Three-component Condensation Reaction Research Articles

Synthesis and evaluation of novel sulfamethoxazole-containing 1,8-dioxo-decahydroacridine derivatives: Antimicrobial activity and emission properties

A straightforward and efficient method for synthesizing 1,8-dioxo-decahydroacridine derivatives is presented, utilizing a one-pot, three-component condensation reaction involving dimedone, sulfamethoxazole, and aromatic aldehydes. The primary objective of this synthesis is to incorporate the sulfamethoxazole ring into the acridine family structure and examine the antibacterial effects and fluorescence properties of the compounds. The antibacterial activity of the synthesized compounds was evaluated against various gram-positive and gram-negative microorganisms, as well as a fungal strain, using the disk diffusion method, minimum inhibitory concentration determination, and bactericidal assays. Notably, five compounds exhibited potent antibacterial activity against both strains of Bacillus cereus. Furthermore, the influence of pH on the fluorescence emission intensity and absorption spectrum of the synthesized compounds was investigated, revealing that all products displayed fluorescence radiation.

A Chemically Robust 2D Ni-MOF as an Efficient Heterogeneous Catalyst for One-Pot Synthesis of Therapeutic and Bioactive 2-Amino-3-Cyano-4H-Pyran Derivatives.

Despite possessing numerous catalytic advantages of MOFs, developing 2D frameworks having excellent chemical stability along with new catalytic properties, remains a grand challenge. Herein, by employing a mixed ligand synthetic approach, we have constructed a 2D Ni-MOF, IITKGP-52, which exhibits excellent framework robustness in open air, water, as well as over a wide range of pH solutions (2-12). Benefitting from its robustness and abundant Lewis acidic open metal sites, IITKGP-52 is explored in catalyzing the heterogeneous three-component condensation reaction for the tandem synthesis of bioactive 2-amino-3-cyano-4H-pyran derivatives with low catalytic loading, greater compatibility for a wide range of substrates, excellent recyclability and superior catalytic efficiency than the previously employed homo and heterogeneous systems. IITKGP-52inaugurates the employment of MOF-based catalysts for one-pot synthesis of therapeutic and bioactive 2-amino-3-cyano-4H-pyran derivatives.

Design, Green Synthesis and in silico Studies of New Substituted Naphtho[1,2-e][1,3]Oxazines as Potential Acetylcholinesterase Inhibitors.

Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory impairment resulting from the degeneration and death of brain neurons. Acetylcholinesterase (AChE) inhibitors as the primary pharmacotherapy for numerous neurodegenerative conditions, leveraging their capacity to modulate acetylcholine levels crucial for cognitive function. Recently, oxazines have brought worthy synthetic interest due to their extensive biological activities including,anti-tubercular, anti-convulsant, and anti-cancer activities. In this study, a series of novel naphtho[1,2-e][1,3]oxazine derivatives has been designed and synthesized with potential of acetylcholinesterase (AChE) inhibition. The target products have been prepared by a one-pot and three-component condensation reaction of 2-naphthol, aromatic aldehydes, and arylmethanimine in the presence of 3-methyl-1-sulfonic acid imidazolium chloride ([Msim]Cl) as an effective and recyclable catalyst under microwave irradiation solvent-free condition. The molecular docking studies has also been performed to investigate the synthetic compounds in the the AChE active site gorge. The results showed that all these derivatives interact with the enzymes with high affinity in binding pocket. The MM-GBSA studies were performed for all synthesized derivatives and among them, compound 3-(4-Chlorophenyl)-1-phenyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine 5f, showed the lowest the binding free energy (-48.04 kcal mol-1). In general, oxazine derivatives could be proposed as the strong AChE inhibitors.

One-pot Multicomponent Synthesis of Hydrazinyl Thiazoles Bearing an Isatin Moiety in Aqueous Medium

Abstract: Isatin-derivatives are an important class of nitrogen-containing heterocyclic compounds in organic synthesis. On the other hand, 1,3-thiazoles are 5-membered heterocyclic compounds containing nitrogen and sulphur atoms. Hydrazinyl thiazoles are often prepared through the classical condensation of aldehydes or ketones with thiosemicarbazide to yield thiosemicarbazones, which will then undergo heterocyclization with phenylacyl bromides to give the corresponding hydrazinyl thiazoles. Nowadays, multi-component reactions (MCRs) are considered the most powerful tool in organic synthesis. The use of water as a green solvent in organic synthesis is one of the goals of green chemistry. In this study, a series of new hydrazinyl thiazoles 3a-3u bearing an isatin moiety were synthesized in good yield via a one-pot three-component condensation reaction of isatins with thiosemicarbazide and phenyl acyl bromides in water under reflux condition. All the synthesized compounds were characterized by IR, 1D-NMR, 2D-NMR and LC/MS spectral data.

