One-pot Multicomponent Reaction Research Articles

Enhanced Catalytic Activity of Binuclear Oxidovanadium(IV) Bisbenzimidazole Linked Porphyrin Dimer for the Generation of Biologically Active 3,4-Dihydropyrimidinones and Their Corresponding Thiones.

Binuclear vanadyl(IV) porphyrin (V2BP), where two vanadium(IV) porphyrin macrocycles are linked through benzimidazole units at the β-positions, has been prepared and characterized with various techniques, such as UV-vis, Fourier transform-infrared, electron paramagnetic resonance, cyclic voltammetry, density functional transform calculations, and mass spectrometry. V2BP exhibits a red shift (Δλmax = 10 nm) in the Soret band as compared with unsubstituted parent vanadyl(IV) meso-tetraphenylporphyrin (VP). The synthesized binuclear vanadyl(IV) porphyrin (V2BP) has further been studied as a catalyst to explore a single-pot multicomponent Biginelli reaction producing biologically active 3,4-dihydropyrimidin-2-(1H)-one (DHPM)-based biomolecules and the corresponding thiones under solvent-free conditions and its catalytic activity has been compared with vanadyl(IV) meso-tetraphenylporphyrin (VP). Several reaction conditions, such as the amount of catalyst, time, solvent, and temperature, have been optimized to obtain the maximum yield of DHPMs or thiones. The synthesized β-functionalized V2BP porphyrin dimer manifests much higher conversion (84-95% yield) of DHPMs or the corresponding thiones under the optimized reaction conditions with high TON (4454-5037) and TOF (1113-1259 h-1) values for the one-pot multicomponent Biginelli reaction as compared to the literature. The catalyst exhibited excellent recyclability up to 10 cycles.

Green and Convenient Synthesis of Pharmaceutically Active Mono and Bis-dihydroquinazolines via a One-pot Multicomponent Reaction Under Sulfamic Acid Catalysis

Introduction: Multicomponent reactions (MCRs) and green chemistry are essential criteria for the development of efficient chemical syntheses for valuable organic compounds. Method: The design, synthesis, and development of sustainable procedures for the production of novel biological and pharmaceutical molecules have gained high importance. Herein, an environmentally benign synthesis of mono- and bis-2,3-dihydroquinazolin-4(1H)-ones as pharmaceutically active compounds was carried out in good to high yields of 80-99% within 45-120 minutes. Result: The desired products were synthesized via three-component and pseudo five-component condensations of isatoic anhydride, a primary amine (aniline or ammonium acetate), and an aldehyde/dialdehyde using sulfamic acid (20%) as a solid acidic catalyst under the solvent-free condition at 100°C. Conclusion: The easy work-up procedure, metal-free and environmentally benign catalyst, green reaction conditions for performing MCRs, and high yields of pure products are some advantages of the presented protocol.

Synthesis of Polysubstituted Pyridines via Nitrogen-doped Graphene Catalyzed One-Pot Multicomponent Reaction under Solvent-Free Conditions

Abstract: Polysubstituted pyridine derivatives were produced with high to excellent yields in the presence of nitrogen-doped graphene (NDG) as a dual acid-based catalyst. NDG efficiently catalyzes the multicomponent reaction between arylaldehydes, diethyl-acetylene dicarboxylates, malononitrile, and ammonium acetate under solvent-free conditions at 80°C to afford the polysubstituted pyridines in short reaction times. The structures of the synthesized pyridines were established by Ft-IR, 1H, and 13C NMR spectroscopic analysis. The advantages of this method include the in-situ oxidation of prepared 1,4-dihydropyridines, one-pot procedure, solventless system, operational simplicity, and no column chromatography. Additionally, neither toxic solvents nor catalysts are needed, and the procedure can be very reliable among the reported methodologies. The yields and reaction times in the presence of four times recycled catalyst are in comparable to the fresh catalyst.

