One-pot Multicomponent Reaction Research Articles

Immobilized Ni on TMEDA@βSiO2@αSiO2@Fe3O4: as a novel magnetic nanocatalyst for preparation of pyrido[2,3-d:6,5-d']dipyrimidines.

In the current body of research, a very quick and effectual procedure for the synthesis of pyrido[2,3-d:6,5-d']dipyrimidines has been developed. This method is accomplished through the one-pot multi-component reaction of 2-thiobarbituric acid, NH4OAc and aldehydes utilizing Ni-TMEDA@βSiO2@αSiO2@Fe3O4 as a novel mesoporous nanomagnetic catalyst at room temperature. This protocol is one of the few reports of the preparation of these derivatives without the use of conventional heating as well as energies such as microwave and ultrasound radiation. The characterization of the prepared catalyst was well accomplished by different techniques such as FT-IR, ICP-OES, SEM, TEM, BET, XRD, VSM, TGA, EDX and Elemental mapping. This organometallic catalyst was reusable for seven times with negligible decrement in its catalytic performance. In addition, all of the products were produced with high TON and TOF values, which demonstrates that our catalyst has a very high level of activity in the preparation of pyrido[2,3-d:6,5-d']dipyrimidines.

Synthesis, computational studies and biological evaluation of novel Acenaphthoquinone-imidazole derivatives as dual inhibitors of HSP90 and Topo II in cancer therapy

In this study, titled compounds (4a-4j) were synthesized by employing one-pot multicomponent reaction. To evaluate the binding affinity of derivatives against topo II/Hsp90 performed insilico molecular simulations. Using web tools ADMET and drug-likeness properties were predicted. The conjugation in the compound was confirmed by 1H NMR, 13C NMR, UV, Mass, and IR spectral studies. All the compounds showed the highest binding score compared to standard doxorubicin. These synthesized compounds exhibited moderate toxicities. The anticancer activity of the synthesized compounds was studied against cancer cell lines A-549(lung), HeLa (cervical), Du – 145 (prostate), Hep-G2 (liver) and one normal cell line (NHDF) using MTT assay. Among all the compounds 4a, 4e, 4f and 4i exhibited highly potent activity against all against cell lines compared to doxorubicin standard anticancer drug. The results propose that these compounds can act as leads to design dual inhibitors for cancer treatment.

Insights into the catalytic potential of a rationally designed magnetic boron nitride nanosheet supported nickel catalyst for the efficient synthesis of 1,4-dihydropyridines

Magnetically integrated ultrathin h-BN nanosheets based nickel catalyst for the one-pot multicomponent reaction to access 1,4-dihydropyridines.

Visible-light-initiated external photocatalyst-free synthesis of α,α-difluoro-β-ketoamides from 4-aminocoumarins.

A concise and efficient ring-opening difluorination strategy was developed for the synthesis of highly functionalized hydroxy-containing α,α-difluoro-β-ketoamides from the one-pot multicomponent reaction of 4-aminocoumarins, NFSI, and water in dimethyl carbonate (DMC) as a green solvent. The reactions were smoothly achieved under visible light irradiation in air at room temperature without the addition of any other external photocatalysts. With this protocol, various α,α-difluoro-β-ketoamides were successfully synthesized under mild conditions (25 examples, 73-91% yields). This transition-metal-free synthetic procedure shows good functional group compatibility and attractive practical potential for large-scale synthesis.

3-Phenyl-10-(2,3,4-trimethoxyphenyl)-9,10-dihydro-4H,8H-pyrano [2,3-f]chromene-4,8-dione

An efficient telescoped method for synthesis of 3-phenyl-10-(2,3,4-trimethoxyphenyl)-9,10-dihydro-4H,8H-pyrano[2,3-f]chromene-4,8-dione was elaborated. The presented protocol includes the one-pot multicomponent reaction of 7-hydroxy-3-phenyl-4H-chromen-4-one, 2,3,4-trimethoxybenzaldehyde and Meldrum’s acid. Advantages of this method are the application of readily available starting reagents, atom economy and easy procedure of preparation and purification of the target product. The structure of the synthesized polycyclic compound was proved by 1H, 13C-NMR, IR spectroscopy and high-resolution mass spectrometry with electrospray ionization (ESI-HRMS).

