Arylglyoxal Monohydrates Research Articles

Ethylene Glycol Mediated, Catalyst-Free Synthesis of Bis(pyrazolo) pyridines and Their Photophysical Studies

AbstractA new hetero-annulation procedure for the selective synthesis of bis(pyrazolo)-fused pyridines using pyrazole-5-amines and aryl glyoxal monohydrate is described. This distinct hetero-annulation, carried out under catalyst-free conditions with ethylene glycol as the medium, illustrates a domino reaction that involves the formation of two C–C bonds and one C–N bond. The photophysical properties of the synthesized derivatives were briefly analyzed. The emission spectra of the derivatives exhibited distinct charge transfer peaks, which depends on the structure of the derivatives. The green metrics calculation for the protocol to quantify the waste, reaction efficiency, and sustainability was evaluated.

Multicomponent synthesis of 3-(1H-indol-3-yl)-2-phenyl-1H-benzo[f]indole-4,9-dione derivatives.

Herein, we report a one-pot greener methodology for the synthesis of 3-(1H-indol-3-yl)-2-phenyl-1H-benzo[f]indole-4,9-dione derivatives by the multicomponent reaction of arylglyoxal monohydrate, 2-amino-1,4-naphthoquinone, and indole in acetonitrile medium under reflux conditions in the presence of 10mol% sulfamic acid as a catalyst in 20-30min of reaction time. Three new bonds have formed (2 C-C, 1 C-N) in this methodology. Bioactive moieties such as indole, pyrrole and naphthoquinone are present in our product. This methodology is also applicable in gram-scale synthesis. A wide variety of substrates were tested to find the generality of the methodology and good yield of the products were obtained in a very short reaction time. Along with the operational simplicity of the methodology, purification process of the products is easier by simple recrystallization process. All the synthesized products were characterized by spectroscopic techniques such as FTIR, 1H NMR, 13C NMR, and HRMS.

Synthesis Of Dipyrrolobenzo[1,2‐a : 2′,1′‐c][1,4]diazepine Scaffold Via Three‐Component Reaction

AbstractA three component reaction employing readily available starting materials: 2‐(1‐pyrrolyl)benzylamine, arylglyoxal monohydrates and electron‐deficient alkenes in the synthesis of dipyrrolobenzo[1,2‐a : 2′,1′‐c][1,4]diazepines ‐ previously undescribed system and indolo[2,1‐c]pyrrolo[1,2‐a][1,4]benzodiazepine derivatives have been shown. Domino reactions of pyrrolo[1,2‐a][1,4]benzodiazepines with electron‐deficient alkenes has been proposed as another approach. The applicability of the three‐component reaction for the synthesis of indolizino[8,7‐b]indole derivatives from tryptamine has been studied. The in vitro biological activity of title compounds has been tested.

Bi(iii)-catalyzed synthesis of furocoumarins via a three component reaction of arylglyoxal monohydrates, coumarins and N-substituted anilines

We unveil an operationally robust route to a new library of furocoumarin derivatives via a three-component reaction involving arylglyoxal monohydrates, 4-hydroxycoumarins and N-substituted anilines.

Domino Reaction for the Synthesis of Pyrazole/Isoxazole Fused Naphthyridine Derivatives Involving Indole Ring Opening and Double Ring Formation

Herein, a hitherto unreported approach for the synthesis of pyrazole/isoxazole-fused naphthyridine derivatives by a three-component domino reaction of arylglyoxal monohydrate, 5-amino pyrazole/isoxazole, and indoles in acetic acid medium has been reported. In this method, four bonds (2 C-C and 2 C-N) form in one-pot with the concomitant formation of two new pyridine rings via indole ring opening and double cyclization reactions. This methodology is also applicable in gram-scale synthesis. The reaction mechanism was studied by isolating and characterizing the reaction intermediates. Along with complete characterization of all the products, the structure of the product 4o was unambiguously confirmed by single crystal X-ray diffraction.

