Three-component Hantzsch Research Articles

Bio-synthesized Fe(0)/Fe2O3 composite nanoparticles as a catalyst towards the preparation of dihydropyridine derivatives under solvent-free condition at room temperature

A sustainable and innovative approach has been developed for synthesizing of Fe(0)/Fe2O3 composite nanoparticles (Fe(0)/Fe2O3NPs), utilizing the bark extract of the arjun tree (Terminalia arjuna) as a reducing and capping agent. This environmentally friendly Fe(0)/Fe2O3NPs was thoroughly characterized using various analytical techniques, including UV–Visible spectroscopy, FT-IR, PXRD, HR-TEM, SEM, and XPS. The nanoparticles were then evaluated as catalysts for facilitating the three-component Hantzsch reaction with acetylacetone, ammonium acetate, and substituted aldehydes, producing bioactive dihydropyridine derivatives. The catalyst exhibited high performance over approximately five cycles, with negligible loss in yield and catalytic efficiency. Additionally, a mechanistic pathway was proposed and elucidated through intermediate mass analysis, supported by Density Functional Theory (DFT) calculations.

Highly scalable and robust ribbon-like coordination polymer as green catalyst for Hantzsch condensation in synthesis of DHPs and bioactive drug molecule

Ribbon-like coordination polymers (CP) represents a highly unexplored innovative class of metal-coordination network. Herein, we have developed a highly scalable and chemically robust (pH = 3–10 stable) ribbon-like CP [{Cu(Pim)(L)(H2O)·H2O}]n(1) following a complete environment-friendly green synthesis route. Considering the presence of surface flanked labile coordinated water molecules and their appealing correlation with one-dimensional structural characteristics, such sort of ribbon-like CP was explored for the first time as excellent heterogeneous surface catalyst for largely unexplored three-component Hantzsch condensation for synthesis of different classes of dihydropyridine (DHP). Moreover, 1 is employed to synthesize bio-responsive drug ‘Ethidine’ (possessing high anti-oxidant and anticarcinogenic properties) characterized with Single Crystal X-ray Diffraction (SCXRD) analysis. Several DHP-based products are also analysed through in-depth SCXRD analysis. This report inaugurates the usage of a Cu(II) based ribbon-like CPs as heterogeneous surface catalyst following environmentally benign manner for synthesis of bioactive DHPs and Drugs.

Microwave-assisted synthesis of base-modified fluorescent 1,4-dihydropyridine nucleosides: photophysical characterization and insights.

A synthesis of a small library of fluorescent 1,4-dihydropyridine nucleoside analogues has been successfully carried out under solvent-free conditions via a one-pot three-component Hantzsch condensation reaction. The process involved a Ba(NO3)2 catalyzed solvent-free reaction between 3',5'-di-O-acetyl-5-formyl-2'-deoxyuridine, differently substituted β-keto ester and ammonium acetate under microwave irradiation. This facile methodology yielded the desired products with very high yields (86-96%) under solvent-free reaction conditions in a short reaction time, which was followed by a simple workup. Yields obtained under microwave and conventional heating were compared, with the microwave irradiation condition displaying superior results. The synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, 1H-1H COSY, 1H-13C HETCOR, 2D NOESY NMR and HRMS analysis. These nucleoside analogues exhibited significant fluorescence, with a prominent emission band around 460 nm (excitation at 235 nm). Photophysical studies revealed strong fluorescence intensity, excellent Stokes shifts (70-162 nm), and high quantum yields (0.022-0.579), outperforming other pyrimidine-based fluorescent nucleosides. Notably, 5-(diethyl 2'',6''-propyl-1'',4''-dihydropyridine-3'',5''-dicarboxylate)-4''-yl-2'-deoxyuridine demonstrated a quantum yield as high as 0.579 in DMSO during solvatochromic studies, highlighting their potential for probing local nucleic acid structure and dynamics. Additionally, we demonstrated the scalability of the synthesis protocol by producing one of the compounds on a gram scale, confirming its practical viability for large-scale production. This study underscores the potential of these fluorescent nucleoside analogues for various biochemical applications.