Synthesis of Novel Pyrimido[4,5-b] Quinolines Containing Benzyloxy and 1,2,3-Triazole Moieties by DABCO as a Basic Catalyst.

DABCO was used as a basic and inexpensive catalyst for the synthesis of some new benzyloxy pyrimido[4,5-b]quinoline derivatives and 1,2,3- triazole-fused pyrimido[4,5-b]quinolines by the one-pot multi-component reaction of various benzyloxy benzaldehydes or benzylic -1,2,3-triazol-4-yl-methoxy benzaldehydes with dimedone and 6-amino-1,3-dimethyluracil at 90 °C under the solvent-free condition.

Facile Synthesis and Biological Activity Investigation of New Spiropyridoindole Derivatives via Multicomponent Reactions of Acetylisatin

The Petasites hybridus rhizome water extract was used as green media for the preparation of the Ag/Fe3O4/CdO@MWCNTs magnetic nanocomposites and its activity was evaluated by using in the one-pot multi-component reaction of 1-acetylisatin, secondary amines, vinilidene Melderum’s acid, primary alcohols, malononitrile and isothiocyanate in aqueous media at room temperature for the production of novel derivatives of spiropyridoindole in excellent yields. Moreover, the reduction of organic pollutants such 4-nitrophenol (4-NP) was performed by synthesized Ag/Fe3O4/CdO@MWCNTs in water at room temperature. The outcomes showed this catalyst decreased organic pollutants in a few seconds. The synthesized spiropyridoindole has NH2 functional group that has acidic hydrogen and show high antioxidant activity. These synthesized compounds also displayed antimicrobial activity by using the disk diffusion procedure and two Gram-positive and Gram-negative bacteria. The employed process for production of spiropyridoindole has some benefits such as short time of reactions, excellent efficiency of product, easy separation of catalyst and products. Highlights Green chemistry is the use of a set of principles to reduce or eliminate the use or generation of unsafe materials in the design, fabrication, and applications of chemical products. Among solvents, water is a green solvent and very suitable for performing the organic reaction. The present procedure avoids the use of toxic solvents. In medicinal chemistry, the heterocyclic compounds have a well-known subject due to having a wide area of biological activities of these compounds. Therefore these compounds are very important and for the synthesis of these compounds existed many procedures.

Bioevaluation of synthetic pyridones as dual inhibitors of α‐amylase and α‐glucosidase enzymes and potential antioxidants

Herein, a library of novel pyridone derivatives 1-34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1-34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1-34 were structurally characterized by different spectroscopic techniques. Most of the tested compounds showed more promising inhibition potential than the standard acarbose (IC50 = 14.87 ± 0.16 µM) but compounds 13 and 12 were found to be the most potent compounds with IC50 values of 9.20 ± 0.14 µM and 3.05 ± 0.18 µM against α-amylase and α-glucosidase enzymes, respectively. Compounds 1-34 also displayed moderate antioxidant potential in the range of IC50 = 96.50 ± 0.45 to 189.98 ± 1.00 µM in comparison to the control butylated hydroxytoluene (BHT) (IC50 = 66.50 ± 0.36 µM), in DPPH radical scavenging activities. Additionally, all synthetic derivatives were subjected to a molecular docking study to investigate the interaction details of compounds 1-34 (ligands) with the active site of enzymes (receptors). These results indicate that the newly synthesized pyridone class may serve as promising lead candidates for controlling diabetes mellitus and as antioxidants.