Synthesis of a Series of 4H-Pyran Derivatives with Multicomponent Reaction in DBSA/H2O Microemulsion System

A series of 4H-pyran derivatives were synthesized through a three-component condensation reaction in a pot using aromatic aldehyde, cyclohexanedione, and malononitrile in the dodecyl benzenesulfonic acid/H2O microemulsion system. This protocol is attractive because dodecyl benzenesulfonic acid microemulsion is superior for organic reaction due to its dual catalysis. On the one hand, dodecyl benzenesulfonic acid acts as a Brønsted acid to catalyze the reaction; on the other hand, it can form a microemulsion as surfactant to enlarge the boundary area and entrap water produced during esterification reaction. In addition, the reaction process is simple, with high liaison formation efficiency, good yields, and environmentally harmless reaction conditions. The dodecyl benzenesulfonic acid/H2O microemulsion system was equally effective when used in consecutive reactions.

One-Step, Low-Cost, Operator-Friendly, and Scalable Procedure to Synthetize Novel Tetrazolopyrimidinylbenzopyran-2-ones by Benign Protocol

Abstract: New coumarin chalcones 3j–p were conveniently obtained in high yields via Claisen-Schmidt condensation reaction, when acetyl coumarin 1 reacted with 3-aryl-1-phenyl pyrazole-4-carbaldehydes 2j–p in boiling ethanol in the presence of triethyl amine as a catalyst. Also, two synthetic pathways were afforded for the synthesis of novel tetrazolo[1,5-a]pyrimidinyl-2H-chromen-2-ones 5a-p. The first pathway is a multistep process including formation and separation of chalcones, which then were allowed to react with 5-aminotetrazole 4. While, the second pathway is a highly efficient one-pot three-component condensation reaction of 3-acetyl coumarin 1, aromatic aldehydes 2a-p and 5-aminotetrazole 4 under green and mild reaction conditions by using acetic acid (AcOH) as a catalyst and solvent. The molecular structure of products was established on the basis of their NMRs, IR and elemental analysis data. Solvent optimization was carried out in the reaction producing 3-(5-Phenyl-4,5-dihydrotetrazolo[1,5-a]pyrimidin-7-yl)-2H-chromen-2-one (5a). The advantages to using environmental-friendly acetic acid are simple operation, short reaction time, high efficient (97%), operationally facile and wide tolerance of starting materials. objective: The advantages of using environmental-friendly AcOH are simple operation, short reaction time, high efficient (97%), operationally facile and wide tolerance of starting materials.

Synthetic Methods of 1H-Pyrazolo[1,2-b]Phthalazine Derivatives

Abstract: This review deals with the synthetic methods of pyrazolo[1,2-b]phthalazine derivatives using one-pot multi-component reactions via modern and traditional methods. The synthetic methods are subdivided into groups according to the type of reactants e.g (1) one-pot three-component reaction of 2,3-dihydrophthalazine-1,4-dione, aldehydes and acetonitriles; (2) one-pot three-component reaction of 2,3-dihydrophthalazine-1,4-dione, aldehydes and aroyl acetonitriles; (3) one-pot three-component reaction of 2,3-dihydrophthalazine-1,4-dione, aldehydes and acetylacetone or 4-hydroxy-2H-chromen-2-one or acetylene derivatives; (4) one-pot four-component condensation reaction of phthalimide, hydrazine hydrate, aldehydes and acetonitriles; (5) one-pot four-component reaction of phthalic acid, hydrazine hydrate, indole-3- carbaldehyde and acetonitriles; and (6) one-pot three-component condensation reaction of 2,3- dihydrophthalazine-1,4-dione, aldehyde, and dimedone derivatives. Moreover, the various methods were reported.