Synthesis and biological evaluation of new 2-Amino-7-hydroxy-8-methyl-4-aryl-4H-chromene-3-carbonitrile derivatives

A series of new 2-amino-7-hydroxy-8-methyl-4-aryl-4H-chromene-3-carbonitrile derivatives (4a-4g) have been synthesized by a one-pot multicomponent reaction of 2-methylresorcinol (1) and malononitrile (2) with various aldehydes (3). All the synthesised compounds (4a-4g) have been characterised using FT-IR, 1H NMR, 13C NMR, HR-MS and evaluated for swarming behaviour, biofilm formation, biofilm disruption and urease activity against P. mirabilis (MTCC-425). Among all the synthesized compounds, compounds 4a, 4b and 4g showed slightly inhibited swarming behaviour and compounds 4f and 4g inhibited biofilm formation with increasing concentration. SEM (Scanning Electron Microscope) imaging shows that compound 4e effectively disrupts the preformed biofilm. Also, compounds 4d and 4e showed 40% reduction in urease activity. The SAR studies of synthesized compounds are elaborated in detail to provide key structural features. Furthermore, molecular docking studies against urease could provide a mechanistic basis for the inhibition. The per-residue interaction analysis suggested the involvement of non-bonded and bonded interactions with the active site of urease. Hence, the aim of the below study was to synthesize new chromene derivatives and study their biological activities.

Organoselenium-Catalyzed C2,3-Diarylation of N-H Indoles.

An organoselenium-catalyzed C2,3-diarylation of unprotected N-H indoles with electron-rich aromatics has been developed. This one-pot multicomponent tandem cross-dehydrogenation coupling reaction allows for the incorporation of two different aromatic groups to indoles. More importantly, this approach offers significant advantages, including a high atom and step economy, eliminating the need for prepreparation of the reaction substrates, streamlining the synthetic process and enhancing its practicality. Overall, this organoselenium-catalyzed C2,3-diarylation reaction presents an efficient and versatile strategy for the functionalization of indole derivatives.

One-pot multicomponent reaction: An efficient synthesis of 4-(HET)Aryl-substituted pyrazolo-quinolinones.

Pyrazolo-quinolinones (PQs) are a versatile class of Organic chemistry and it was found that they have very advanced functionally promising as selective compounds due to their scaffold and demonstrated low toxicity and considerable clinical promise. Moreover, these compounds have an important role in different applications such as analytical reagents, technical, pharmaceutical development, and biological markers. So, we aimed to synthesize and characterize new 4-(Het)aryl-substituted Pyrazole-quinolinones. Synthesis of One-Pot Multicomponent Reaction was carried out with the reaction of 5-amino-3-methyl-1H-pyrazole 1a, and 5-amino-3-phenyl-1H-pyrazole 1b and dimedone 2 with some (het)aryl aldehydes 3 using ethanol. Characterizations such as the linear structures and the regiospecificity of the reactions were determined by using NMR, GC-MS, IR, and UV measurements. This research will be very useful for all methods and procedures using multi-one-point reactions which are very popular in the synthesis of heterocyclic systems for pyrazole- quinoline skeleton synthesis.

TCS/ZnCl2 as a controlled reagent for the Michael addition and heterocyclic cyclization based on the phenyl pyrazolone scaffold with docking validation as a Covid-19 protease inhibitor

TCS/ZnCl2 is presented as a new catalyst for achieving the Michael addition adduct 5a-g by the reaction of phenyl pyrazolone 4 as the Michael donor and arylidene derivatives 3a-g as the Michael acceptor. The one-pot multi-component reaction of the same fragments' scaffolds as aldehydes 1a-g, malononitrile (2), and phenyl pyrazolone 4 with the same catalyst gives pyrano[2,3-c]pyrazole derivatives 6a-g as final products. The prepared compounds undergo docking validation as COVID-19 protease inhibitors and are compared with hydroxychloroquine as a reference drug. KEY WORDS: Pyranopyrazole, multi-component reactions, TCS/ZnCl2 catalyst, COVID-19, the energy score, hydroxychloroquine Bull. Chem. Soc. Ethiop. 2024, 38(4), 1119-1127. DOI: https://dx.doi.org/10.4314/bcse.v38i4.24

