One-pot Multicomponent Synthesis Research Articles

Synthesis of pyrano[2,3‐d]pyrimidines and pyrido[2,3‐d]pyrimidines in the magnetized deionized water based on UV–visible study

A green synthetic route to the facile one-pot multicomponent synthesis of pyrano[2,3‐d]pyrimidines and pyrido[2,3‐d]pyrimidines have been developed using magnetized deionized water (MDW) as a green solvent under catalyst-free conditions. All reactions carried out in a short period of time and the products are obtained in high-to-excellent yields. The developed synthetic technique offers numerous advantages including eco-friendly, clean synthesis, simplicity, low cost, short reaction times, high reaction yields, and easy workup compared to the traditional synthetic method. Moreover, the reaction rates were followed spectrophotometrically by monitoring the changes in the absorption spectrum of the reaction mixture in ordinary deionized water and MDW.

Microwave-Accelerated Facile Synthesis of 1H-Pyrazolo[1,2-b]Phthalazine-5,10-Dione Derivatives Catalyzed by WEMPA

An efficient and rapid one-pot multicomponent synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones through condensation of aldehyde, malononitrile and phthalhydrazide catalyzed by agro-waste solvent catalyst-derived water extract of mango peel ash (WEMPA) under microwave irradiation is described. Further, the catalyst is prepared from agricultural waste and characterized for elemental composition by different techniques such as SEM-EDX, XRD and flame photometry. This green synthetic approach offers various advantages such as inexpensive, abundantly available source, shorter reaction time (6–8 min), good-to-excellent yield (83%–89%), simple workup and a sustainable alternative method to the existing protocols. All the synthesized compounds (4a–l) was confirmed by FT-IR, 1H-NMR, 13C-NMR and LC-MS.

Synthesis of 3,4-dihydropyrimidinones using nano γ-Al2O3/BF3/Fe3O4 as an efficient magnetic nanocatalyst under solvent-free conditions

Nano-γ-Al2O3/BF3/Fe3O4 magnetic nanoparticles was synthesized and characterized with Fourier Transform Infrared (FT-IR), Powder X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Transmittance Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM), Brunauer–Emmett–Teller (BET) and Thermal Gravimetry (TGA). Dihydropyrimidinones (DHP) act as antivirals, antibacterial, antifungal, antiinflammatory, antioxidan, anticarcinogen, calcium channel blockers, antihypertensive, anti-cancer and anti-HIV compounds. Nano-γ-Al2O3/BF3/Fe3O4 magnetic nanoparticles as an efficient catalyst was applied for the mild and green one-pot multicomponent synthesis of 3,4-dihydro pyrimidine-2(1H)-ones/thiones under solvent-free conditions. Biginelli reaction proceeds through an aldehyde, β-keto ester and urea or thiourea to the dihydropyrimidinone. Excellent yields of dihydropyrmidinones are gained within a short reaction time. The proposed method offers several advantages such as short reaction time, high efficiency, smooth purification, cleaning reaction, ease of recovery, and reusable catalyst. The structure and purity of these compounds were confirmed using IR and 1H NMR and 13C NMR spectral analysis. Meanwhile, the physical property of products were compared with reported ones.

ZnFe2O4 Nano-Catalyzed One-Pot Multi-Component Synthesis of Substituted Tetrahydropyranoquinoline under Neat Ultrasonic Irradiation

ZnFe2O4 nano-catalyzed facile synthesis of tetrahydropyranoquinoline derivatives (4a–f) via one-pot multi-component Povarov’s inverse-electron-demand hetero Diels–Alder reaction of substituted aromatic aldehyde (1), aromatic amine (2) with dihydrofuran (3) under ultrasonic irradiation. This may be helpful to society to get more active pharmaceutical ingredients. In the present study, a series of tetrahydroquinoline (4a–f) were synthesized and confirmed with several spectral characterization techniques. Synthetic approach of present research toward the synthesis of THQ was significantly shown that ZnFe2O4 plays a vital role in highly efficient, eco-friendly, recyclable heterogeneous nano-catalysts. This resulted in enhancing reaction rate, solvent-free reaction, easy to carry, simple isolation, and high yielded product.

