One-pot Three-component Condensation Reaction Research Articles

Synthesis of Tryptamine-Thiazolidin-4-one Derivatives and the Combined In Silico and In Vitro Evaluation of their Biological Activity and Cytotoxicity.

Tryptamine, a monoamine alkaloid with an indole ring structure, is derived from the decarboxylation of the amino acid tryptophan, which is present in fungi, plants, and animals. Tryptamine analogues hold significant therapeutic potential due to their broad pharmacological activities, including roles as neurotransmitters and potential therapeutic agents for various diseases. Structural modifications of tryptamine enhance receptor selectivity and metabolic stability, improving therapeutic efficacy. These modifications are crucial for optimizing pharmacokinetic and pharmacodynamic properties, making the analogues more effective and safer for clinical use. In this study, novel tryptamine-thiazolidin-4-one (YS1-12) derivatives were synthesized via a one-pot three-component condensation reaction. The synthesized compounds are characterized by different spectroscopy techniques such as FT-IR, 1H NMR, 13C NMR, and HR-NMS. The synthesized compounds were subjected to binary QSAR disease models for bioactivity prediction and a target prediction model for target analysis. Potential targets were identified, and physics-based molecular simulations were conducted. Additionally, MM/GBSA binding free energy analysis was performed to calculate the average binding free energies of YS1-12 compared to reference molecules. Our computational results indicated promising biological activities for these new compounds. To further investigate these activities, the compounds were tested in vitro using two different cancer cell lines: YKG-1 glioblastoma and SH-SY5Y neuroblastoma cells. The results confirmed the potential activities of these novel compounds. Notably, compounds YS4 and YS10 exhibited favorable activities compared to the control compounds 5-FU and Temozolomide. YS4 demonstrated an IC50 value of 20 nM against YKG-1 cells, while YS10 exhibited an IC50 value of 0.44 nM against SH-SY5Y cells.

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.

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.

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.

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.

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.

Bir Etkili Tek Ortamda Üç Bileşenli Yeni Kinazolin-4-Karboksilik Asit ve Onun Ester ve Amit Türevlerinin Sentezi

A series of novel quinazoline derivatives, which may be drug candidates, were synthesized, and their structures were characterized by IR, 1H NMR, 13C NMR and Q-TOF LC/MS spectrometry. First, 2-(4-chloro-phenyl)-quinazoline-4-carboxylic acid (2) was synthesized from a one-pot three-component condensation reaction of (2-amino-phenyl)-oxo-acetic acid sodium salt obtained from alkaline hydrolysis of isatin (indole-2,3-dione) with 4-chlorobenzaldehyde and ammonium acetate. The carboxylic acid compound 2 allowed the synthesis of the ester, acid chloride and amide derivatives. New quinazoline ester derivatives (3-6, 8) were synthesized by the reactions of compound 2 and various alcohols. Quinazoline amide derivatives (9-13) were then obtained from the reaction of different aliphatic and aromatic amines and 2-(4-chloro-phenyl)-quinazoline-4-carbonyl chloride (7) formed from the reaction of SOCl2 and compound 2.

Superparamagnetic Poly(aniline-co-m-phenylenediamine)@Fe3O4 Nanocomposite as an Efficient Heterogeneous Catalyst for the Synthesis of 1H-pyrazolo[1,2-a]pyridazine-5,8-diones & 1H-pyrazolo[1,2-b]phthalazine-5, 10-diones Derivatives.

