Tandem Knoevenagel Condensation Research Articles

Heterobimetallic Synergism in Triple-Redox 2D Framework for Largely Boosted Water Oxidation and Flanked Carboxylic-Acid-Triggered Unconventional Tandem Catalysis.

A fish-bone-shaped and thermochemically stable 2D metal-organic framework (MOF) with multimodal active center-decked pore-wall is devised. Redox-active [Co2(COO)4] node and thiazolo[5,4-d]thiazole functionalization benefit this mixed-ligand MOF exhibiting electrochemical water oxidation with 375mV overpotential at 10mA cm-2 current density and 78mV per dec Tafel slope in alkaline medium. Pair of oppositely oriented carboxylic acids aids postmetalation with transition metal ions to engineer heterobimetallic materials. Notably, overpotential of Ni2+ grafted triple-redox composite reduces to 270mV with twofold declined Tafel slope than the parent MOF, ranking among the best-reported values, and outperforming majority of related catalysts. Significantly, turnover frequency and charge transfer resistance display 35.5 and 1.4-fold upsurge, respectively, with much uplifted chronopotentiometric stability and increase active surface area owing to synergistic Co(II)-Ni(II) coupling. The simultaneous presence of ─COOH and nitrogen-rich moieties renders this hydrogen-bonded MOF as acid-base synergistic catalyst for recyclable deacetalization-Knoevenagel reaction with >99% product yield under solvent-free mild condition. Besides control experiments, unique role of ─COOH as hydrogen-bond donor site in substrate activation is validated from comparing the performances of molecular-shearing approach-derived structurally similar unfunctionalized MOF, and the heterobimetallic composite. To the best of tandem Knoevenagel condensation, larger-sized acetal exhibits poor yield of α,β-unsaturated dicyanides, and demonstrates pore-fitting-mediated size-selectivity.

FeCl3 Catalyzed Synthesis of cis‐Fused Reduced THC Analogues

AbstractStudies on a cycloisomerization reaction of 2‐prenylated‐2H‐pyrans towards cis‐fused tetrahydro‐6H‐benzo[c]chromene systems (reduced cis‐THC analogues) are reported. The transformation is catalyzed by iron chloride and proceeds with the formation of two new bonds and two stereocenters diastereoselectively. The same catalyst also promotes the formation of these products via a one‐pot tandem Knoevenagel condensation of 1,3‐cyclohexanediones and citral or farnesal aldehydes, followed by cycloisomerization establishing a direct assembly of this important scaffold.

One flask cascade approach to a complex pyrano[2,3-c]pyrazole-pyrazolone hybrid heterocyclic system and its initiatory neurobiological profiling.

A one-pot multicomponent approach towards a hybrid heterocyclic pyrano[2,3-c]pyrazole-pyrazolone framework involving tandem Knoevenagel condensation, sequential intermolecular 1,6-Michael addition, and 6-endo dig cyclization between diynones and pyrazolones, mediated by DBU, has been discovered. This process embodies several green and sustainable chemistry features. Preliminary bioactivity profiling of the new chemical entities indicates neuroprotective and AChE inhibitory activities.

Microwave-promoted Synthesis and Optoelectronic Properties of Ethoxycarbonyl-substituted Coumarin and Benzo[f]coumarin

Microwave-assisted potassium fluoride-catalyzed synthesis of coumarin derivatives via tandem Knoevenagel condensation and intramolecular cyclization was established under solvent-free conditions. Satisfactory product yields were obtained with 67.87 and 90.21% as the highest recorded yields for the target compounds 3a (ethyl 2-oxo-2H-chromen-3-carboxylate) and 3b (ethyl 2-oxo-2H-benzo[f]chromen-3-carboxylate), respectively. The changes in the optoelectronic properties of the synthesized coumarin derivatives relative to the parent coumarin (2H-chromen- 2-one) molecule were also characterized to study, to some degree, the structure-to-property relationship of the compounds. Generally, extending the π-conjugation at position-3 by adding the ethoxycarbonyl group and expanding the π-system of the coumarin molecule at position-f shifts the absorption maxima to longer wavelengths, decreases the HOMO-LUMO energy band gap, and increases the light absorptivity of the coumarin compound.

