One-pot Four-component Reaction Research Articles

ChemInform Abstract: Organocatalytic Cascade Michael/Michael Reaction for the Asymmetric Synthesis of Spirooxindoles Containing Five Contiguous Stereocenters.

A bifunctional squaramide-catalyzed Michael/Michael cascade reaction for the construction of five-membered spirooxindoles was developed. This reaction afforded the corresponding products with five contiguous stereocenters including a quaternary center in good to excellent yields (up to 93%) with excellent stereoselectivities (up to >99:1 dr, 98% ee). Meanwhile, the practicality of this methodology was illustrated by a gram-scale synthesis, one-pot four-component reaction and synthetic transformation of the resulting adduct.

ChemInform Abstract: Four‐Component Reaction of Substituted β‐Nitrostyrenes, Cyclohexanones, Activated Methylene Compounds, and Ammonium Acetate: Efficient Strategy for Construction of Tetrahydroindole Skeletons.

An efficient one-pot four-component reaction was developed for the synthesis of two different stereochemical classes of substituted 2-aminotetrahydroindoles from substituted β-nitrostyrenes, cyclohexanones, ammonium acetate, and activated methylene compounds, such as Meldrum’s acid, 4-hydroxycoumarin, cyclohexanediones, cyclopentane-1,3-dione, or alkyl cyanoacetates. Both electron-donating and electron-withdrawing groups are tolerated in the aryl ring of the β-nitrostyrene. The reaction utilizes the triethylamine-promoted formation of new C–C and C–N bonds, and simultaneous aromatization in a domino fashion.

H3PMo12O40 immobilized chitosan/Fe3O4 as a novel efficient, green and recyclable nanocatalyst in the synthesis of pyrano-pyrazole derivatives

A novel nanomagnetic composite heteropolyacid immobilized chitosan/Fe3O4 was prepared via a facile one-pot synthetic approach. This magnetically recoverable nanocatalyst, H3PMo12O40/chitosan/Fe3O4 (PMo/chit/Fe3O4), was fully characterized by XRD, FTIR, SEM and EDX analysis methods. A rapid, efficient and the chemoselective synthesis of different pyrano-pyrazole derivatives was achieved in excellent yields via a one-pot four-component reaction in the presence of catalytic amount of PMo/Chit/Fe3O4.

Synthesis and biological evaluation of some functionalized 1H-1,2,3-triazole tethered pyrazolo[3,4-b]pyridin-6(7H)-ones as antimicrobial and apoptosis inducing agents

A series of novel molecular hybrids containing pyrazole, pyridinone and 1,2,3-triazoles have been synthesized by one-pot four-component reaction of Meldrum’s acid, substituted aryl azides, 4-(prop-2-yn-1-yloxy)aryl aldehyde and 3-methyl-1-phenyl-1H-pyrazol-5-amine using L-proline as a basic organocatalyst besides CuSO4.5H2O and sodium ascorbate as catalysts for click chemistry in PEG-400 as a highly efficient and green media. Apoptosis studies have been carried out on ovarian follicles of goat (Capra hircus) and in vitro antibacterial activity has been done against six strains namely Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa and antifungal activity against two yeast strains namely, Candida albicans and Saccharomyces cerevisiae.

Tartaric Acid: A Naturally Green and Efficient Di-Functional Brønsted Acid Catalyst for the One-Pot Four-Component Synthesis of Polysubstituted Dihydropyrrol-2-Ones at Ambient Temperature

A series of biologically active polysubstituted dihydropyrrol-2-ones are prepared via a one-pot four-component reaction of structurally diverse dialkyl acetylenedicarboxylate, formaldehyde, and amines (aromatic and aliphatic) using a catalytic amount of tartaric acid as a naturally green, mild di-functional Bronsted acid catalyst at ambient temperature. The use of tartaric acid as an inexpensive catalyst makes this procedure eco-friendlier and also one-pot, easily separated from the reaction mixture, good to high yields, short reaction times, simple operational procedures, and highly efficient that are the added advantages of the present methodology.

Multicomponent synthesis of diverse pyrano-fused benzophenazines using bifunctional thiourea-based organocatalyst in aqueous medium.

A series of pyrano-fused benzophenazines were synthesized using a bifunctional thiourea-based organocatalyst from the one-pot four-component reaction of 2-hydroxy-1,4-naphthoquinone, benzene-1,2-diamines, malononitrile or its derivatives and isatins or aromatic aldehydes in aqueous medium. Metal-free reaction condition, water as solvent, high bond forming efficiency (five new bonds formed in one step), good yields and easy purification process are the notable features of this methodology.