A efficient, regioselective and solvent free synthesis of 5,9-dihydropyrimido[4,5-e][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-diones derivatives in presence nanocatalyst sulfuric acid grafted with silica-3-aminotriazol

In this research, SO3H-functionalized Silica grafted 3-amino triazol has been prepared and identified through FT-IR, XRD, EDX, Fe-SEM, and TGA spectra. 3-chloropropyltriethoxysilane was first reacted with silica nanoparticles and then treated with 3-amino-1H-1,2,4-triazoles and grafted finally with chlorosulfonic acid to prepare SiO2@(CH2)3-AT/SO3H (SNPS-AT/SO3H). Afterward, the catalytic efficiency has been investigated as a homogeneous and recyclable catalyst for the solvent-free synthesis of 5,9-dihydropyrimido[4,5-e][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-diones by the one-pot multi-component reaction of aromatic aldehydes with 3-amino-1H-1,2,4-triazoles and 1,3-dimethyl barbituric acid under thermal (100 °C) conditions.

CuPd bimetallic nanoparticles supported magnetic ionic liquid-derived N-doped carbon as a highly efficient heterogeneous catalyst for the one-pot oxidative multicomponent reactions

BackgroundMulticomponent reactions often rely on aldehydes as the reactants, limiting their widespread use. To enhance the versatility and scope of these reactions, aldehydes can be replaced with alcohols. MethodsIn this study, nitrogen-doped magnetic carbon nanostructures modified with imidazolium-based ionic liquid (Fe3O4@NC-IL) were prepared. These nanostructures were synthesized by a one-pot hydrothermal carbonization method using ferric chloride in the presence of glucose, urea, epichlorohydrin and 1-methylimidazole as carbon source, nitrogen source, linker and ionic liquid, respectively. Then, CuPd bimetallic nanoparticles were immobilized on the synthesized nanostructures by a wet chemical reduction process. Significant findingsThe catalytic activity of the nanostructures was evaluated in the oxidation of alcohol under base-free conditions. The results indicate that the CuPd bimetallic catalyst exhibited better catalytic performance than both Cu and Pd monometallic catalysts, suggesting a synergistic effect between copper and palladium. Also, a non-ionic liquid-based catalyst was synthesized and used in the model reaction to study the effect of imidazolium ionic liquid species on the catalytic activity. The results showed that these species enhanced the catalytic activity. Finally, the catalytic activity of the synthesized structure was evaluated through a one-pot tandem oxidative synthesis of dihydropyrimidinones (Biginelli reaction) and dihydropyridines (Hantzsch reaction).

Polymer Supported Nitrogen-Bridged Symmetrical Binuclear Dioxidomolybdenum(VI) Complexes and Their Homogeneous Analogues as Potential Catalysts for Efficient Synthesis of 2-Amino-3-Cyano-4H-Chromenes/Pyrans.

Reaction of 2-chloromethyl-1H-benzimidazole with known intermediates (i-iii), prepared from diaminoguanidine hydrochloride with salicylaldehyde, 5-bromosalicylaldehyde or 3,5-di-tert-butylsalicylaldehyde, in the presence of triethylamine (NEt3) led to the formation of benzimidazole appended new ligands, H4L1-H4L3 (I-III). The homogeneous nitrogen-bridged symmetrical binuclear complexes, [(MoVIO2)2(L1)(H2O)2] (1), [(MoVIO2)2(L2)(H2O)2] (2) and [(MoVIO2)2(L3)(MeOH)2] (3) have been isolated by reacting these ligands with [MoVIO2(acac)2] in a 1 : 2 molar ratio in refluxing methanol. Using 1 : 1 (ligand to Mo precursor) molar ratio under above reaction conditions resulted in the corresponding mononuclear complexes, [MoVIO2(H2L1)(MeOH)] (4), [MoVIO2(H2L2)(H2O)] (5) and [MoVIO2(H2L3)(MeOH)] (6). The binuclear heterogeneous compounds [(MoVIO2)2(L1)(DMF)2]@PS (PS-1), [(MoVIO2)2(L2)(DMF)2]@PS (PS-2) and [(MoVIO2)2(L3)(DMF)2]@PS (PS-3) have been obtained by immobilization of 1-3 onto chloromethylated polystyrene (PS) beads. All synthesized ligands, homogeneous as well as supported compounds have been characterized by elemental analyses and various spectroscopic methods. Single crystal X-ray diffraction study of complexes 1 and 3 confirms their nitrogen-bridged symmetrical binuclear structures while 4 is mononuclear. Heterogeneous compounds (PS-1-PS-3) have further been studied by microwave plasma atomic emission spectroscopy, X-ray photoelectron spectroscopy, and field emission scanning electron microscopy along with energy dispersive spectroscopy. These compounds (homogeneous and heterogeneous) were explored for catalytic applications to one-pot multicomponent reactions (MCRs) for efficient synthesis of biologically active 2-amino-3-cyano-4H-chromenes/pyrans (21 examples). Optimising various reaction parameters helped in achieving as high as 97 % yields of products. Though, only half equivalent of the binuclear complexes (1-3) was required compared to mononuclear analogues (4-6) to achieve comparable yields, heterogeneous catalysts have an added advantage due to their stability and recyclability. Suitable reaction mechanism has also been proposed based on isolated intermediates.