Design of an efficient three component one-pot synthesis of -1,2,3,4-tetrahydro-4-oxo-6-(5-substituted 2-phenyl-1H-indol-3-yl)-2-thioxopyrimidine-5-carbonitrile as antimicrobial and antitubercular agent

In the present study, a novel, rapid, improved and eco-friendly synthesis of indolyl-pyrazolo-pyrimidine derivatives 4a-c by using conventional method via one-pot multi-component reaction has been described. The structures of all these unknown compounds have been confirmed with the help of physical and spectroscopic techniques like IR, 1H and 13C NMR and mass spectrometry and these newly synthesized compounds have been evaluated for in vitro antimicrobial and antitubercular and antioxidant activities. The results reveal that compound 4a exhibits promising antimicrobial, antitubercular and antioxidant properties when compared to the standard drugs.

Design, Synthesis and In Vitro Evaluation of Spirooxindole-Based Phenylsulfonyl Moiety as a Candidate Anti-SAR-CoV-2 and MERS-CoV-2 with the Implementation of Combination Studies.

The search for an effective anti-viral to inhibit COVID-19 is a challenge for the specialized scientific research community. This work investigated the anti-coronavirus activity for spirooxindole-based phenylsulfone cycloadducts in a single and combination protocols. The newly designed anti-SARS-CoV-2 therapeutics spirooxindoles synthesized by [3 + 2] cycloaddition reactions represent an efficient approach. One-pot multicomponent reactions between phenyl vinyl sulfone, substituted isatins, and amines afforded highly stereoselective anti-SARS-CoV-2 therapeutics spirooxindoles with three stereogenic centers. Herein, the newly synthesized spirooxindoles were assessed individually against the highly pathogenic human coronaviruses and proved to be highly potent and safer. Interestingly, the synergistic effect by combining the potent, tested spirooxindoles resulted in an improved antiviral activity as well as better host-cell safety. Compounds 4i and 4d represented the most potent activity against MERS-CoV with IC50 values of 11 and 23 µM, respectively. Both compounds 4c and 4e showed equipotent activity with the best IC50 against SARS-CoV-2 with values of 17 and 18 µM, respectively, then compounds 4d and 4k with IC50 values of 24 and 27 µM, respectively. Then, our attention oriented to perform a combination protocol as anti-SARS-CoV-2 for the best compounds with a different binding mode and accompanied with different pharmacophores. Combination of compound 4k with 4c and combination of compounds 4k with 4i proved to be more active and safer. Compounds 4k with 4i displayed IC50 = 3.275 µM and half maximal cytotoxic-concentration CC50 = 11832 µM. MD simulation of the most potential compounds as well as in silico ADMET properties were investigated. This study highlights the potential drug-like properties of spirooxindoles as a cocktail anti-coronavirus protocol.

Magnesium Sulphate-Catalyzed Green and Efficient Synthesis of Some New Derivatives of 1-Amido Alkyl Naphthols under Solvent-Free Conditions

Abstract: The present work describes an efficient, green, and direct approach for the synthesis of amido alkyl naphthols via one-pot multicomponent solvent-free reaction (MCR) of substituted aromatic aldehydes, β-naphthols, and urea by the use of easily available, non-toxic, and cost-effective Lewis acid catalyst magnesium sulphate (MgSO4.7H2O). The important characteristics of this reaction include the following: eco-friendly and mild reaction conditions, excellent yields of the products, shorter reaction time, economically cheaper and environmentally friendly catalyst MgSO4.7H2O. Also, clean reaction, non-column purification, and operational simplicity are some of the additional significant features of this approach.

Synthesis and evaluation of the antioxidant activity of new spiro-1,2,4-triazine derivatives applying Ag/Fe3O4/CdO@MWCNT MNCs as efficient organometallic nanocatalysts.