Chitosan: a sustainable, reusable and biodegradable organocatalyst for green synthesis of 1,4-dihydropyridine derivatives under solvent-free condition

Chitosan, a biodegradable green catalyst, was found to be an impressive system for one-pot four-component reaction of different aldehydes, dimedone, β‐ketoesters or acetoacetanilide, and ammonium acetate leading to 1,4-dihydropyridine derivatives via Hantzsch-type condensation under solvent-free condition. This methodology produces diverse superiorities such as operational simplicity, short reaction time, satisfied yield and recyclable catalyst. In this work, we attempted to develop several modifications for the classical Hantzsch conversion to report a novel eco-friendly method that is free from previously reported disadvantages.

ClO4 −/Zr-MCM-41 nanoparticles prepared at mild conditions: a novel solid acid catalyst for the synthesis of polyhydroquinolines

One-pot four-component reaction of aldehydes, dimedone, ethyl cyanoacetate or ethyl acetoacetate and ammonium acetate was studied in the presence of perchlorated Zr-MCM-41 (ClO4−/Zr-MCM-41) nanoparticles for the synthesis of dihydropyridines. Zr-MCM-41 nanoparticles with various molar ratios of Si/Zr were synthesized by sol–gel method under mild conditions, and then ClO4−/Zr-MCM-41 samples with different calcination temperatures were prepared and characterized by XRD, FT-IR and SEM techniques. The characterization results show the presence of perchlorate in the mesostructure of Zr-MCM-41 and the catalytic performance experiments show that ClO4−/Zr-MCM-41 with Si/Zr molar ratio of 25 and calcinations temperature of 300 °C has the best catalytic activity. The catalyst can be recovered easily and reused many times with moderate decrease in activity.

A green and efficient four-component sequential protocol for the synthesis of novel 16-(aryl)benzo[a]indeno[2′,1′:5,6]pyrano[2,3-c]phenazin-15(16H)-one derivatives using oxalic acid as a reusable and cost-effective organic catalyst

A sequential one-pot four-component reaction for the efficient synthesis of novel 16-(aryl)benzo[a]indeno[2′,1′:5,6]pyrano[2,3-c]phenazin-15(16H)-one derivatives has been developed. The synthesis was achieved by reacting 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamine, aromatic aldehydes, and 1,3-indandione in the presence of oxalic acid as a reusable and homogenous organocatalyst in EtOH/H2O (1:1) under reflux. The present approach of this methodology offers several advantages such as high yields, clean reaction profiles, operational simplicity, simple work-up procedures, and green aspects by avoiding toxic catalysts and solvents.

Green and facile synthesis of dihydropyrrol-2-ones and highly substituted piperidines using ethylenediammonium diformate (EDDF) as a reusable catalyst

Extremely facile and efficient procedures have been developed for the synthesis of dihydropyrrol-2-ones and highly substituted piperidines. One-pot four-component reaction of amines, dialkyl acetylenedicarboxylates, and formaldehyde in the presence of ethylenediammonium diformate in ethanol under reflux conditions provides N-aryl-3-amino dihydropyrrol-2-one-4-carboxylates in good to high yields. The same conditions were found useful for the synthesis of highly substituted piperidines via a three (pseudo five)-component reaction of amines, aldehydes, and β-ketoesters. It is found that the catalyst is reusable and can be used up to five times without significant loss of its activity.

A synthesis of spirofuran-indenoquinoxalines via isocyanid-based one-pot four-component reaction

Abstract A simple and versatile procedure for the combinatorial synthesis of ( Z )-dialkyl-5-(alkylimino)-5 H -spiro[furan-2,11′-indeno[1,2- b ]quinoxaline]-3,4-dicarboxylates via the catalyst-free one-pot four-component reaction of ninhydrin, benzene-1,2-diamines, dialkyl acetylenedicarboxylates and isocyanides is described.

Synthesis of 1,2,3-Triazolylmethoxyphenyl[1,2,4]triazolo[1,2-a]in­dazoletrione Derivatives by Combining Click and Multicomponent Reactions

The one-pot four-component reaction of propargylated benzaldehydes, azide, dimedone, and urazoles in the presence of melamine trisulfonic acid, copper acetate, and sodium ascorbate was used for the synthesis of 1,2,3-triazolylmethoxyphenyl[1,2,4]triazoloindazole-1,3,8-trione derivatives as novel compounds.

A comparative study on the catalytic activity of Fe3O4@SiO2–SO3H and Fe3O4@SiO2–NH2 nanoparticles for the synthesis of spiro [chromeno [2, 3-c] pyrazole-4, 3′-indoline]-diones under mild conditions

Sulfuric acid and (3-aminopropyl)-triethoxysilane were successfully attached to the core–shell structure of Fe3O4@SiO2 nanoparticles separately. The prepared nanoparticles were characterized by vibrating sample magnetometer, powder X-ray diffraction, scanning electronic microscopy, thermal gravimetric analysis, energy dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. To compare the efficiency of the two prepared functionalized magnetic nanoparticles, they were employed as catalysts for the synthesis of spirooxindole containing chromene ring fragments in one-pot four-component reactions. Sulfuric acid-functionalized magnetic nanoparticles showed high catalytic activity in mild reaction conditions and short reaction times and excellent yields of products. The catalyst was easily separated using a magnet and reused for several cycles of reactions without any significant loss of catalytic activity.