The gentisic acid-based deep eutectic solvent mediated green synthesis of acridines

A novel gentisic acid-based deep eutectic solvent (ETPPBr/GA-DES) was prepared by mixing of ethyltriphenylphosphonium bromide (ETPPBr) and gentisic acid (GA = 2,5-dihydroxy-benzoic acid), and its structure fully investigated by using the FT-IR, TGA/DTA, densitometer and 1HNMR techniques. Different mole ration of ETPPBr to GA were examined and the eutectic point phase diagram showed that the best ratio for the synthesis of a novel gentisic acid-based DES is the one-to-one mole ratio of the two starting materials (ETPPBr and GA).Then, ETPPBr/GA-DES was used as a novel and capable catalyst for the green synthesis of diverse N-substituted decahydroacridine-1,8-diones a(1−12) from the three-component condensation reaction of aromatic aldehyde, aromatic amine and dimedone in solvent-free conditions at 80 °C.

Eco-friendly synthesis of various tri-substituted imidazole derivatives by using a novel functionalized NCP@SiO3PrNHPrSiO3TiO2 under solvent-free conditions

In this research, a novel NCP@SiO3PrNHPrSiO3TiO2 nano catalyst has been designed, synthesized and fully characterized using various analytical techniques such as; XRD, FT-IR, SEM, EDS, BET and TG analyses. The catalytic activity of NCP@SiO3PrNHPrSiO3TiO2 was also employed for the synthesis of tri-substituted imidazoles via three-component condensation reactions of aldehydes, benzyl and NH4OAc under solvent-free conditions. This synthesis features environmentally benign, short reaction time, efficiency, and feasibility of large-scale synthesis compared to classical reactions.

Novel UiO-NH2-like Zr-Based MOF (Basu-DPU) as an Excellent Catalyst for Preparation of New 6H-Chromeno[4,3-b]quinolin-6-ones.

A new two-fold interpenetrated pillar-layered metal-organic framework (MOF) was designed and synthesized based on zirconium cations, an amine-functionalized ligand, and a linear exo-bidentate bis-pyridine ligand. The structure of the prepared framework was evaluated using various techniques, such as Fourier transform infrared (FTIR), 13C NMR, energy-dispersive X-ray (EDX), elemental mapping analysis, scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis/differential thermal analysis (TGA/DTA), and Brunauer-Emmett-Teller (BET). Then, catalytic application of the prepared zirconium-based MOF was successfully explored in the synthesis of novel 6H-chromeno[4,3-b]quinolin-6-ones 4(a-l) through a one-pot three-component condensation reaction of 4-hydroxycumarine, 1-naphthylamine, and aromatic aldehydes under solvent-free conditions at 110 °C. The pure products were obtained with high atom efficiency (AE) and short reaction times and characterized by FTIR, NMR, and mass spectrometry techniques.

Lanthanum triflate as a capable catalyst for the synthesis of xanthenediones

The main purpose of this work was proposing a versatile and capable method for the synthesis of diverse xanthenediones from the three-component condensation reaction of two moles of dimedone and one mole of various aldehydes by the lanthanum triflate catalyst in solvent-free conditions at 60 °C. The products were characterized by comparison of their melting points, IR, and NMR spectra with authentic samples.

Synthesis, virtual screening, and computational approach of 6-(4-metoxyphenyl)-4-phenyl-1,2-dihydropyrimidin-2-one as a potential target for thioredoxin glutathione reductase (TGR)

The three-component condensation reaction of 4-methoxybenzaldehyde with acetophenone and urea in the presence of CF3COOH was investigated and as a result, 6-(4-methoxyphenyl)-4-phenyl-1,2-dihydropyrimidine-2-one was synthesized. The structure of the synthesized compound was confirmed by the X-ray method. Both the DFT and TD-DFT computations for comprehensive analysis of spectral data, and electronic parameters were carried out as an add-on to synthetic research and well corroborated with the experimental results. NBO, NLO, and Hirshfeld surface and energy framework analysis were also used to segregate the different intermolecular hydrogen bonds involved in the molecular packing strength. All DFT findings imply that the synthesized molecule has enhanced non-linear optical properties increased charge transfer and is a highly stable, and proactive candidate for drugs. Furthermore, molecular docking studies were carried out to investigate the binding mechanism between 6-(4-metoxyphenyl)-4-phenyl-1,2-dihydropyrimidin-2-one and the thioredoxin glutathione reductase (TGR) complex. ADMET parameter analysis was also carried out for the compound to understand the compound's safety and compound efficiency for the drug candidate.

