Cellulose sulphuric acid as a biodegradable and reusable catalyst for the Knoevenagel condensation

A green, mild and efficient method for Knoevenagel condensation of 3-formylchromone/2-chlroquinoline-3-carbaldehyde with active methylene compounds such as Meldrum’s acid/ethyl cyanoacetate using biosupported cellulose sulphuric acid (CSA) in the solid-state by grinding under solvent-free condition has been developed. This method provides several advantages including environmental friendliness, shor t reaction times, high yields and a simple work-up procedure. Moreover, the CSA was successfully reused for four cycles without significant loss of activity.     

微波促进3-甲酰基色酮与活性亚甲基的缩合反应

微波辐射下,3-甲酰基色酮与活性亚甲基化合物缩合反应,合成了3个新的3-甲酰基色酮衍生物,收率80％～92％,其结构经^1HNMR和IR表征。     

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.     

Novel benzopyranopyridine derivatives of 2-amino-3-formylchromone

Enol lactones such as 4-hydroxy-6-methyl-2H-pyran-2-one (triacetic acid lactone, TAL) and 4-hydroxycoumarin when treated with 2-amino-3-formylchromone under basic conditions afforded 3-acetoacetyl benzopyranopyridones and benzopyranopyridines, respectively. A series of pyrazole derivatives was prepared by the reaction of 3-acetoacetyl benzopyranopyridones with different hydrazines. All compounds were characterised on the basis of spectral data and their antibacterial activity evaluated.     

Preparation of 5-Cyano-4,6-dimethyl-2H-pyran-2-one and 3-Cyano-5-methoxy-4-methyl-5H-furan-2-one via a One-Pot,Domino-Knoevenagel Process

5-Cyano-4,6-dimethyl-2H-pyran-2-one (1) has been prepared via a simple one-pot domino-Knoevenagel reaction starting from ethyl acetoacetate (2) and cyanoacetone (3). Similarly, a new racemic 3-cyano-5-methoxy-4-methyl-5H-furan-2-one (7) has been prepared from 1,1-dimethoxyacetone (6) and cyanoacetic acid (4). The new alkylidene derivatives (Z/E)-ethyl-4-cyano-3-methylbut-3-enoate (5), (Z/E)-ethyl 5-amino-4-cyano-3-methyl-5-oxopent-3-enoate (9), and (2,2-dimethoxy-1-methylethylidene)malononitrile (11) have been prepared via the Knoevenagel reactions. The easy access to these new compounds in good yields shows that ammonium acetate/acetic acid–catalyzed Knoevenagel reactions and domino-Knoevenagel reactions have a broad scope of application.     

Synthetic and Structural Studies on Novel 4,3′-Bicoumarins

Abstract

A series of directly linked 4-3′ bicoumarins have been synthesized by both Knoevenagel and Perkin reactions. This single-step transformation was accomplished by the reaction of coumarin-4-acetates with substituted salicylaldehydes in presence of piperidine using ethanol as solvent and by the reaction of coumarin-4-acetic acids with substituted salicylaldehydes in the presence of sodium hydride in acetic anhydride. Greater yields have been obtained in the sodium hydride and acetic anhydride condition. An intermediate chalcone with an ortho-hydroxyl group, which is a precursor for lactone formation, has been isolated and its structure has been confirmed by x-ray analysis. The nonplanar S-cis arrangement of two C4-C3’ double bonds has been confirmed by nuclear Overhauser spectroscopy (NOE) and x-ray studies. The UV-fluorescence studies support the formation of a conjugated bicoumarin system.     