We applied the Petasites hybridus rhizome water extract as green media so that Ag/Fe3O4/CdO@ multi-walled carbon nanotubes magnetic nanocomposites (Ag/Fe3O4/CdO@MWCNTs MNCs) could be prepared. We also evaluated its activity by using in the one-pot multicomponent reaction of acetophenones, diethyl oxalate, ammonium acetate, and activated carbonyl compounds such as ninhydrin, isatin and acenaphthylene-1,2-dione, and malononitrile and hydrazoyl chlorides in an aqueous medium at room temperature for the generation of spiro-1,2,4-triazines as new derivatives with tremendous output. Moreover, reducing organic pollutants from 4-nitrophenol (4-NP) was carried out by generating Ag/Fe3O4/CdO@MWCNTs in water at room temperature. The results displayed that Ag/Fe3O4/CdO@MWCNTs reduced pollutants of organic compounds in a short time. The synthesized spiro-1,2,4-triazines have NH and OH functional groups having acidic hydrogen with high antioxidant power. Also, the spiro-1,2,4-triazines exhibited antimicrobial ability. For this purpose, the disk diffusion method was applied and two kinds of bacteria, Gram-positive and Gram-negative, were employed for the analysis. Furthermore, we applied functional theory-based quantum chemical methods in order to better understand reaction mechanism density. To generate spiro-1,2,4-triazines, the applied process showed many properties such as reactions with short time, products with good yields, and simple extraction of catalyst from a mixture of reactions.

Synthesis of steroidal dihydropyrazole derivatives using green ZnO NPs and evaluation of their anticancer and antioxidant activity

Zinc oxide nanoparticles (ZnO NPs) were synthesized by a green method using Azadirachta indica leaf extract. The structure of the prepared ZnO (NPs) were characterized by FT-IR, XRD, SEM-EDX and TEM analyses. The biosynthesized ZnO (NPs) were then used as a catalyst for the synthesis of steroidal dihydropyrazole derivatives through a one-pot multicomponent reaction involving phenyl acetylene and hydrazine derivatives. The anticancer activity of newly synthesized compounds were evaluated against three cancer cell lines namely HeLa (human cervical carcinoma), Hep3B (human hepatocellular carcinoma) and MCF7 (human breast adenocarcinoma) by MTT assay. The tested compounds were found to be active against all cancer cell lines and less toxic towards normal peripheral blood mononuclear cells (PBMCs). Antioxidant activity have also been investigated via free radical scavenging ability using DPPH, FRAP and ABTS assay. The tested compounds were found to exhibit moderate to good antioxidant activity which increases with increase in the concentration of steroidal dihydropyrazoles. Among all the tested steroidal dihydropyrazoles, compound 17 is found to be most active.

Six-component synthesis and biological activity of novel spiropyridoindolepyrrolidine derivatives: A combined experimental and theoretical investigation.

Petasites hybridus rhizome water extract was used as green media for the preparation of Ag/Fe3O4/CdO@multi-walled carbon nanotubes magnetic nanocomposites (Ag/Fe3O4/CdO@MWCNTs MNCs), and its activity was evaluated by using in the one-pot multicomponent reaction of isatins, acetyl chloride, secondary amines, vinilidene Meldrum’s acid, primary amines, and malononitrile in an aqueous medium at room temperature for the generation of spiropyridoindolepyrrolidine as new derivatives with tremendous output. In addition, organic pollutant reduction of 4-nitrophenol (4-NP) was carried out by generated Ag/Fe3O4/CdO@MWCNTs in water at room temperature. The results displayed that Ag/Fe3O4/CdO@MWCNTs were reduced as pollutants of organic compounds in a short time. The synthesized spiropyridoindolepyrrolidine has an NH2 functional group that has acidic hydrogen and shows high antioxidant ability. Also, the spiropyridoindolepyrrolidine exhibited antimicrobial ability, and the method that is used for this purpose is the disk diffusion method, and two kinds of bacteria, Gram-positive and Gram-negative, were employed for this analysis. Also, to better understand the reaction mechanism density, functional theory-based quantum chemical methods have been applied. For the generation of spiropyridoindolepyrrolidine, the used process has many properties such as reactions with short time, product with good yields, and simple extraction of catalyst from the mixture of reaction.