Novel pyridine bearing pentose moiety-based anticancer agents: design, synthesis, radioiodination and bioassessments

Pyridine compounds are one of the most important heterocyclic derivatives showing wide ranges in biological and pharmacological activities. Green chemistry eliminates or reduces the generation of hazardous compounds. It prevents pollution at a molecular level. The microwave technique used in heterocyclic compound synthesis is also an important branch of green chemistry techniques. In this study, we report designing and synthesizing a new pyridine-bearing pentose moiety via a one-pot multicomponent reaction using D-glucose and also investigate its behavior and reactivity toward some simple and heterocyclic amino derivatives. The chemical structures of the synthesized compounds were characterized and tested for their cytotoxic activities. Some of the test compounds exhibited slight to high cytotoxic activities against Caco2 (colon cancer) cells, HepG2 (hepatocellular carcinoma) cells and MCF-7 (human breast cancer) cells by MTT assay. The results showed clearly that compound 4 and compound 8 displayed strongest to moderate cytotoxic activity against the HepG2, Caco2 and MCF-7 respectively and compound 1 showed good activity against MCF-7 in comparison to the standard anticancer drug doxorubicin. These data were by cytopathological examination. An in-vivo radioactive tracing study of compound 4 proved its targeting ability to sarcoma cells in a tumor-bearing mice model. Our findings suggest that the synthesized compounds may be promising candidates as novel anticancer agents.

A Review on the Recent Multicomponent Synthesis of 4H-Pyran Derivatives

Abstract: 4H-Pyran is a well-known moiety, which appears in various natural and synthetic products. These compounds include various biological activities like anti-hepatotoxic, antitumor, anti-inflammatory, antioxidant, anti-spasmolytic, diuretic, estrogenic, anticoagulant, antifungal, antiviral, anti-helminthic, antimicrobial, hypothermal, anti-tubercular, anti-HIV, herbicidal, anticonvulsant and analgesic activity. This review has summarized an overview of general strategies that allow the design of 4H-pyran derivatives via catalyzed one-pot multicomponent reactions.

Reaction Optimization of Strontium Perchlorate Catalyzed Novel Protocol for Stereoselective Synthesis of Dihydropyrimidinones.