Synthesis of poly(pyrazolopyridine)s by Hantzsch multicomponent polymerization

This work concerns the synthesis of poly(pyrazolopyridine)s via a three-component Hantzsch reaction. The first part of this study was intended to determine adequate experimental conditions for the synthesis of an analytically pure pyrazolopyridine heterocycle model compound in quantitative yield, which can be further used for polymer synthesis. For this purpose, the effect of different parameters (solvent, temperature, additive) on the selectivity of the reaction has been investigated. Some specific difunctional precursors (bisaminopyrazoles and dialdehydes) have been then designed and synthesized. From these reagents, poly(pyrazolopyridine)s were successfully synthesized by multicomponent polycondensation reaction. Some physico-chemical characterizations of these new macromolecular structures are described. • Multi-component reactions broaden the scope of conventional polycondensation. • Unconventional synthesis of aromatic and heterocyclic polymers by Hantzsch reaction. • Poly(pyrazolopyridine)s can be synthesized by multi-component polycondensation.

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.

Zn/MCM-41-catalyzed unsymmetrical Hantzsch reaction and the evaluation of optical properties and anti-cancer activities of the polyhydroquinoline products

The three-component Hantzsch condensation of various aryl aldehydes, dimedone, and methyl 3-aminocrotonate was investigated in the presence of MCM-41-supported ZnNO3. The polyhydroquinoline products which were obtained under mild conditions and very easy workup were evaluated for anti-cancer activities against MCF-7, SK-BR-3, and HT-29 of breast and colon cancer cells. The fluorescence emission of some products was also studied and their optical parameters were reported.

Microwave-promoted three-component Hantzsch synthesis of acridinediones under green conditions

Microwave-promoted three-component Hantzsch synthesis of acridinediones under green conditions

Synthesis of alkyne-tagged and biotin-tagged Sortin1 as novel photoaffinity probes

Sortin1 is an inhibitor of vesicular biogenesis and transport, which is shared among eukaryotes and plants with an unknown mode of action. Toward exploration of its target proteins, we developed alkyne as well as biotin conjugated photoaffinity probes derived from Sortin1. Due to the presence of phenylketone moiety, Sortin1 was anticipated to serve as a photoreactive group in a similar manner to a commonly used photoreactive group, benzophenone. The core structure based on 5-oxo-1,4-dihydroindenopyridine was constructed in one step using three-component Hantzsch dihydropyridine synthesis. We demonstrated that Sortin1 displayed photocrosslinking reactivity against a model binding protein, which would be useful for capturing and detecting binding proteins.

Graphite oxide-promoted one-pot synthesis and oxidative aromatization of Hantzsch 1,4-dihydropyridines

A new and efficient method for the one-pot synthesis of pyridine compounds using three-component Hantzsch synthesis in high yields using graphite oxide, a readily available and inexpensive material, as a mild and efficient agent is described.

Synthesis of 2,3-dicarbonylated pyrroles and furans via the three-component Hantzsch reaction

Pyrroles containing a 2,3-dicarbonyl substitution pattern are synthesized in one step via a three-component Hantzsch procedure. The normally difficult-to-access substrates are readily obtained in short reaction times and in moderate to good yields, giving pharmaceutically attractive products containing multiple handles for further elaboration.

General Synthesis of Hantzsch Esters in 2,2,2-Trifluoroethanol

Reported is the standard three-component Hantzsch synthesis of 1,4-dihydropyridines (acetoacetate ester, ammonium acetate and aldehyde) under new conditions - in 2,2,2-trifluoroethanol (TFE) . The reaction proceeds rapidly at 70 ˚C to afford the 1,4-dihydropyridines in very good yields (÷95%). The reaction shows broad scope for aldehydes (aliphatic, aromatic, hetero­aromatic and α,β-unsaturated). An unsymmetrical Hantzsch reaction (cyclic 1,3-diketone, aldehyde, acetoacetate and ammonium acetate) was also realized under the same conditions to afford polyhydroquinolines in good to excellent yields. Further, the synthesis of two 1,8-dioxodecahydro-acridines starting from cyclic 1,3-diketone and ­aromatic aldehydes was described.

An efficient one-step synthesis of 1,4-dihydropyridines via a triphenylphosphine-catalyzed three-component Hantzsch reaction under mild conditions

An efficient one-step synthesis of 1,4-dihydropyridines in good to excellent yields via the triphenylphosphine-catalyzed Hantzsch three-component reaction of an aromatic aldehyde, ethyl acetoacetate and ammonium acetate is described.

Two- and Three-Component Hantzsch Reaction Using C-Glycosylated Reagents. Approach to the Asymmetric Synthesis of 1,4-Diyhydropyridines

Two- and three-component Hantzsch-type cyclocondensation reactions were carried out under thermal conditions using C-glycosylated reagents, namely sugar aldehydes, ketoesters, and enamines. Two different series of 1,4-dihydropyridines bearing C-glycosyl moieties at C4 and C6 were obtained in good to excellent overall yields (61-90%). The asymmetric induction due to carbohydrate residues was also investigated.