New antibacterial cadiolide analogues active against antibiotic-resistant strains

The synthesis of new cadiolide analogues was carried out using a one-pot multi component synthesis. The antibacterial activity of these molecules was evaluated on standard and antibiotic resistant bacterial strains chosen for their involvement in human health or in food-born poisoning. Four molecules have shown good activities with MICs of 2 μg/mL−1. The introduction of an indole group or the conversion of the lactone into lactam have highlighted two new families of molecules with promising antibacterial activity. In addition, most of these active molecules are devoid of cytotoxic activity against keratinocyte cells.

Sonosynthesis of Spiro-Oxindoles Using Crosslinked Sulfonated Polyacrylamide Tethered to nano-Fe3O4 as High Performance Catalyst

Crosslinked sulfonated polyacrylamide (Cross-PAA-SO3H) tethered to nano-Fe3O4 as a superior heterogeneous solid acid catalyst has been used for the preparation of eight spiro-oxindoles by reactions of phenylhydrazine or hydrazine hydrate, isatins, ketoesters and naphthylamine or 2-naphthol under ultrasonic irradiations. The present catalytic procedure is extensible to a wide diversity of substrates for the synthesis of a variety-oriented library of oxindoles. The structures of the prepared oxindoles were fully characterized by 1H and 13C NMR spectra, FT-IR spectra, and elemental analysis. Experimental simplicity, wide range of products, excellent yields in short reaction times, reusability of the catalyst, low catalyst loading and use of ultrasonic irradiation, are some of the substantial features of this method. The feasibility of performing one-pot multi-component synthesis under ultrasonic irradiation with a heterogeneous catalyst could improve the reactions rates and shorten the reactions times.

One-pot multi-component synthesis of new bis-pyridopyrimidine and bis-pyrimidoquinolone derivatives

A variety of bis-heterocycles such as bis(pyrimido[4,5-b]quinolone), bis(chromeno[3′,4':5,6]pyrido[2,3-d]pyrimidine), bis(pyrido[2,3-d:6,5-d']dipyrimidine), and bis(benzo[g]pyrimido[4,5-b]quinolone) derivatives were synthesized via one-pot, multi-component reaction of various 6-aminouracils or 6-aminothiouracils, terephthalaldehyde, and CH-acids such as 4-hydroxycoumarin, dimedone, 2-hydroxy-1,4-naphthoquinone, barbituric acid, and thiobarbituric acid in EtOH as a solvent at reflux. The mild conditions, fast rate of reaction, absence of catalyst, different functional group compatibility, simple operation and work-up involving no chromatographic process, are worth mentioning.

Ag NPs on chitosan-alginate coated magnetite for synthesis of indazolo[2,1-b]phthalazines and human lung protective effects against α-Guttiferin

Biocomposite nanomaterials have been evolved as the new generation catalysts and therapeutic supplement in these days. Magnetically isolation has added new features to this category. This has encouraged us to synthesize a novel Ag NP adorned chitosan-alginate dual bio-polysaccharide (two of the more versatile polysaccharides) modified core-shell magnetic nanocomposite (Fe3O4/CS-Alg/Ag NPs). The material was meticulously characterized following different physicochemical techniques, such as, FT-IR, ICP-OES, FESEM, EDX, atomic mapping, TEM, VSM, XRD and XPS studies. The as synthesized material was catalytically explored in the one-pot multicomponent synthesis of biologically potent 2H-indazolo[2,1-b]phthalazine-trione derivatives involving a wide range of substrates. The reactions were ended up with excellent yields under solvent-free heating conditions. The catalyst recyclability, heterogeneity and leaching tests were performed to ensure its high stability and robustness. It could be reused as much as 10 times in succession with almost unchanged catalytic performances. In the lung protective part of the present research, the human lung toxicity was induced by α-Guttiferin. The cell viability of lung MRC-5, CCD19Lu, WI-38, and BEAS-2B cell lines was measured by trypan blue assay. Caspase-3 activity was assessed by the caspase activity colorimetric assay kit and mitochondrial membrane potential of lung cells was studied by Rhodamine123 fluorescence dye. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test was used to show DNA fragmentation and apoptosis of lung cells. Also, the Rat inflammatory cytokine assay kit was used to measure the concentrations of inflammatory cytokines. The catalyst-treated cell cutlers significantly (p ≤ 0.01) reduced the DNA fragmentation, caspase-3 activity, and inflammatory cytokines concentrations, and raised the mitochondrial membrane potential and cell viability in the high concentration of α-Guttiferin-treated lung MRC-5, CCD19Lu, WI-38, and BEAS-2B cells. The best result of lung protective properties of catalyst against α-Guttiferin was seen in the high dose of catalyst i.e., 4 μg. DPPH test revealed similar antioxidant potentials for catalyst and butylated hydroxytoluene. The catalyst inhibited half of the DPPH molecules in the concentration of 171 μg/mL. According to the above results, catalyst can be administrated as a lung protective drug for the treatment of lung diseases after approving in the clinical trial studies in humans.