The use of polymer-based catalysts has increased because of their high potential application as an effective catalyst in organic reactions. They have benefits such as high efficiency and reactivity, simple separation, and safety compared to other heterogeneous catalysts. The objective of the current research is to prepare solid polymer-based catalysts, poly(aniline-co-m-phenylenediamine) (PAmPDA), and its superparamagnetic nanocomposite. Then, the catalytic activity of the resulting superparamagnetic nanocomposite was investigated in the synthesis of 1H-pyrazolo[1,2-b]phetalazine-5,10-diones and 1H-pyrazolo[1,2-a]pyridazine-5,8-dione derivatives. A series of some 1H-pyrazolo[1,2-b]phetalazine-5,10-diones and 1H-pyrazolo[1,2-a]pyridazine-5,8-dione derivatives was tested for its antibacterial properties against the Staphylococcus aureus and E. coli bacteria. PAmPDA copolymer was synthesized in a 1:2 molar ratio of Ani to mPDA via radical oxidative polymerization at room temperature. Superparamagnetic PAmPDA@Fe3O4nanocompo-site was synthesized from a mixture of Fe(II), Fe(III) solution, and PAmPDA copolymer via the in-situ co-precipitation technique. 1H-pyrazolo[1,2-b]phetalazine-5,10-diones were synthesized via one-pot three-component condensation reaction of Phthalhydrazide, aromatic aldehyde derivatives, and malono-nitrile in the presence of PAmPDA under solvent-free conditions at 80 °C. The synthesis of 1H-pyrazolo[1,2-a]pyridazine-5,8-dione derivatives was carried out via a one-pot three-component condensa-tion reaction of maleic hydrazide, aromatic aldehyde derivatives, and malononitrile in the presence of PAmPDA under reflux conditions at EtOH/H2O 1:1. The antibacterial activity of some derivatives was tested against Gram-positive and Gram-negative bacteria. First, superparamagnetic PAmPDA@Fe3O4 nanocomposite was synthesized and characterized successfully, and then the resulting nanocatalyst was used for the synthesis of pyrazolo[1,2-b]phthalazine and pyrazolo[1,2-a]pyridazine. We obtained the maximum yield of the desired 1H-pyrazolo[1,2-b]phthalazine-5,10 dione derivatives with 0.05 g of catalyst at 80°C, under solvent free conditions, whereby the reaction was complete within 30 min. A wide range of 1H-pyrazolo[1,2-b]phthalazine-5,10 dione derivatives were synthesized in good to excellent yield. On the other hand, pyrazolo[1,2-a]pyridazine derivative was synthesized successfully in high yield using PAmPDA as a nanocatalyst. The antibacterial activity of some derivatives, according to the data (inhibition zone%), showed good ac-tivity against Staphylococcus aureus and E. coli. In this research, PAmPDA was used for mild preparation of 1H-pyrazolo [1,2-a]pyridazine-5,8-diones & 1H-pyrazolo[1,2-b]phetalazine-5,10-diones derivatives with excellent yields and short reac-tion times. The attractive features of this protocol are simple procedure, cleaner reaction, and the use of recyclable nanocatalyst. Satisfactory yields of products and easy workup make this a useful protocol for the green synthesis of this class of compounds. The antibacterial activity of some derivatives, according to the data (inhibition zone%), showed good activity against Staphylococcus aureus and E. coli.

One-pot three-component synthesis of thioether linked 4-hydroxycoumarin-benzothiazole derivatives under ambient condition and evaluation of their biological activity

An efficient and convenient method has been outlined for the synthesis of 3-[(1,3-benzothiazol-2-ylsulfanyl)(phenyl)methyl]-2H-chromen-4-ol derivatives via a one-pot three-component Knoevenagel condensation reaction between 4-hydroxycoumarin, substituted aldehyde, and 2-mercapto benzothiazole in the presence of 10 mol% L-proline as an efficient catalyst in ethanol. The structure of all the newly synthesized chromone derivatives was confirmed by different spectroscopic techniques like IR, 1H NMR, 13C NMR, and LC-MS. Further, all the derivatives were screened for their biological activities such as anti-mycobacterial activity, in vitro antioxidant activity, anticancer activity, and molecular docking studies.

Graphene-oxide/schiff base N2O4 ligand-palladium: A new catalyst for the synthesis of furan derivatives

In this paper, we aimed at synthesizing GO/H2L-Pd nano-composites (graphene-oxide/schiff base N2O4 Ligand-palladium) as a new heterogeneous catalyst. Different analytical techniques were applied in order to analyze the chemical composition and the structure of the catalyst. The findings revealed that GO/H2L-Pd could catalyze synthesis of furan derivatives in one-pot three-component condensation reaction by different aromatic aldehydes, arylamine and acetylenedicarboxylate. The major advantages of this study are the green and mild procedure, easy reaction work-up, short reaction time, high yields, and reusability of the catalyst.