5-(1-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-phenylethyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione

Multicomponent reactions have been demonstrated as a promising tool for the creation of diverse molecular structures with enhanced efficiency, reduced waste, and a high atom economy. Arylglyoxal monohydrates with two different carbonyl groups are well known as worthwhile synthons in organic synthesis. 2-Pyrone and pyrimidine-2,4,6-trione are versatile building blocks for the synthesis of key intermediates in synthetic organic chemistry as well as in medicinal chemistry. A simple and efficient tandem Knoevenagel–Michael protocol for the synthesis of the previously unknown 5-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-phenylethyl)-1,3-dimet-hylpyrimidine-2,4,6(1H,3H,5H)-trione was elaborated. The suggested method is based on the multicomponent reaction of phenylglyoxal hydrate, 1,3-dimethylbarbituric acid, and 4-hydroxy-6-methyl-2H-pyran-2-one. The structure of the synthesized compound was proven by 1H, 13C-NMR, and IR spectroscopy, mass spectrometry, and elemental analysis. A procedure for predicting the possible types of its biological activity was carried out for the title compound.

The synthesis of novel 2, 3‐disubstituted 1,6‐dihydropyrrolo[2,3‐g]indazole derivatives via one‐pot three component reactions

AbstractA concise and efficient synthetic approach was developed for the synthesis of functionalized 2,3‐disubstituted 1,6‐dihydropyrrolo[2,3‐g]indazole via a one‐pot, three‐component reaction of 1H‐indazol‐6‐amine, arylglyoxal monohydrates, and 4‐hydroxy‐2H‐chromen‐2‐one or 4‐hydroxyquinolin‐2(1H)‐one promoted by acetic acid in ethanol under reflux conditions. The attractive features of this protocol are operational simplicity, short reaction time, easy purification of products, and good to excellent yields.

Para toluenesulfonic acid-catalyzed one-pot, three-component synthesis of benzo[5,6]chromeno[3,2-c]quinoline compounds in aqueous medium

Abstract A new series of benzo[5,6]chromeno[3,2-c]quinoline derivatives were successfully synthesized using various arylglyoxal monohydrates, quinoline-2,4-dione, and β-naphthol in H2O:EtOH (2:1) as a green solvent in the presence of catalytic amounts p-toluenesulfonic acid as a mild catalyst under reflux conditions with high yields (83–92%). The reaction conditions were optimized in different solvents at variable thermal conditions, and the optimized reaction condition for this synthesis has been reported. The structures of all new products were defined by 1H-NMR, 13C-NMR, FT-IR, mass spectral data, and HRMS.

Microwave assisted novel one-pot three-component reaction for synthesis of 3-aminoimidazopyridines using molecular iodine

An expedient, cost-effective and metal-free green protocol has been developed for the preparation of 3-aminoimidazopyridines by the three-component reaction of arylglyoxal monohydrates, aromatic amines and 2-aminopyridines. This multicomponent reaction was executed under microwave irradiation in presence of catalytic amount of molecular iodine in ethanol, involving the formation of three new CN bonds via imine intermediate. Environmentally benign catalyst, eco-friendly medium, good yields, short reaction time and purification by simple crystallization are some distinguished features of this protocol. In addition, presented method is sustainable since produced water only as by product, avoidance of toxic catalyst and good amenability with principle of green chemistry.

Lewis‐Acid‐Mediated One‐Pot Tandem Reactions for Synthesis of Structurally Diverse Furo[3,2‐c]coumarins

AbstractA concise, one‐pot route for the synthesis of furo[3,2‐c]‐coumarins under the catalysis of Zn(OTf)2 is reported. Utilizing this synthetic strategy, libraries of furocoumarin analogues can be easily obtained by multicomponent tandem reactions with different nucleophile in the presence of 4‐hydroxycoumarin and arylglyoxal monohydrate system, This transformation exhibited highly atom economical and good functional group compatibility.

Acetic acid promoted an efficient and eco-friendly one-pot synthesis of functionalized novel isoxazolyl amino chromenopyrrole derivatives in aqueous medium

An efficient, economical, and environmentally friendly method has been reported for one-pot synthesis of isoxazolyl amino chromenopyrrole derivatives from 4-amino-3-methyl-5-styrylisoxazoles, aryl glyoxal monohydrates and 4-aminocoumarins by using acetic acid (AcOH) as a green promoter and water as a reaction medium under heating condition. The attractive features of this method are operational simplicity, environmentally friendly, metal-free, shorter reaction time, broad substrate scope, easy purification of products and good to excellent yields. Most important of all, this one-pot method is green.