Ionic liquid mediated one-pot multicomponent synthesis of methyl 1,2-diaryl-4-hydroxy-5-oxo-2,5-dihydro-1h-pyrrole-3-carboxylates

Abstract A simple, efficient, eco-friendly and a green synthetic method has been developed for the synthesis of polysubstituted pyrrolidinone derivatives via one-pot multi component reaction of aromatic aldehydes, aromatic amines with dimethyl but-2-ynedioate by using inexpensive nontoxic ionic liquid [bmim]BF4 under PEG-400 medium. The present methodology offers more environmental acceptability, higher yields with very shorter reaction time and recyclability of the ionic liquid.

One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents.

Mankind has always suffered from multiple diseases. Therefore, there has been a rigorous need in the field of medicinal chemistry for the design and discovery of new and potent molecular entities. In this work, thirteen tetrahydroquinoline derivatives were synthesized and evaluated biologically for their antioxidant, α-amylase enzyme inhibitory, anti-proliferative and anti-inflammatory activities. SF8 showed the lowest IC50 of 29.19 ± 0.25 µg/mL by scavenging DPPH free radicals. SF5 showed significant antioxidant activity in total antioxidant capacity (TAC) and total reducing power (TRP) assays. SF5 and SF9 showed the maximum inhibition of α-amylase enzyme i.e., 97.47% and 89.93%, respectively, at 200 µg/mL concentration. Five compounds were shortlisted to determine their anti-proliferative potential against Hep-2C cells. The study was conducted for 24, 48 and 72 h. SF8 showed significant results, having an IC50 value of 11.9 ± 1.04 µM at 72 h when compared with standard cisplatin (IC50 value of 14.6 ± 1.01 µM). An in vitro nitric oxide (NO) assay was performed to select compounds for in vivo anti-inflammatory activity evaluation. SF13 scavenged the NO level to a maximum of 85% at 50 µM concentration, followed by SF1 and SF2. Based on the NO scavenging assay results, in vivo anti-inflammatory studies were also performed and the results showed significant activity compared to the standard, acetylsalicylic acid (ASA).

Zirconium tetrachloride catalyzed one-pot highly efficient green synthesis of functionalized piperidines under visible light

Abstract Highly efficient multicomponent one-pot green synthesis of a series of pharmaceutically interesting functionalized piperidine derivatives has been developed based on a low-cost and eco-friendly zirconium tetrachloride catalyst via tandem reactions of 1,3-dicarbonyl compounds, aromatic aldehydes, and various amines in ethanol under visible light. High atom-economy, high yields, less reaction times, eco-friendly, and mild reaction conditions are some of the important features of this protocol. Key words: ZrCl 4 , piperidines, multi-component reactions, visible light

Hollow Mesoporous Silica Sphere (HMSS) as a Recyclable Nano-catalyst in an Efficient One-Pot Multicomponent Synthesis of 2-Amino-3-Cyano-4H-Pyran Derivatives

Mesoporous material has a significant role in medicine, health care, environmental monitoring, sensing the hazardous agents, and fighting against viruses and bacteria. Nano-silica sphere is an important member of the mesoporous family that noticeably flourished in biology, health care, and other industrial applications. Efficient one-pot multicomponent syntheses of 2-amino-3-cyano-4H-pyran derivatives were carried out over readily available and simply synthesized recyclable Hollow Mesoporous Silica Sphere (HMSS). Comparable yields were encountered with better efficiency, lower cost, and shorter reaction time. Hence, superior catalytic activity, flexibility, ease of recovery, tuneable hole size, and high surface to volume ratio were the major characteristics of the catalyst which distinguish this protocol from previously reported ones. The catalyst was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) techniques, and nitrogen absorption and desorption (BET) analyses. The results showed that the synthesizing of HMSS catalysts under a mild and green condition in which comparable yields were encountered with better efficiency, lower cost, and shorter reaction with other major economic advantages.

Densely functionalized cinnolines: Controlled microwave-assisted facile one-pot multi-component synthesis and in vitro anticancer activity via apoptosis induction.