Hydrated strontium perchlorate [Sr(ClO4)2.3H2O] acts as a very strong oxidizing and dehydrating agent. Until now, it could not be reported as a catalyst in dehydration mechanism-based organic synthetic reactions. Therefore, it is important to find whether it could be an effective catalyst for one-pot multicomponent reactions (MCRs). The main objective of the present work is the development of a novel process for the synthesis of 1,4-dihydropyrimidinones through the one-pot multicomponent strategy using hydrated Sr(ClO4)2 as a catalyst. Furthermore, it includes process optimization, stereoselectivity, and spectroscopic characterization of the synthesized compounds. Conventional and microwave-supported synthesis of 1,4-dihydropyrimidinones using 20 mol % of hydrated Sr(ClO4)2 catalyst via the one-pot solvent-free reaction was discovered as a new catalytic MCR methodology. The box-Behnken design approach and advanced analytical techniques were used for process optimization and reaction analysis. The results confirmed that hydrated Sr(ClO4)2; works as an efficient catalyst for one-pot multicomponent organic synthesis under both conventional and microwave heating. It is an effective catalyst for laboratory synthesis of 1,4-dihydropyrimidinones stereoselectively with moderate to excellent yield without any undesirable effect. Microwave heating provided the desired product within 1-4 minutes. Moreover, this method provides easy isolation of the pure products simply by recrystallization, and without the use of a chromatographic purification method. The simplicity and neutrality of reaction conditions, easy post-reaction workup, higher satisfactory to excellent yield, effectiveness, the diversity of substrates, etc. render the hydrated Sr(ClO4)2 catalyst-based protocol for the stereoselective synthesis of 1,4-dihydropyrimidinones as a highly efficient method. Furthermore, it has been found to be safe un-der laboratory reaction conditions and no undesirable issues have been faced during the process.

Novel terpyridines as Staphylococcusaureus gyrase inhibitors: efficientsynthesis and antibacterialassessment viasolvent-drop grinding.

Aim: This study was designed to synthesize a novel series of terpyridines with potential antibacterial properties, targeting multidrug resistance. Materials & methods: Terpyridines (4a-h and 6a-c) were synthesized via a one-pot multicomponent reaction using 2,6-diacetylpyridines, benzaldehyde derivativesand malononitrile or ethyl 2-cyanoacetate. The reactions, conducted under grinding conditions with glacial acetic acid, produced high-yield compounds, confirmed by spectroscopic data. Results: The synthesized terpyridines exhibited potent antibacterial activity. Notably, compounds 4d and 4h demonstrated significant inhibition zones against Staphylococcusaureus and Bacillussubtilis, outperformingciprofloxacin. Conclusion: Molecular docking studies highlighted compounds 4d, 4hand 6c as having strong binding affinity to DNA gyrase B, correlating with their robust antibacterial activity, suggesting their potential as effective agents against multidrug-resistant bacterial strains.

Controlled generation of ortho-quinone methides and (4+3) cyclization with 2-indolylalcohols by dual photoredox/Brønsted acid relay catalysis

Given the significance of oxacyclic frameworks in molecular scaffolds and drug discovery, it is intriguing to precisely construct and manipulate such ring systems in chemical research. In this area, the intermolecular, multicomponent cyclization for the synthesis of diversely substituted seven-membered ring oxacycles under simple conditions is still a challenge. Here, we report a dual photoredox/Brønsted acid relay catalytic strategy for in situ generation of ortho-quinone methides and subsequent (4 ​+ ​3) cyclization with 2-indolylalcohols. In this one-pot multicomponent reaction, two C–C and one C–O bonds are formed, providing de novo access to various biologically important indole-fused, oxygen-containing seven-membered heterocycles. By virtue of a chiral phosphoric acid, an asymmetric version can also be achieved with good to excellent levels of enantioselectivity (up to 96:4 er).

Fabrication and characterization of inorganic-organic hybrid copper ferrite anchored on chitosan Schiff base as a reusable green catalyst for the synthesis of indeno[1,2-b]indolone derivatives.

This study presents a description of the catalytic synthesis of indeno[1,2-b]indolone derivatives. In this method, initially, a Schiff base compound was synthesized from the reaction of acetylacetone with 2-hydroxyaniline. Then, the prepared Schiff base was immobilized on chelated magnetic copper ferrite nanoparticles with a chitosan surface to design and prepare the CuFe2O4@CS-SB nanocomposite. Further, the one-pot multi-component cyclization reaction of aniline, dimedone and ninhydrin was conducted using the synthesized nanocomposite as a heterogeneous acid catalyst in water solvent under thermal conditions. In this reaction, the products were obtained in excellent yields and short reaction times, and the catalyst could be recycled and reused six times without any loss in product yields. By conducting FT-IR spectroscopy, 1H NMR spectroscopy, XRD, FE-SEM, TGA, elemental mapping scanning, EDX and BET analyses, the structure of the nanocatalyst was characterized. In addition, for the identification of organic compounds, FT-IR, 1H NMR, and 13C NMR spectroscopies and melting point analysis were used, which confirmed the synthesis of this class of derivatives.