New ecofriendly heterogeneous nano-catalyst for the synthesis of 1-substituted and 5-substituted 1H-tetrazole derivatives

A novel ecofriendly heterogeneous catalyst containing Schiff base coordinated Cu(II) covalently attached to Fe3O4@SiO2 nanoparticles through imidazolium linker [Fe3O4@SiO2-Im(Br)-SB-Cu (II)] was synthesized and characterized by using various techniques. The catalytic efficiency of this nano-catalyst was tested in water in the synthesis of tetrazole derivatives using two one-pot multicomponent reaction (MCR) models: The synthesis of 1-aryl 1H-tetrazole derivatives from the reaction of aniline, triethyl orthoformate, and sodium azide and the synthesis of 5-aryl 1H-tetrazole derivatives from the reaction of benzaldehyde, hydroxy amine hydrochloride, and sodium azide. The investigation showed that (i) The catalyst is highly efficient in the synthesis of tetrazole derivatives with high yield (97%) in aqueous medium and mild temperatures; (ii) The catalytic effectiveness is due to the synergy between the metallic center and the imidazolium ion and (iii) The reuse advantage of the catalyst without contamination or significant loss (12% of loss range) in the catalytic activity.

A Three-Component Approach to (Hetero)arenes with Two N-Containing Heterocycle Motifs

AbstractA one-pot, three-component reaction involving SNAr-decarboxylative redox isomerization starting from an electron-withdrawing group bearing fluorobenzaldehyde or fluorothiophenecarbaldehyde (electron-pair diacceptor), secondary amine, and trans-4-hydroxy-l-proline or indoline-2-carboxylic acid (electron-pair donor) has been developed to give N-[(pyrrolylmethyl)-substituted (het)aryl]- and N-[(indolyl­methyl)-substituted (het)aryl]pyrrolidines, -piperidines, -morpholines, and -azocanes. The highlights of this protocol are its great convenience in the simultaneous construction of a C(sp2)–N bond and a C(sp3)–N bond with simple operation; the reaction can be performed on a gram scale. This efficient one-pot multicomponent reaction has potential as a novel method for drug synthesis, especially involving polycyclic compounds.

Green Synthesis and Study of Biological Activity of New Benzopyrimidoazepines: Reduction of Organic Pollutants Using Synthesized Fe3O4/TiO2/CuO@MWCNTs MNCs

In this work rhizome of Petasites hybridus was used for preparing water extract and utilized as green media for generating Fe3O4/TiO2/CuO@ Multi-Walled Carbon Nanotubes (MWCNTs) magnetic nanocomposites and its activity was evaluated by using in the one-pot multicomponent reactions (MCRs) of anilines, diethyl oxalate, activated acetylenic compounds, α-haloketones, ammonium acetate and aroyle(alkaloyl)isocyanates in aqueous at room temperature to produce of novel benzopyrimidoazepine derivatives in excellent yields. Moreover, the reduction of organic pollutants such 4-nitrophenol (4-NP) was performed by synthesized Fe3O4/TiO2/CuO@MWCNTs in H2O at room temperature. The outcomes showed this catalyst was decreased organic contaminants in the low time. The generated benzopyrimidoazepines have hydroxyl and two NH functional groups that have acidic hydrogen and show high antioxidant activity. The antioxidant activity order of some synthesized compounds was as TBHQ ≈ BHT>7b>7d>7c>7a. Also, antimicrobial ability of obtained benzopyrimidoazepines was investigated with the disk diffusion method, and two Gram-negative and Gram-positive bacteria and compounds 7b, 7c, 7e, and 7g have maximum effect on Escherichia coli relative to Gram positive and negative bacteria due to good diameter of inhibition zone. The short time of reactions, excellent efficiency of product, easy separation of catalyst and products employed process to the synthesis of benzopyrimidoazepines are some advantages of this procedure. HIGHLIGHTS Green chemistry is the use of a set of principles to reduce or eliminate the use or generation of unsafe materials in the design, fabrication, and applications of chemical products. Among solvents, water is a green solvent and very suitable for performing the organic reaction. The present procedure avoids the use of toxic solvents. Heterocyclic compounds hold a prominent position in medicinal chemistry owing to their wide spectrum of biological activities, such as antimalarial, antimicrobial, antitumor, anticancer, antidepressant, antiviral, antidiabetic, anti-inflammatory, and anti-HIV. The benzoazepine skeleton is a famous pharmacophore that is existed in several behavioral disorder drugs, such as imipramine, diazepam, and lorazepam.