There is an urging continuous need for novel anti-cancer agents due to persistent chemoresistance. Herein, newly synthesized cinnolines are evaluated for their possible anticancer activities and suggested mechanisms. In the current study, a simple and efficient synthesis of densely functionalized cinnolines has been developed that relied on multi-component reaction of ethyl 5-cyano-4-methyl-1-aryl-6-oxo-1,6-dihydropyridazine-3-carboxylates with aromatic aldehydes and nitromethane in dioxane/pipridine under controlled microwave heating. Selected cinnolines (4a-c, e, h, j-n, q-v) were tested for possible anticancer activity using in vitro one dose assay at National Cancer institute, USA. Only cinnoline 4b stood out as the most potent cinnoline derivative (mean GI%=26.33) with broad-spectrum antitumor activity against the most tested cancer cell lines from all subpanels. The target cinnoline 4b emerged as the most active derivative against both leukemia RPMI-8226 and melanoma LOX IMVI cell lines (GI% = 106.06 and 82.1) respectively, with IC50 values equal to 17.12±1.31 and 12.32±0.75μg/mL, which are comparable to those of staurosporin; 24.97±1.47 and 8.45±0.42μg/mL, respectively. Cinnoline 4b influenced cell cycle distribution causing pre-G1 apoptosis and cell growth arrest at G2/M phase. It also induced apoptosis in both cell lines as manifested by significant increase in the percent of annexin V-FITC positive apoptotic cells in leukemia RPMI-8226 cells (from 1.09% to 12.47%) and melanoma LOX IMVI (from 1.32% to 19.05%). In addition, it showed lower expression levels of anti-apoptotic Bcl-2 protein, and higher expression levels of pro-apoptotic proteins; Bax, p53, cytochrome c, caspases 3 and 9. CONCLUSION: Induction of mitochondrial intrinsic pathway of apoptosis is a possible mechanism by which cinnoline 4b may confer its anticancer activity.

Green one-pot multicomponent synthesis, biological evaluation and theoretical investigations of some novel β-acetamido ketone derivatives as potent cholinesterase inhibitors

A series of novel β-acetamido ketones have been prepared via a four-component condensation between aromatic aldehydes, enolizable ketones, acyl chloride and acetonitrile in the presence of 10 mol% of phenylboronic acid as a catalyst. The expected products have been obtained in good to excellent yields. In addition, in vitro cholinesterase inhibitory activity of title compounds has been studied and the results indicated that some compounds exhibited remarkable BChE activity. In order to gain insights into the molecular structure and chemical reactivity of the synthesized β-acetamido ketones, density functional theory (DFT) calculations were also carried out.

(E)-2-(2-Allylidenehydrazinyl)thiazole derivatives: Design, green synthesis, in silico and in vitro antimycobacterial and radical scavenging studies.

By understanding the rampant infections of Mycobacterium tuberculosis (Mtb) and inflammations caused due to the generation of radical species during the Mtb infection, a series of (E)-2-(2-allylidenehydrazinyl)thiazole derivatives, with dual-action properties, was designed. The molecules were designed with a considerable variation in LogP, one of the critical parameters in physicochemical properties, and analyzed for their drug-likeness. For the synthesis, a simple, green, and multicomponent one-pot synthesis method was developed. The in vitro inhibition potentials were evaluated against Mtb H37 Rv by the microplate Alamar Blue assay. The results reveal that compound 6 was potent, with a MIC value of 6.5 µg/ml, and showed better interactions with the KasA protein with binding free energy (ΔG) of -9.4 kcal/mol. Also, the radical scavenging properties were studied to establish the dual-action properties of the molecules. Compound 9 exhibited promising antioxidant and nitric oxide radical scavenging activities, with 81.7% and 81.0%, respectively, at 1,000-μg/ml concentration.

One-Pot Multicomponent Synthesis and Anticancer Activity of 1,3-Cyclopentathiazine and Pyrimidothiazine Derivatives

Novel 1,3-cyclopentathiazine and pyrimidothiazine derivatives were synthesized starting from 7-benzyl-4-phenylcyclopenta[d][1,3]thiazin-2-amine (CTA) prepared by a one-pot multicomponent reaction of cyclopentanone, benzaldehyde, and thiourea. Cyclocondensation of CTA with benzylidenemalononitrile gave a pyrimidothiazine. Oxidation of cyclopentathiazine with hydrogen peroxide afforded the corresponding epoxide, while its alkylation with ethyl iodide yielded an N-ethyl derivative. Cyclopentylidenemalononitrile was reacted with formaline and carbon disulfide to obtain pyridine-4-carbonitrile and thiapyrane, respectively, and the reactions of cyclopentylidenemalononitrile with aryl isocyanate and aryl isothiocyanate gave condensed diimino-substituted cyclopentanaphthyridine-1,6-dione and dithiaacenaphthylene-3,8-diylidedibenzamide, respectively. Heating cyclopentanone with benzoyl isothiocyanate and benzoyl chloride produced a sulfide derivative and an enolic dione, respectively. The structures of the newly synthesized compounds were confirmed by spectral analysis, and some products were screened for anticancer activity.