Synthesis of 1,2,4,5-oxadiazaboroles by three-component condensations of hydroxylamines, nitriles, and diarylborinic acids

A method for the synthesis of substituted 1,2,4,5-oxadiazaboroles is described, in which hydroxylamines, nitriles, and diarylborinic acids engage in a three-component condensation reaction. The protocol provides access to a substitution pattern that is not readily available through other methods—namely, 2,3-disubstitution, with a tetracoordinate boron center. Structures of representative members of this class of heterocycles were determined by single crystal X-ray diffraction analysis.

Synthesis of new magnetic nanocatalyst Fe3O4@CPTMO-phenylalanine-Ni and its catalytic effect in the preparation of substituted pyrazoles

In this study, a new, efficient and stable magnetically heterogeneous nanocatalyst of Fe3O4@CPTMO-phenylalanine-Ni via multi steps process starting from simple and cost-effective precursors was designed and successfully synthesized, and physico-chemical, structural, and magnetic properties have fully been characterized by several analytical methods involving SEM–EDS, FT-IR, TGA, VSM, XRD, ICP, BET, TEM, and EMA. The catalytic performance of the Fe3O4@CPTMO-phenylalanine-Ni can be used as an effective and recyclable nanocatalyst with facile separation by magnetic forces for the preparation of substituted pyrazoles with high yields through the one-pot, three-component condensation reaction of various arylglyoxals, diketones, and 1H-pyrazole-5-amines under mild conditions. The nanocatalyst’s activity after being used by four consecutive times in a cycle reaction without distinct deterioration remained unchanged or was found to be a slight decrease. The advantages of this study are simplicity, low cost, facile synthesis process, and environmentally secure nature.

Catalytic application of green-synthesized ZnO nanoparticles in the synthesis of 1H-pyrazolo[1,2-a]pyridazine-5,8-diones and evaluation of their anti-cancer properties

Produced zinc oxide nanoparticles utilizing Anethum graveolens extract has used for the preparation of 1H-pyrazolo[1,2-a]pyridazine-5,8-diones under solvent-free conditions and at 70 °C through a three-component condensation reaction.

SYNTHESIS, CRYSTAL STRUCTURE, SUPRAMOLECULAR ASSEMBLY INSPECTION BY HIRSHFELD SURFACE ANALYSIS AND COMPUTATIONAL EXPLORATION OF 4-PHENYL-6-(P-TOLYL)PYRIMIDIN-2(1H)-ONE (PPTP)

The three-component condensation reaction of 4-methylbenzaldehyde with acetophenone and urea in the presence of CF3COOH was investigated and as a result, 4-Phenyl-6-(p-tolyl)pyrimidin-2(1H)-one (PPTP) was synthesized. The structure was determined by single crystal X-rays diffraction analysis which inferred that the PPTP crystallized in monoclinic crystal system with space group P21/c. The dihedral angles between the aromatic rings indicate that the molecule is non-planar. The crystal packing is mainly stabilized by N-H O and C-H O bonding which is further stabilized by off-set π π stacking interactions. The supramolecular assembly is further investigated by Hirshfeld surface analysis. The mechanical behaviour is predicted by the void analysis Moreover, the computational study is carried out for finding the interaction energy between molecular pair by using B3LYP/6-31G(d,p) electron density model. The study inferred the role of various types of interaction energies in stabilizing the crystal packing.

An Fe3O4 supported O-phenylenediamine based tetraaza Schiff base-Cu(ii) complex as a novel nanomagnetic catalytic system for synthesis of pyrano[2,3-c]pyrazoles.

In this research, we present a post-synthetic method for synthesizing a novel nanomagnetic Cu(II) Schiff base complex and investigate its efficiency in catalytic organic conversion reactions. Various spectroscopic analyses were employed to characterize the physiochemical characteristics of the resulting nanocomposite. The experimental results successfully demonstrate the catalytic application of the prepared Cu-complex in the preparation of pyrano[2,3-c]pyrazole heterocycles. This synthesis involved a one-pot three-component condensation reaction, wherein hydrazine hydrate, ethyl acetoacetate, malononitrile, and aromatic aldehydes were combined under reflux conditions using water as the solvent. Notably, the heterogenized complex exhibited exceptional catalytic performance, achieving remarkable conversion rates and selectivity, all accomplished using only 12 mg of the catalyst. Furthermore, thorough stability assessments of this catalyst were conducted through reusability and hot filtration tests, which confirmed its non-leaching properties and demonstrated excellent results over the course of five consecutive runs.