Urea hydrogen peroxide-initiated synthesis of pyranopyrazoles through oxidative coupling under base- and metal-free conditions by physical grinding method.

A novel multicomponent one-pot expeditious synthesis of highly functionalized and pharmaceutically fascinated pyranopyrazoles has been developed. This reaction occurs via tandem Knoevenagel condensation reaction of methyl aryl derivatives, 3-methyl pyrazolone and malononitrile in the presence of urea hydrogen peroxide under the physical grinding method. The present methodology offers several benefits such as available green and cheap starting materials, solvent-free, mild reaction conditions, high atom economy, eco-friendly standards, excellent yields and easy isolation of the products without column chromatographic separation.

NH4Cl/Zn powder: An efficient, chemoselective reducing catalyst for the microwave‐assisted synthesis of 2,3‐disubstituted quinolines via tandem Knoevenagel condensation

AbstractAn efficient, a hitherto unreported, sustainable, and environmentally friendly microwave‐assisted synthesis of 2,3‐disubstituted quinolines by reductive cyclization of 2‐nitrobenzaldehydes and various active methylene compounds via tandem Knoevenagel condensation promoted by an efficient eco‐friendly, chemoselective reducing catalyst ammonium chloride (NH4Cl) and zinc powder was developed. This present methodology is a mild, green, efficient, and environmentally benign process as it eliminates the harsh reaction conditions, non‐volatile solvents, relatively expensive reagents, high catalyst loading, and also provides a number of other benefits like fast synthesis, simple reaction set‐up, and good to the excellent yield of the products.

Guanine‐La complex supported onto SBA‐15: A novel efficient heterogeneous mesoporous nanocatalyst for one‐pot, multi‐component Tandem Knoevenagel condensation–Michael addition–cyclization Reactions

In this work, we present a simple, environmentally‐friendly and economical route for the preparation of a novel lanthanum (III) organometallic complex immobilized onto a highly stable mesoporous silica SBA‐15 (La‐guanine@SBA‐15) using an inexpensive and simple method and available materials. This mesoporous heterogenized complex was comprehensively characterized using FT‐IR, XRD, EDS, ICP, MAP, SEM, TGA and BET techniques. The catalytic activity of this mesoporous material was studied in one‐pot multi‐component tandem Knoevenagel condensation–Michael addition–cyclization reactions in order to prepare a series of benzo [a] pyrano [2, 3‐c] phenazine and 4,4′‐(arylmethylene)‐bis‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐ols) derivatives under green conditions. This catalyst exhibited highly recoverable and recyclable features in consecutive reaction runs. Besides, the products were obtained in high yields and short reaction times. In this sense, simple preparation of the catalyst from the commercially available materials, simple operation, high catalytic activity, short reaction times, high yields and the use of green reaction conditions in the mentioned organic synthesis are the most significant advantages of this protocol. In addition, this nanocatalyst was easily recovered, using simple filtration, and reused several times without significant loss of its catalytic efficiency. Moreover, the leaching, heterogeneity and stability of La‐guanine@SBA‐15 were studied by hot filtration test and ICP technique. Finally, stability of the catalyst after recycling was confirmed by SEM and FT‐IR techniques.

Application of $$\hbox {SiO}_{{2}}$$ SiO 2 nanoparticles as an efficient catalyst to develop syntheses of perimidines and tetraketones