Solvent-Free Microwave Assisted Synthesis of Novel Pyrazole-Oxopyrrolidine and Pyrazole-Oxopiperidine Derivatives and Their Antimicrobial Activity

Herein we report an efficient one-pot multicomponent synthesis of novel pyrazole-oxopyrrolidine derivatives via the Ugi (4C3C) reaction under MW solvent-free conditions. The structures of products have been characterized by FTIR, 1H and 13C NMR, and mass spectrometry, and HPLC analysis. All synthesized compounds have been tested for their antimicrobial activity and some of those characterized as highly active.

One-Pot Multicomponent Reaction of Catechols, Ammonium Acetate, and Aldehydes for the Synthesis of Benzoxazole Derivatives Using the Fe(III)-Salen Complex.

The Fe(III)-salen complex has been applied successfully as a catalyst for the novel, simple, efficient, and one-pot multicomponent synthesis of benzoxazole derivatives from catechols, ammonium acetate as the nitrogen source, and aldehydes (nontoxic and cheap alternatives of amines) for the first time. Using this procedure, a wide range of benzoxazoles was successfully synthesized in the presence of a catalyst in EtOH under mild conditions, and all products were obtained in excellent yields. To the best of our knowledge, this method is the first example of the multicomponent synthesis of benzoxazole derivatives using these starting materials. The notable features such as the use of air that is considered as a benign oxidant and EtOH as a green solvent, ease of product separation, readily available and inexpensive aldehydes, and mild conditions make our procedure more efficient and practical for organic synthesis. Moreover, the current protocol is successfully applied to synthesize desirable products on a large scale.

Sodium L-ascorbate-catalyzed one-pot green synthesis of sulfonyl substituted 2-amino-4H-pyran derivatives

In the present research, multicomponent one-pot green synthesis of sulfonyl-substituted 2-amino-4H-pyran derivatives through the reaction of aromatic aldehyde, cyclic ketone and phenyl (or methyl) sulfonyl acetonitrile was developed. This multicomponent reaction distinguishes by employing a less expensive and non-toxic sodium L-ascorbate as a catalyst which represents a simple, efficient and environmentally benign route to obtain sulfonyl substituted 2-amino-4H-pyran derivatives in moderate to good yields. The major advantages of the present work are high efficiency, short reaction time, use of cheap, safe and stable catalyst system as well as green solvent and mild reaction condition. Herein, we introduce an efficient and green multicomponent one-pot protocol for the synthesis of sulfonyl-substituted 2-amino-4H-pyran derivatives in 80% EtOH using sodium L-ascorbate (NaAsc) as catalyst.

A highly efficient one-pot multicomponent synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones catalyzed by strontium pyroarsenate nano-plates

The present work describes the one-pot multicomponent synthesis of heterocyclic 3,4-dihydropyrimidin-2-(1H)-ones and thiones (DHPMs) under solvent-free conditions by Sr2As2O7 nanocatalyst. Sr2As2O7 nanocatalyst was synthesized by solvothermal reactions at stoichiometric molar ratio. The characterizations of the as-prepared nanomaterials were performed by X-ray powder diffraction (XRPD) and fourier-transform infrared (FTIR) techniques. According to Rietveld analysis data, it was found that reaction time had a considerable effect on crystal phase change from monoclinic to tetragonal crystal system. Field emission scanning electron microscope (FESEM) images showed that the morphology of the obtained materials was changed by increasing the reaction time, from 24 to 120 h, from long-length rods to multigonal plates. Catalytic activity of the nanomaterials was investigated in Biginelli reactions for the synthesis of heterocyclic DHPMs compounds. The synthesis yields at optimum conditions were 94% and 96% for S1 and S5, respectively. Langmuir–Hinshelwood kinetic model revealed that the reactions followed a pseudo-first order kinetic model.