A new and facile synthesis of 3-(2-aryl-6-nitro-1H-indol-3-yl)quinoline-2,4(1H,3H)-diones by sodium alginate as biopolymeric catalyst

New 3-(2-aryl-6-nitro-1H-indol-3-yl)quinoline-2,4(1H,3H)-diones were synthesized, and good-to-excellent yields were achieved through one-pot, three-component condensation of aryl glyoxal monohydrates, 4-hydroxyquinolin-2(1H)-one and 3-nitroaniline using sodium alginate and water/ethanol (1:1) as a green solvent at mild reaction conditions. The noticeable features of the present procedure are mild reaction conditions, economic procedure, availability of starting materials, very simple operation, easy isolation, no need for column chromatography separation and using sodium alginate as a natural polysaccharide that is a transition-metal-free, biodegradable, reusable and commercially affordable catalyst. In addition, sodium alginate was recycled up to five times with no remarkable loss of its catalytic properties.

Fast and Efficient Green Procedure for the Synthesis of Benzo[5,6]chromene Derivatives and Their Sulfur Analogues in Water by Organocatalyst Potassium Phthalimide-N-oxyl

A simple, clean, straightforward, and environmentally benign one-pot, three-component reaction of various arylglyoxal monohydrates, β-naphthol, and barbituric acid [pyrimidine-2,4,6(1H,3H,5H)-trione] or thiobarbituric acid in the presence of catalytic amounts potassium phthalimide-N-oxyl (PPINO), as a mild and efficient organocatalyst in aqueous media under reflux conditions is reported. This transformation produced the novel diverse-substituted 12-benzoyl-8,12-dihydro-9H-benzo[5,6]chromeno[2,3-d]pyrimidine-9,11(10H)-diones and their sulfur analogues in 82–93% yield via filtration and without utilization of any chromatography. The high yields of products, very simple operation, easy workup, availability of starting materials, green process, and high atom-economy are the main benefits of this synthetic strategy.

Multicomponent Cascade Reaction by Metal-Free Aerobic Oxidation for Synthesis of Highly Functionalized 2-Amino-4-coumarinyl-5-arylpyrroles.

A novel approach has been constructed for the synthesis of two types of 2-amino-4-coumarinyl-5-arylpyrroles (ACAPs, 5 and 6) through a cascade reaction and a metal-free catalyzed aerobic oxidation reaction of arylglyoxal monohydrates 1, 1,1-enediamines (EDAMs) 2 and 3, and 4-hydroxy-2H-chromen-2-ones 4 via multicomponent reactions to produce the target compounds with good to excellent yields. Specifically, hydroxyl-substituted 2-amino-4-coumarinyl-5-arylpyrroles, that is, 2-amino-4-coumarinyl-5-aryl-6-hydroxylpyrroles (ACAHPs) 6, were obtained by metal-free aerobic oxidation in 1,4-dioxane at simple reflux for approximately 10 h. As a result, ACAHPs 6 have been produced without metal catalysts or traditional oxidizing agents. This method represents a route to obtain the novel ACAPs in an environmentally friendly, concise, rapid, and practical manner with potential biological activity of the product.

A Facile and Effective Procedure for Synthesis of Polyfunctionalized Bis (imidazolyl) Pyrrole/Imidazolyl Indole from Pyrrole/Indole with Arylglyoxals and N‐aryl amidines

Heterocyclic systems containing bis (imidazolyl) pyrrole or imidazolyl indole moieties were synthesized by heterocyclization of pyrrole or indole with arylglyoxal monohydrates and N‐aryl amidines in ethanol catalyzed by FeCl3 at room temperature. The paper reports a facile, efficient, and environmentally friendly protocol for the synthesis of new products. Products were isolated by simple filtration, and their structures were established from their spectroscopic data.