In this paper, we explore the catalytic activity of $$\hbox {SiO}_{{2}}$$ nanoparticles (NPs) as an eco-friendly, efficient and reusable catalyst in the synthesis of 2,3-dihydro-1H-perimidines as well as tetraketones. For tetraketones syntheses, a simple tandem Knoevenagel condensation following Michael addition procedure is performed by the reaction between benzaldehydes and 5,5-dimethyl-1,3-cyclohexanediones under solvent-free condition using $$\hbox {SiO}_{{2}}$$ NPs as an efficient solid catalyst. In addition, for 2,3-dihydro-1H-perimidines syntheses, cyclocondensation of various aldehydes with 1,8-diaminonaphthalene is achieved under solvent-free condition using $$\hbox {SiO}_{{2}}$$ NPs as a catalyst at room temperature. The results showed catalytic enhancement in both synthetic procedures. In this work, 4-(2,3-dihydro-1H-perimidin-2-yl)benzonitrile and 2-(pyridin-4-yl)-2,3-dihydro-1H-perimidine are synthesized as new compounds. Also, reusability study of $$\hbox {SiO}_{{2}}$$ NPs was done to ensure its applicability as a recycled catalyst in this work. The catalytic activity of $$\hbox {SiO}_{{2}}$$ nanoparticles (NPs) as an eco-friendly, efficient and reusable catalyst in the synthesis of 2,3-dihydro-1H-perimidines as well as tetraketones is explored. For tetraketones syntheses, a simple tandem Knoevenagel condensation following Michael addition procedure is performed by the reaction between benzaldehydes and 5,5-dimethyl-1,3-cyclohexanediones under solvent-free condition using $$\hbox {SiO}_{{2}}$$ NPs as an efficient solid catalyst.

MOF‐promoted Three‐component Synthesis of Functionalized Pyrano[3,2‐c]chromen under Mild Conditions

A convenient and efficient route for synthesis of various derivatives of 3‐benzoyl‐4‐phenyl‐2‐(trifluoromethyl)pyrano[3,2‐c]chromen‐5(4H)‐one has been used via tandem Knoevenagel condensation–Michael addition and intramolecular cyclization sequence. These products have been synthesized in the presence of catalytic amount of metal–organic framework (MOF) and potassium carbonate as one‐pot, three‐component reaction. MOF catalyst has been separated easily with external magnet, and high purity of products has been obtained after washing with ethanol. This protocol has advantages of simplicity, mild condition, and high yield. More importantly, MOF has been easily recycled for three times.

Synthesis of indole-cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process.

The one-pot four-component reaction of 3-(1H-indol-3-yl)-3-oxopropanenitriles, aromatic aldehydes, cycloalkanones and ammonium acetate occurred via a six-step tandem Knoevenagel condensation–nucleophilic addition to carbonyl–Michael addition–N-cyclization–elimination–air oxidation sequence to afford structurally intriguing indole–cycloalkyl[b]pyridine-3-carbonitrile hybrid heterocycles in excellent yields.

Copper-Catalyzed Cascade Synthesis of 2-Aryl-3-cyanobenzofuran and Dibenzo[ b, f]oxepine-10-carbonitrile Derivatives.

The copper-catalyzed reaction of aryl aldehydes with 2-iodobenzylcyanides afforded 2-aryl-3-cyanobenzofurans in isolated yields of up to 74% in a cascade manner, which involves Knoevenagel condensation, aryl hydroxylation, oxa-Michael addition, and aromatization reactions. Conversely, 2-halo benzaldehydes as reacting partners with 2-iodobenzylcyanide regioselectively furnished dibenzo[ b,f]oxepine-10-carbonitrile derivatives up to 85% isolated yields via tandem Knoevenagel condensation, aryl hydroxylation, and Ullmann coupling reactions.

Nickel‐Catalyzed Tandem Knoevenagel Condensation and Intramolecular Direct Arylation: Synthesis of Pyrazolo[5,1‐a]‐isoquinoline Derivatives

AbstractA simple and efficient method for the synthesis of pyrazolo[5,1‐a]isoquinoline derivatives has been developed using the nickel‐catalyzed reaction of 1‐aryl‐2‐(1H‐pyrazol‐1‐yl)ethan‐1‐ones and 2‐bromo aldehydes. The overall transformation involves tandem Knoevenagel condensation and intramolecular direct arylation via activation of the C5−H bond of the pyrazole ring. A series of 27 drug‐like aroyl−substituted pyrazolo[5,1‐a]isoquinolines has been synthesized in moderate to good yields.magnified image

A novel bifunctional Pd–ZIF-8/rGO catalyst with spatially separated active sites for the tandem Knoevenagel condensation–reduction reaction

A novel bifunctional catalyst for the Knoevenagel condensation–reduction tandem reaction was prepared by immobilizing ZIF-8 and Pd on GO, respectively.