One-pot synthesis and antimicrobial evaluation of novel 3-cyanopyridine derivatives of (−)-β-pinene

A series of novel 3-cyanopyridine derivatives of (−)-β-pinene were designed and synthesized by one-pot four-component domino reactions. The targeted compounds were evaluated for their antimicrobial activity against four bacteria (Klebsiella pneumoniae, Enterobacter aerogenes, Staphylococcus aureus, Staphylococcus epidermidis) and a fungus (Candida albicans). The results showed that most of the minimal inhibitory concentrations (MICs) of these 3-cyanopyridine derivatives against the tested strains was in the range of 15.6–125mg/L. Among these 3-cyanopyridine derivatives, the MICs of compound 5h against S. epidermidis and C. albicans were 15.6mg/L, which revealed that compound 5h featured double fluoro substituents at meta- and para-position was the most active compound. In addition, the preliminary structure–activity relationship analysis indicated that the change of substituents on the pyridine ring and benzene ring of 3-cyanopyridine derivatives was an important factor for inducing antimicrobial activity. This research would promote the development of heterocyclic derivatives of β-pinene with antimicrobial activity.

ChemInform Abstract: Convenient One‐Pot Room Temperature Synthesis of 2‐(Trifluoromethyl)‐1,2,3,4,7,8‐hexahydroquinolin‐5(6H)‐one Derivatives via Catalyst‐Free Multicomponent Reactions.

This paper describes an efficient approach for the synthesis of 2-(trifluoromethyl)-1,2,3,4,7,8-hexahydroquinolin-5(6H)-one derivatives via a one-pot four-component reaction of aromatic aldehyde, 5,5-dimethylcyclohexane-1,3-dione, 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione, and NH4OAc with excellent yields at room temperature. In this synthesis, the trifluoromethyl was efficiently introduced in hexahydroquinoline structure, and they may be valuable the drug candidates. This approach also offered several other advantages, such as catalyst-free, mild conditions, and simple experimental operation.

Microwave assisted highly efficient one-pot multi-component synthesis of novel 2-(tetrasubstituted-1H-pyrrol-3-yl)-4H-chroman-4-ones catalyzed by heterogeneous reusable silica gel supported polyphosphoric acid (PPA/SiO2)

A solvent-free, eco-friendly and facile approach for the synthesis of highly functionalized tetrasubstituted pyrroles has been reported through one-pot four-component reaction of aldehyde, amine, nitroalkane and 1,3-diketone using silica gel supported polyphosphoric acid (PPA–SiO2) under microwave condition. The reaction occured through the in situ formation of β-keto enamine and nitrostyrene analog following Michael addition and finally intramolecular annulation affording the products in good yields. The key features of the present method include clean reaction, mild conditions, low catalyst loading, straightforward, high to excellent yields, short reaction time, avoiding use of harmful metal catalyst and organic solvent, environmentally friendly compared to the existing methods, recovery and reusability of catalyst and easy workup procedure.

Four-Component Reaction of Substituted β-Nitrostyrenes, Cyclohexanones, Activated Methylene Compounds, and Ammonium Acetate: Efficient Strategy for Construction of Tetrahydroindole Skeletons

An efficient one-pot four-component reaction was developed for the synthesis of two different stereochemical classes of substituted 2-aminotetrahydroindoles from substituted β-nitrostyrenes, cyclohexanones, ammonium acetate, and activated methylene compounds, such as Meldrum’s acid, 4-hydroxycoumarin, cyclohexanediones, cyclopentane-1,3-dione, or alkyl cyanoacetates. Both electron-donating and electron-withdrawing groups are tolerated in the aryl ring of the β-nitrostyrene. The reaction utilizes the triethylamine-promoted formation of new C–C and C–N bonds, and simultaneous aromatization in a domino fashion.

Ultrasound mediated, green innovation for the synthesis of polysubstituted 1,4-dihydropyridines

An atom efficient protocol via a one-pot four-component cyclocondensation reaction catalyzed by copper(i) iodide in aqueous medium under ultrasonic irradiation has been developed for the synthesis of novel polysubstituted 1,4-dihydropyridines.

Nano-ferrite supported glutathione as a reusable nano-organocatalyst for the synthesis of phthalazine-trione and dione derivatives under solvent-free conditions

Nano-organocatalyzed one-pot four-component reactions for the synthesis of phthalazine-trione/dione derivatives have been devised for the first time from easily accessible starting materials under solvent-free conditions.

Alkaline-Earth-Catalyzed sp3 C–H Functionalization of Methyl Azaarenes and Its Use in a One-Pot Four-Component Synthesis of Azaarenyl Benzylpyrazolones

The sp³ C–H functionalization of methyl azaarenes by using calcium triflate as the catalyst is described, together with its use in the first synthesis of azaarenyl benzylpyrazolones by a one-pot four-component reaction.