Preparation and Characterization of Novel Nano-cellulose-OSO3H Prepared from the Almond Shell as a Catalyst and Its Application in Synthesis of 2-Amino-3-Phenylsulfonyl-4-Aryl-4H-Benzo[h]Chromen Derivatives

The novel nano-cellulose-OSO3H prepared from the almond shell was synthesized via preparing mesoporous almond shell as an efficient support followed by treatment with chlorosulfonic acid (ClSO3H). This catalyst was characterized by FT-IR, FE-SEM, TEM, EDX, BET, TGA and XRD methods. Through SEM device, the size of the cellulose-OSO3H nanocatalyst revealed <30 nm. The catalytic activity of the solid acid catalyst has been successfully investigated in a one-pot three-component condensation reaction. In these procedures, aromatic aldehydes, α-naphthol and (phenylsulfonyl)acetonitrile were applied under solvent-free condition producing 2-amino-3-phenylsulfonyl-4-aryl-4H-benzo[h]chromen derivatives with high yields.

A New Supported Manganese-Based Coordination Complex as a Nano-Catalyst for the Synthesis of Indazolophthalazinetriones and Investigation of Its Antibacterial Activity

A new magnetic supported manganese-based coordination complex (Fe3O4@SiO2@CPTMS@MBOL@ Mn) was prepared in consecutive stages and characterized via various techniques (VSM, SEM, TEM, XRD, FT-IR, EDX, TG-DTA, and ICP). To evaluate its application, it was used for synthesis of divers Indazolophthalazinetriones in a simple procedure via the one-pot three-component condensation reaction of aldehydes, dimedone, and phthalhydrazide in ethanol under reflux conditions. The Mn catalyst can be recycled without any noticeable loss in catalytic activity. Additionally, the antibacterial properties of the nano-catalyst were studied against some bacterial strains.

An efficient synthesis of novel spiro[indole-3,8′-pyrano[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidine derivatives via organobase-catalyzed three-component reaction of malononitrile, isatin and heterocyclic-1,3-diones

In this research, firstly, some derivatives of sulfur containing [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one have been synthesized and then they were used for the synthesis of novel derivatives of 6′-amino-2,9′-dioxo-2′-phenyl-9′H-spiro[indoline-3,8′-pyrano[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidine]-7′-carbonitriles via a one-pot three-component condensation reaction of 7-hydroxy-2-phenyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives, malononitrile and isatin compounds in the presence of DABCO as a organocatalyst and under solvent-free conditions. In this report, a new family of spiro-pyrano-thiadiazolo-pyrimidine derivatives have been synthesized in short reaction times (10–60 min) and good to excellent yields (80–96%). The structures of all synthesized products have been confirmed by IR, 1H NMR, 13C NMR and mass spectrometry, and the structure of one selected product was characterized by single-crystal X-ray diffraction studies as well.

Organobase-catalyzed one-pot three-component synthesis of novel pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine derivatives

An efficient, simple and fast procedure has been developed for the synthesis of a novel types of pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine derivatives through the one-pot three-component condensation reaction of 7-hydroxy-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-5-one, malononitrile and aromatic aldehydes in the presence DIPEA (N,N-diisopropylethylamine) as an available organo-base catalyst. This proposed procedure leads to the synthesis of desired products in short reaction times (5–10 min) and excellent isolated yields (90–94%).

Efficient One-Pot Synthesis of 1,4-Dihydropyridine and Polyhydroquinoline Derivatives Using Sulfanilic Acid-Functionalized Boehmite Nano-Particles as an Organic-Inorganic Hybrid Catalyst

Boehmite nanoparticles (BNPs) with a wide surface area and a large number of surface hydroxyl groups were covalently functionalized by 3-chloropropyl trimethoxysilane to support sulfanilic acid. This is a hybrid catalyst was then characterized by Fourier transform infrared spectroscopy, field emission scanning electron microscopy (FESEM), thermal gravimetric analysis, X-ray diffraction and energy-dispersive X-ray spectroscopy. Accordingly BNPs@Si(CH2)3@NHSO3H was used as an effective catalyst for the one-pot three-component Hantzsch condensation reaction of aryl aldehydes, ammonium acetate and ethylacetoacetate for synthesize polyhydroquinolines and 1,4-dihydropyridine derivatives. These reactions were carried out in ethanol solvent under reflux conditions. This way offered here is operationally easy, environmentally benign, straightforward work-up, short reaction time and has high yield. Further, the heterogeneous catalyst be recycle simply and reused.