An Efficient Synthesis and Study of Biological Activity of New Pyrimidoazepines Using Ag/Fe3O4/TiO2/CuO@MWCNTs Magnetic Nanocomposites: A Combined Experimental and Theoretical Investigation

In this research, we studied the one-pot multicomponent reaction of isatoic anhydride, electron deficient acetylenic compounds, α-haloketones, ammonium acetate, carbodiimides and Ag/Fe3O4/TiO2/CuO@MWCNTs magnetic nanocomposites as catalyst in aqueous at room temperature for the production of novel derivatives of pyrimidoazepines in excellent yields. Moreover, reduction of organic pollutants such 4-nitrophenol (4-NP) was performed by synthesized Ag/Fe3O4/TiO2/CuO@MWCNTs in water at room temperature. The outcomes showed this catalyst was decreased organic pollutants in few seconds. The synthesized pyrimidoazepines have OH and NH functional groups that have acidic hydrogen and show high antioxidant activity. These synthesized compounds also displayed antimicrobial activity by using the disk diffusion procedure and two Gram-positive and Gram-negative bacteria. Also, to better understand the reaction mechanism density functional theory (DFT) based quantum chemical methods have been applied. The employed process for the production of pyrimidoazepines has some benefits such as short time of reactions, excellent efficiency of product, easy separation of catalyst and products.

Synthesis and Biological Activity Investigation of New Oxazolopyrimidoazepine Derivatives: Application of Ag/Fe3O4/TiO2/CuO@MWCNTs MNCs in the Reduction of Organic Pollutants

Ag/Fe3O4/TiO2/CuO@MWCNTs magnetic nanocomposites were synthesized by the Petasites hybridus rhizome water extract as green media and used for one-pot multicomponent reaction of isatins, electron deficient acetylenic compounds, α-haloketones, ammonium acetate, tert-butyl isocyanide and ethyl bromopyruvate in aqueous media at room temperature for the production of novel derivatives of oxazolopyrimidoazepines in excellent yields. The synthesized oxazolopyrimidoazepines have OH and NH functional groups that have acidic hydrogen and show high antioxidant activity. Moreover, reduction of organic pollutants such 4-nitrophenol (4-NP) was performed by synthesized Ag/Fe3O4/TiO2/CuO@MWCNTs in water at room temperature. The outcomes showed this catalyst was decreased organic pollutants in few seconds. The employed process for the production of oxazolopyrimidoazepines has some benefits such as short time of reactions, excellent efficiency of product, easy separation of catalyst and products. HIGHLIGHTS Green chemistry is the use of a set of principles to reduce or eliminate the use or generation of unsafe materials in the design, fabrication and applications of chemical products. Among solvents, water is a green solvents and very suitable for performing organic reaction. The present procedure avoids the use of toxic solvent. Some representatives of this class of azaheterocycles are known as antiviral agents, glycosidase inhibitors, anticancer agents or antidiabetics. Therefore, in view of their medicinal relevance, an increasing number of synthetic methods have been described in recent years for the construction of highly substituted azepine derivatives.

Iodine/TBHP-Mediated One-Pot Multicomponent Protocol for Tandem C-N and C-S Bond Formation To Access Sulfenylimidazo[1,5-a]pyridines via C-H Functionalization.

A mild and simple protocol has been established for the formation of sulfenylated imidazo[1,5-a]pyridines. This is a metal-free iodine/TBHP-mediated one-pot multicomponent reaction, which follows C-H functionalization of the imidazo[1,5-a]pyridine skeleton formed during the reaction and its subsequent sulfenylation in the same step to offer sulfenylated imidazo[1,5-a]pyridines in good to high yields. The extension and applications of this method have also been demonstrated.