Synthesis of Furo[3,2‐c]coumarins via Lewis Acid‐Mediated Multicomponent Tandem Reactions

An efficient method for the synthesis of furo[3,2‐c]coumarins through FeCl3 or ZnCl2‐mediated multicomponent tandem reactions in the presence of arylglyoxal monohydrates, 4‐hydroxycoumarin, and allyltrimethylsilane in toluene is reported. This reaction involves the formation of two C‐C bonds and one C‐O bond. This process provided the privileged structures of furo[3,2‐c]coumarins in moderate to good yields under mild conditions. Notable features of the procedure such as easily accessible starting materials, good functional group tolerance, and high atom economy have been developed.

Multicomponent Tether Catalysis Synthesis of Highly Functionalized 4-(Pyridin-2-ylmethyl)-2-aminopyrroles via Cascade Reaction Is Accompanied by Decarboxylation.

A multicomponent tether catalysis protocol for the synthesis of 4-(pyridin-2-ylmethyl)-2-aminopyrroles (PMAPs) was constructed by simply refluxing a mixture of ethyl 2-(pyridin-2-yl)acetates 1 and various types of arylglyoxal monohydrates 2 and different heterocyclic ketene aminals 3 in EtOH solvent. Based on this reaction, a series of highly functionalized PMAPs were obtained through a novel cascade reaction accompanied by a decarboxylation mechanism. As a result, the pyridin-2-ylmethyl was successfully introduced in the target compounds, and a library of PMAPs were easily constructed using the cascade reaction described in this study. This protocol demonstrated that the most important feature was the decarboxylation reaction of the 2-(pyridin-2-yl)acetates 1, which can be used in the synthesis of pyridin-2-ylmethyl-substituted heterocycles, including pyrroles, pyridines, quinolones, and other heterocyclic compounds resembling those found in nature.

Water-acetic acid mediated an efficient one-pot eco-friendly synthesis of novel bis-isoxazolopyrroloquinoline derivatives

An efficient, cost-effective and environmentally benign synthesis of novel tetracyclic bis-isoxazolopyrroloquinoline derivatives has been developed via one-pot four-component reaction of 4-amino-3-methyl-5-styrylisoxazoles, dimedone, aryl glyoxal monohydrates and 5-amino-3-methylisoxazole by employing water as a reaction medium and acetic acid (AcOH) as a green promoter. The advantages of this protocol are environmentally friendly, metal-free, less reaction time, operational simplicity, high yields, broad substrate scope and easy purification. Most significant of all, this method is green.

An efficient and novel protocol for the synthesis of spiro[1,3]oxazino[5,6-c]quinoline derivatives by one-pot, three-component reaction

One-pot, three-component reaction of various aryl glyoxal monohydrates, 5-methylisoxazol-3-amine and 4-hydroxyquinolin-2(1H)-one in the presence of a catalytic amount of DBU in H2O/EtOH (1:1) at 50 °C produced the 4-aroyl-5′-methyl-3,4-dihydro-2′H-spiro[[1,3]oxazino[5,6-c]quinoline-2,3′-isoxazol]-5(6H)-one derivatives containing spiro[1,3]oxazino[5,6-c]quinoline moiety in 82–89% yield. The high yields of products, easy work-up, and availability of starting materials are the main advantages of this synthetic strategy.

Facile one-pot synthesis of novel highly functionalized dihydro-1H-pyrrole derivatives catalyzed by molecular iodine

An efficient, environmentally benign and molecular iodine promoted protocol was described for cascade synthesis of two kinds of novel dihydro-1H-pyrrole derivatives, 5 and 7. Compounds 5 were prepared via four-component reaction between diethyl acetylenedicarboxylate (DEAD), aromatic amines and phenylglyoxal monohydrate catalyzed by 10 mol% of iodine in ethanol at room temperature. In addition, using same reaction conditions, a three-component reaction between (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), aromatic amines and arylglyoxal monohydrate was performed to access product 7. These transformations apparently proceed through an imine intermediate followed by iodine induced Mannich reaction and subsequent intra-molecular cyclization sequences. The protocol involves the formation of CN, CC and OH bonds leading to the preparation of a hexa substituted five membered ring with two stereo centres. The syntheses avoid the use of traditional column chromatography and recrystallization purification methods and, hence, follow the group-assisted purification (GAP) chemistry process.