Retracted Article: Boric acid in magnetized water: clean and powerful media for synthesis of 3,4-dihydropyrimidin-2(1H)-ones.

Water was magnetized via an external magnetic field and employed, for the first time, as a solvent in green preparation of 3,4-dihydropyrimidin-2(1H)-ones by the one-pot three-component condensation reaction using boric acid as a catalyst. Shorter reaction times, higher yields, and cleaner reaction profiles were some advantages of using magnetic water.

Cellulose-Supported Sulfonated Magnetic Nanoparticles: Utilized for One-pot Synthesis of α-Iminonitrile Derivatives.

Through this method, a one-pot three-component condensation reaction of various aldehydes, primary amines and trimethylsilylcyanide (TMSCN) were applied to synthesize the desired products. It was performed in absolute ethanol and under a mild condition by using the presented nanocatalyst. High reaction yields were obtained through using the presented magnetic agent, as well. Moreover, the threecomponent reactions were executed using accessible and economical precursors. The convenient separation and recyclability of the used nanocatalyst were also precisely investigated. In this research, we identified novel α-iminonitrile derivatives using 1H NMR, 13C NMR, CHN, and FT-IR analyses, as well. In order to determine the well-known derivatives, we used FT-IR method as well as comparing their melting points with those of reported. In summary, an extremely efficient method was used for the environmentally-friendly synthesis of α-iminonitrile derivatives that are important bioactive substances. The catalytic oxidative coupling reaction afforded the products via a one-pot three-component condensation reaction of various aldehydes, primary amines and TMSCN with great reaction yields, in ethanol under mild conditions.

Development of novel and green NiFe2O4/geopolymer nanocatalyst based on bentonite for synthesis of imidazole heterocycles by ultrasonic irradiations

Geopolymers as aluminosilicate inorganic polymers and eco-friendly building materials which can be used as substrate for different kinds of composite. In this research, according to the fabrication of geopolymer based on bentonite as a substrate and embedment of NiFe2O4 nanoparticles in the construction of this polymer, the synthesis of a new magnetic nanocomposite (NiFe2O4/geopolymer) was investigated for the first time. In order to describe its chemistry and morphology features, different analyses such as Fourier transform infrared spectroscopy, field-emission scanning electron microscopy and transmission electron microscopy images, Brunauer–Emmet–Teller adsorption–desorption isotherm, X-ray diffraction pattern, energy-dispersive X-ray analysis, thermogravimetric analysis, and vibrating-sample magnetometer analysis were used. The application of this novel nanocatalyst was studied for one-pot three-component condensation reaction of substituted imidazole derivatives by accelerated ultrasonic irradiations. Compared to the other conventional catalysts which were used for the synthesis of imidazole derivatives, the green synthesis method for fabrication of this heterogeneous and magnetic nanocatalyst, its high thermal stability, being eco-friendly, noticeable efficiency and easy reusability have become privileges to be superior.

Synthesis and Structure-Activity Relationship of C-Phenyl D-Glucitol (TP0454614) Derivatives as Selective Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitors.

Sodium-glucose cotransporter 1 (SGLT1) is the primary transporter for glucose absorption from the gastrointestinal tract. While C-phenyl D-glucitol derivative SGL5213 has been reported to be a potent intestinal SGLT1 inhibitor for use in the treatment of type 2 diabetes, no SGLT1 selectivity was found in vitro (IC50 29 nM for hSGLT1 and 20 nM for hSGLT2). In this study we found a new method of synthesizing key intermediates 12 by a one-pot three-component condensation reaction and discovered C-phenyl D-glucitol 41j (TP0454614), which has >40-fold SGLT1 selectivity in vitro (IC50 26 nM for hSGLT1 and 1101 nM for hSGLT2). The results of our study have provided new insights into the structure-activity relationships (SARs) of the SGLT1 selectivity of C-glucitol derivatives.