A new strategy for synthesis of 9-benzoyl-4-methylpyrano[2,3-f]chromene-2,8-dione using L-proline as a novel and efficient catalyst

We report the high yield synthesis of novel 9-benzoyl-4-methylpyrano[2,3-f]chromene-2,8-dione derivatives obtained by the reaction of 8-formyl-7-hydroxy-4-methylcoumarin with various active methylene compounds. A mechanism of the tandem Knoevenagel condensation and cyclisation reaction is proposed. Structures of all compounds were elucidated on the basis of 1H and 13C NMR, and mass spectrometry, and elemental analysis.

Tandem Knoevenagel Condensation and Intramolecular Cycloaddition Reactions of 2-Azidobenzaldehydes with 2-Cyanoacetamides in the Synthesis of 4-Thiocarbamoyltetrazolo-[1,5-a]Quinolines

The reaction of 2-azidobenzaldehydes with 2-thioamides of cyanoacetic acid proceeds without a solvent and base at 80–90°C selectively by one of the possible routes to form tetrazolo[1,5-a]quinolines. The proposed mechanism of the reaction involves the Knoevenagel condensation and subsequent intramolecular [3+2] cycloaddition of the azide group at the C≡N bond of an intermediate acrylonitrile.

ChemInform Abstract: Copper‐Catalyzed Synthesis of Quinoline Derivatives via Tandem Knoevenagel Condensation, Amination and Cyclization.

AbstractKnoevenagel condensation of 2‐bromobenzaldehydes with active methylene nitriles followed by copper‐catalyzed reductive amination and intramolecular cyclization affords 2‐aminoquinolines and 2‐arylquinoline‐3‐carbonitriles regioselectively.

Postfunctionalized Porous Polymeric Aromatic Frameworks with an Organocatalyst and a Transition Metal Catalyst for Tandem Condensation–Hydrogenation Reactions

Novel heterogenized bifunctional catalysts were prepared combining a rhodium complex with a pyrrolidine on porous polymeric aromatic frameworks (PAFs) based on tetraphenyladamantane and tetraphenylmethane subunits. These new systems catalyze efficiently tandem Knoevenagel condensation and hydrogenation of the resulting olefin. These tandem reactions represent an easy and selective methodology for monoalkylation of methylene active compounds from aldehydes. The obtained bifunctional PAFs exhibit high activity and excellent stability in the cascade reactions and can be recycled up to ten times in a productive process.

Copper-catalyzed synthesis of quinoline derivatives via tandem Knoevenagel condensation, amination and cyclization

A novel regioselective synthesis of 2-aminoquinolines and 2-arylquinoline-3-carbonitriles is described via copper-mediated tandem reaction.

ChemInform Abstract: One‐Pot, Three‐Component Approach to the Synthesis of 3,4,5‐Trisubstituted Pyrazoles.

AbstractThe mechanistically novel one‐pot, three‐component coupling of aldehydes, dicarbonyls, and diazo compounds proceeds by a tandem Knoevenagel condensation, 1,3‐dipolar cycloaddition, and transition metal‐free oxidative aromatization reaction sequence involving the cleavage of an acetyl group for pyrazole formation.

One-pot, three-component approach to the synthesis of 3,4,5-trisubstituted pyrazoles.

An operationally simple and high yielding protocol for the synthesis of polyfunctional pyrazoles has been developed through one-pot, three-component coupling of aldehydes, 1,3-dicarbonyls, and diazo compounds as well as tosyl hydrazones. The reaction proceeds through a tandem Knoevenagel condensation, 1,3-dipolar cycloaddition, and transition metal-free oxidative aromatization reaction sequence utilizing molecular oxygen as a green oxidant. The scope of the reaction was studied by varying the aldehyde, 1,3-dicarbonyl, and diazo component individually.