Study of Copper Based Heteropolysalts as Catalysts in the Efficiency of Synthesis of 5-Ethoxycarbonyl-4-Phenyl-6-Methyl-3,4-Dihydropyridin-2(1H)-One

The efficiency of various heteropoly compounds as well-known solid acids is investigated for the three-component condensation reaction of an aldehyde, b-ketoester and urea to afford the dihydropyrimidinones (DHPM). Compared to the classical Biginelli reaction conditions, this new method consistently has the advantage of excellent yields and short reaction time. The objective of this study is the use of Keggin heteropolyacid (HPAs) noted H3PMo12O40 and its ammonium salts H3-2xCuxPMo12O40 and (NH4)3-2xCuxPMo12O40 in Biginelli cyclocondensation reaction using: benzaldehyde, acetoacetate and urea with ratio (2:2:3) [3]. After synthesis, the prepared catalysts were characterized by: BET surface area, X- ray diffraction, Infra-red spectroscopy and DHPM by FT-IR, 1H and 13C NMR. The reaction results show that H3PMo12O40 is the best catalyst in our reaction conditions with an excellent yield around 94% which can be explained by significantly higher Brønsted acidity compared to that of traditional mineral catalysts. In the other hand, other excellent yields have been obtained in the presence of Cu0.25H2,50PMo12O40 and (NH4)3,00Cu0,00PMo12O40 89% and 59% respectively. Please use 14-point bold for your article title, with an initial capital letter for any proper nouns.

Synthesis of benzoimidazoquinazolinone and indolylxanthenone derivatives using Keggin-type heteropoly-11-molybdo-1-vanadophosphoric acid supported on Montmorillonite K-10 clay as catalyst: a green approach

Biologically as well as medicinally important two different organic scaffolds, viz. benzimidazole and quinazoline, are present in the class of heterocyclic compounds called benzimidazoquinazolinone. Similarly, indolylxanthenones are the compounds containing two important organic moieties such as indole and xanthene. In this work, a new green protocol for the synthesis of benzoimidazoquinazolinone and indolylxanthenone derivatives was attained under environmental-friendly solvent-free condition through a simple one-pot three-component condensation reaction. This condensation was achieved by using 10% heteropoly-11-molybdo-1-vanadophosphoric acid (H4[PVMo11O40])-loaded Montmorillonite K-10 clay material (PVMoK-10) as an efficient heterogeneous catalyst. The identification and characterization of the derivatives were done by physical as well as spectral techniques. Synthesis of ten derivatives of benzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one and two derivatives of 9-(1H-indol-3-yl)-2,3,4,9-tetrahydro-1H-xanthen-1-one was successfully achieved using this protocol. A tentative reaction mechanism has also been proposed for the synthetic plans.

Water mediated TBAB catalyzed synthesis of spiro-indoline-pyrano[3,2-c]quinolines as α-amylase inhibitor and in silico studies

Herein, an efficient synthesis of spiro-indoline-pyrano[3,2-c]quinolines derivatives of spiroxindolines by the water-mediated three-component condensation reaction of 2-hydroxyquinoline-4-one 1(a-b), isatin derivatives 2(a-n), and malononitrile 3 in the presence of water-soluble and phase transfer Tetrabutylammonium bromide (TBAB) catalyst is described. The present protocol shows features such as excellent yield of product, mild reaction condition, reusable reaction medium with catalyst and low E-factor. This blossomed the reaction with the green synthetic condition and provide a safe and clean alternative for the synthesis of spiropyrano[3,2-c] quinolines derivatives. All the synthesized compounds were screened against the pancreatic α-amylase. Many of those synthesized compounds possess noticeably good α-amylase inhibitory action. From the activity profile, analogous 4g and 4h were found to be more active than the others with IC50 values ranges for α-amylase inhibition (IC50 = 73.82 -76.65 µg/ml) in comparison with the standard acarbose (IC50 = 79.64 ± 0.46 µg/ml). Molecular docking results showed key interactions of 4g, 4h and acarbose with α-amylase, compound 4g shows H-bonding interaction with GLN63, HIS101 and compound 4h shows H-bonding interaction with ASP300. In silico ADMET prediction was carried out to check the physicochemical properties of the synthesized compound.