/kg versus ∼2.39 cm3 in case of untreated mice and tumor weight was ∼71.6 mg for 50 mg/kg versus ∼452.4 mg when considered untreated mice. Thus, our results demonstrated the high potential of the 12aa compound in the treatment of melanoma and can be recommended for further preclinical studies.

Efficient synthesis of dihydropyranochromene derivatives via nanocopper immobilized on Zn/Cr-LDH functionalized with poly(p-phenylenediamine)

A new catalyst, poly(p-phenylenediamine) functionalized with copper nanoparticles stabilized on layered double hydroxide (LDH@poly(p-phenylenediamine)@CuI), was prepared. The structure of the new catalyst was identified and confirmed using different analyzes such as FESEM, EDX, XRD, TGA and elemental mapping. The efficiency of the mentioned catalyst was confirmed in the three-component one-pot synthesis of various derivatives of dihydropyrano[3,2-c]chromene in aqueous ethanol solvent. The structure of the synthesized products was confirmed using infrared spectrometry (FT-IR), nuclear magnetic resonance (1H NMR and 13C NMR) and Mass techniques. High yield of products, short reaction time, easy purification, reuse of catalyst, and the use of a soft reaction method can be considered as the main advantages of this method. Additionally, this catalyst was recycled four times without a significant loss of catalytic power.

A simple, highly efficient, guanidine•HCl catalysed one-pot three-component synthesis of spiro chromeno-pyrimidin- and novel spiro pyrano-pyrimidin-indolinone derivatives and their anticancer activity against Burkitt's lymphoma CA-46 cell lines

A novel, efficient and guanidine•HCl catalysed synthesis of some important uracil and thiouracil-based spiro chromeno- and novel spiro pyrano-indolinones from cyclohexane/cyclopentane-1,3-diketones, malonyl ureas/thiourea and isatins/acenapthenequinone in water under thermal condition is reported. The products are obtained in excellent yield within 40 min. Out of 36 test compounds, 21 were found to be very good inhibitors of Burkitt's Lymphoma CA-46 cell lines; and 2 of them are very powerful inhibitors. The 8 highly potent compounds which inhibited CA-46 cell lines did not show any activity towards MCF-7 and HeLa cell lines.

Ferric oxide nanocatalyst: synthesis, characterization, and application in the one-pot three-component synthesis of 3,4,5-trisubstituted isoxazole derivatives

Ferric oxide nanocatalyst: synthesis, characterization, and application in the one-pot three-component synthesis of 3,4,5-trisubstituted isoxazole derivatives

An efficient three-component one-pot synthesis of 3, 4-dihydropyrimidin-2-(1H)-thione derivatives with a mesoporous iron ion exchanged Indian clay catalyst

An efficient three-component one-pot synthesis of 3, 4-dihydropyrimidin-2-(1H)-thione derivatives with a mesoporous iron ion exchanged Indian clay catalyst

Catalytic One-pot Solvent Free Synthesis, Biological Activity, and Docking Study of New Series of 1, 3-thiazolidine-4-one Derivatives Derived from 2- (P-tolyl) Benzoxazol-5-amine.

In this study, a simple triethylammonium salt of phosphoric acid (triethylammonium dihydrogen phosphate) (4) in the liquid state was utilized as an inexpensive, efficient one-pot three components, solvent-free synthesis of thiazolidine-4-one derivatives, with good to excellent yields. Techniques such as FT-IR, 1H-NMR, 13C-NMR, 13C-NMR-DEPT-135, and MS. were used for the structural elucidation. The high biotic efficiency of the newly obtained compounds was confirmed by in vitro antimicrobial action against Gram-positive (S. Aureus), Gram-negative bacteria (P. Aeruginosa and E. Coli) and antifungal activity (C. Albicans) via microplate titer dilution technique. Finally, a molecular docking study was performed with a resolved crystal structure of S. Aureus D-alanine alanyl carrier protein ligase (PDB ID: 7VHV). This investigation aimed to synthesize a new series of thiazolidine-4-one derivatives combined with benzoxazole moiety. Ionic liquid assistance one-pot solvent-free synthesis method used to synthesize a new series of thiazolidine-4-one derivative 10(a-e). Structural identification of new synthesis and biological evaluation via techniques of (IR, 1H-NMR, 13C-NMR, 13C-NMR-DEPT-135, and MS). Ionic liquid is utilized as an inexpensive, efficient one-pot three-component solvent-free synthesis of thiazolidine-4-one derivatives with good to excellent yields. Most of the synthesized compounds showed high biological and anti-fungal activity, in line with the docking study against mentioned microorganism and crystal structure of PDB (ID: 7VHV), respectively.

Copper Immobilized on Modified LDHs as a Novel Efficient Catalytic System for Three-Component Synthesis of Pyrano[2,3-d]pyrimidine and pyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidine Derivatives.

A novel catalyst based on layered double hydroxides coated with copper nitrate [LDH@(3-chloropropyl)trimethoxysilane@N1,N4-bis(4,6-diamino-1,3,5-triazin-2-yl)benzene-1,4-disulfonamide@Cu] was successfully synthesized. The structure of the new synthesized catalyst was investigated and confirmed using different analytical techniques, such as Fourier-transform infrared spectroscopy (FTIR), energy-scattered X-ray spectroscopy (EDX) mapping, X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), and heat gravity/heat derivatization (TGA/DSC). The skilled catalyst proved its efficiency for one-pot three-component synthesis of pyrano[2,3-d]pyrimidine and new dihydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidine-dione derivatives. Using this efficient catalyst, products were synthesized with a high yield, in a short time, and under soft and solvent-free conditions. The catalyst can be recovered and reused four times without a significant loss of efficiency.

Ceric ammonium nitrate catalyzed one-pot three-component microwave-assisted synthesis of indole-substituted fused pyrimidine and pyridine derivatives

The study investigates the synthesis of fused pyridine and pyrimidine derivatives known for their diverse biological activities and structural versatility which serve as pivotal building blocks in organic synthesis. A series of indole-substituted cyanamide derivatives were synthesized by one-pot three-component cyclo-condensation between Indole-3-carboxaldehyde, malononitrile, and electron-rich aromatic and heterocyclic amines by employing several methods such as grinding, microwave irradiation and conventional reflux in the presence of ceric ammonium nitrate and DMF. The nuclei differ concerning the heterocyclic amines such as pyridine, pyrimidine, pyrazine, thiazole, and tetrazole. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and Mass spectra. The reaction proceeds via Knoevenagel condensation, Michael addition, and intramolecular cyclization. The employed methodology offers the convenient advantages of cascade one-pot condensation, easy isolation, short reaction time, and excellent yield (83–95%).

An efficient, green and micellar catalyzed preparative-scale synthesis of 3,4-Disubstituted isoxazole-5(4H)-ones in the water

The one-pot three-component synthesis of 3,4-Disubstituted isoxazole-5(4H)-ones has been developed using an aqueous micellar medium as a catalyst under milder reaction conditions. The reaction was completed by using 25 mol% of sodium lauryl sulfate in an aqueous medium at room temperature. The reaction employs a green solvent, an eco-friendly reagent, and a non-chromatographic method for purification. The present reaction tolerates several substituted aldehydes and has proved to be efficient along with excellent yield. Moreover, the micellar catalyst was recovered and reused several times without significantly losing its catalytic activity.