Facile synthesis of tetrahydroquinoline containing dithiocarbamate derivatives via one-pot sequential multicomponent reaction.

An efficient sequential multi-component method for the synthesis of tetrahydroquinoline containing dithiocarbamates has been developed. This reaction involved a boronic acid-catalysed reduction of quinolines to tertrahydroquinolines, followed by nucleophilic addition reaction with carbon disulphide to form dithiocarbamic acids and subsequent S-arylation via external base-free Chan-Evans-Lam coupling in a one-pot operation. The methodology is compatible with a wide variety of functional groups and also useful in the late-stage functionalization of pharmaceuticals. The dual role of the boronic acid as a catalyst (in the reduction of quinolines) and as a reagent (in the S-arylation) has been demonstrated for the first time herein.

A eutectogels-catalyzed one-pot multi-component reaction: access to pyridine and chromene derivatives.

The demand for a wide array of functional chemicals and materials has experienced a significant surge in tandem with the advancement of civilization. Regrettably, a number of perilous solvents are employed in chemical laboratories and industrial settings, posing significant risks to the well-being of researchers and contributing to environmental degradation through pollution. Eutectogels, which are based on the eutectic concept, may be synthesized by self-assembling or self-polymerization of various components when put under UV irradiation (254 nm). A novel copolymeric deep eutectic solvent (DES) was successfully synthesized, comprising choline chloride (HBA) as the hydrogen bond acceptor, acetamide (HBD) as the hydrogen bond donor, tetraethyl orthosilicate (TEOS), and formic acid. In this study, we present the preparation of four-component ETGs for synthesizing pyridine and chromene derivatives as a reusable catalyst through a multi-component pathway without solvents. The procedure of synthesizing these heterocyclic compounds is free of using toxic solvents and it could be categorized as a green method.

Recent advances in the transformation reactions of the Betti base derivatives.

Betti bases are the products resulting from the one-pot multicomponent reaction involving 1-naphthol/2-naphthol, aliphatic/aromatic aldehydes, and secondary amines. This chemical process is commonly referred to as the Betti reaction. The significance of Betti bases in medicinal chemistry has grown substantially due to their diverse array of pharmacological applications. Furthermore, their synthetic utility is considerable, given their use as catalysts and ligands in asymmetric synthesis. Moreover, Mannich products, incorporating diverse functional groups such as -OH and -NH, find application in a range of organic reactions. This utilization enables the synthesis of novel C-C bond linkages and diverse heterocycles, including biologically active naphthoxazines, which hold biological applications such as antibacterial, antifungal and anticancer. The focus of this review article is on the application of aminonaphthol derivatives in transformation reactions and the synthesis of organic compounds, with particular emphasis on heterocycles.

Synthesis of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives as potential anti-diabetic and anticancer agents

In this work, we developed a series of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives 4(a-e) via a one-pot multicomponent reaction. The structures of the compounds were confirmed using analytical and spectroscopic techniques. Also, the synthesized compounds were screened for their anti-diabetic activity, cytotoxicity and in silico studies. The activity results suggested that the compound 4e exhibited least IC50 values of 0.055 ± 0.002 µM, 0.050 ± 0.002 µM and 0.009 ± 0.001 µM for α-amylase, α-glucosidase and cytotoxicity respectively. Further, in silico molecular docking results revealed that all the obtained compounds effectively interacted with exo-β-D-glucosaminidase and P38 MAP kinase proteins with good binding energies. In that, 4e compound established the least binding energy of −9.6 and −9.1 kcal/mol, respectively. Moreover, our synthesized compounds were subjected to ADME studies, which suggested that all the synthesized compounds obeyed all five rules with good bioavailability and were suitable as drug leads against anti-diabetic and anticancer treatment.