L-Proline-Catalyzed Knoevenagel Condensation: A Facile,Green Synthesis of (E)-Ethyl 2-Cyano-3-(1H-indol-3-yl)acrylates and (E)-3-(1H-Indol-3-yl)acrylonitriles

L-Proline has been utilized as a novel and ecofriendly catalyst in ethanol medium for the Knoevenagel condensation of indole-3-carboxyaldehydes and their N-methyl derivatives 1(a–e) and 4(a–e) with the active methylene compound, ethyl cyanoacetate (2) to afford substituted (E)-ethyl 2-cyano-3-(1H-indol-3-yl)acrylates 3(a–e) and 5(a–e) respectively. These products were reacted with dimethyl sulfate in the presence of PEG-600 as an efficient and green solvent to afford the corresponding N-mthylated derivatives 5(a–e). These Knoevenagel products react with 5% NaOH, yielding (E)-3-(1H-indol-3-yl)acrylonitriles 6(a–e) and 7(a–e).     

Synthesis of 3-(3-Alkyl-5-thioxo-1H-4,5-dihydro-1,2,4-triazol-4-yl)aminocarbonylchromones

A series of 3-(3-alkyl-5-thioxo-1H-4,5-dihydro-1,2,4-triazol-4-yl)aminocarbonylchromones has been prepared by oxidation of 3-formylchromone with Jones' reagent followed by reaction with 3-alkyl-4-amino-4,5-dihydro-1,2,4-triazole-5(1H)-thione in the presence of POCl³. The structures of the compounds were confirmed by IR, LC-MS, and ¹H NMR spectra and elemental analyses.     

Synthesis and transformations of (imidazolylimino)thiazolidinones

The reaction of ethyl 5-phenylthioureido-3H-imidazole-4-carboxylate with bromoacetic acid afforded (imidazolylimino)thiazolidinones, which were transformed into the corresponding 5-arylidene-4-thiazolidinones by the reactions with aldehydes. Under the conditions of the Knoevenagel reaction, the thiazolidine ring in derivatives of 4-(4-oxothiazolidin-2-ylideneamino)-3H-imidazole-4-carboxamides was opened to form substituted guanidines.     

Microwave Assisted Green Multicomponent Synthesis of Novel bis(2‐Amino‐tetrahydro‐4H‐chromene‐3‐carbonitrile) Derivatives Using Chitosan as Eco‐friendly Basic Catalyst

A simple, efficient, and eco‐friendly procedure has been developed for the synthesis of bis(4H‐chromene‐3‐carbonitrile) derivatives using chitosan as catalyst under microwave‐assisted reaction conditions. For the sake of comparison, the reaction was also carried out under conventional heating in the presence of each of chitosan and piperidine as basic catalysts.     

The Convenient Synthesis of 11‐Methyl‐3,8‐disubstituted‐12‐aryl‐3,4,7,8,9,12‐hexahydro‐1H‐chromeno[2,3‐b]quinoline‐1,10(2H)‐dione Derivatives

The 2‐arylidene‐3‐oxobutanenitrile derivatives 2 were prepared by the Knoevenagel condensation between aldehydes and 3‐oxobutanenitrile 1 , which was obtained by acid hydrolysis of β‐aminocrotononitrile. 3‐Acetyl‐2‐amino‐4H‐chromen‐5(6H)‐one derivatives 3 were synthesized by reaction of 2‐arylidene‐3‐oxobutanenitrile 2 and 5‐substituted‐1,3‐cyclohexanedione in ethylene glycol. The 11‐methyl‐3,8‐disubstituted‐12‐aryl‐3,4,7,8,9,12‐hexahydro‐1H‐chromeno[2,3‐b]quinoline‐1,10(2H)‐dione derivatives 4 were obtained by Friedländer reaction of compounds 3 with 5‐substituted‐1,3‐cyclohexanedione, using p‐toluenesulfonic acid monohydrate as catalyst. The structures of all novel compounds were characterized by elemental analysis, IR, MS, and ¹H NMR spectra. The crystal and molecular structure of compound 4f has been determined by single crystal XRD analysis.     

Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone

The review is focused on recent developments of chemistry of synthetic analogs of natural compounds, isoflavone and homoisoflavone. The possible synthetic strategies to access heterocyclic analogs of these compounds starting from readily available 3-formylchromone and its derivatives (3-cyanochromone, 2-amino-3-formylchromone) and products of its condensation with simplest C- and N-nucleophiles are discussed. The structural features of the reaction products that depend on the nature of the reaction medium, structure of the starting compounds, and reagent ratio are considered. Particular attention is given to the application of the modern strategies of organic synthesis, namely green chemistry approaches, click reactions, domino reactions, etc. Examples of compounds of this group most promising for clinical application due to wide and pronounced pharmacological effects are given.

     

One-Pot Wittig and Knoevenagel Reactions in Ionic Liquid as Convenient Methods for the Synthesis of Coumarin Derivatives

Efficient synthesis of a variety of 3-substituted coumarins via NaOMe-catalyzed Knoevenagel condensation and one-pot preparation of 3,4-unsubstituted coumarins in the presence of NaOMe via Wittig reaction in room-temperature ionic liquids are described. Knoevenagel condensation of 2-hydroxybenzaldehyde with dimethyl- and diethylmalonate was performed with excellent yields in room-temperature ionic liquids. Although diethyl- and dimethylchloromalonates were mostly recovered unchanged in Knoevenagel condensation, higher conversions were observed via Wittig reaction of these compounds with 2-hydroxybenzaldehyde derivatives and triphenylphosphine. Other 2-hydroxybenzaldehyde derivatives, methyl- and ethylchloroacetates, were reacted in ionic liquids to afford simple coumarins in good yields. These reactions widen the applicability of ionic liquid in organic synthesis.     

L-proline/urea catalyzed,novel, and eco-friendly synthesis of coumarin substituted-3-indoloxanthenes

A green and eco-friendly synthesis of coumarin substituted-3-indoloxanthenes 4(a-l) has been developed using urea/L-proline as simple catalyst. Two efficient methods have been described for the synthesis of these 3-indoloxanthene derivatives. In the first method, Knoevenagel condensation, then Pinner cyclisation followed by 1,4 addition between 4-hydroxy-1-methyl-2-oxo-1,2-dihydrocoumarin-3-carbaldehyde 1(a-b) , with cyclohexane-1,3-dione (2) and indole 3(a-f) using of L-proline as catalyst was described. In the second method, urea/thiourea catalyzes the same reaction at 100°C for 10 minutes to afford the title compounds 4(a-l) . These two protocols involve eco-friendly and inexpensive catalysts, give excellent yields of the clean products without the need of column chromatography for their isolation or purification.     

Synthesis of fused uracils: pyrano[2,3-d]pyrimidines and 1,4-bis(pyrano[2,3-d]pyrimidinyl)benzenes by domino Knoevenagel/Diels-Alder reactions

Abstract  

Knoevenagel condensation of barbituric acids with aromatic aldehydes containing one or two formyl groups was carried out. 5-Arylidenebarbituric acids underwent smooth hetero-Diels-Alder (HDA) reactions with enol ethers to afford cis and trans diastereoisomers of pyrano[2,3-d]pyrimidine-2,4-diones and 5,5′-(1,4-phenylene)bis[2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione] derivatives in excellent yields (75–88 %). Syntheses were realized by Knoevenagel condensation and HDA reaction in four different reaction conditions: Knoevenagel condensation in water and Diels-Alder reaction in methylene chloride solution, Knoevenagel condensation in water and Diels-Alder reaction without solvent, three-component one-pot reaction in methylene chloride solution, or three-component one-pot reaction in water. All reactions were carried out without catalyst at room temperature. The reactions of malononitrile with Knoevenagel condensation products of barbituric acids and heteroaromatic aldehydes or terephthalaldehyde were examined and did not provide corresponding pyranopyrimidines.     

A three component one-pot synthesis of N-amino-2-pyridone derivatives catalyzed by KF-Al2O3

Synthesis of 1,6-diamino-4-phenyl-3,5-dicyano-2-pyridone derivatives via a one-pot, three-component reaction of aryl aldehydes, malononitrile, and cyanoacetic hydrazide at room temperature using KF-Al₂O₃ as a recyclable catalyst have been developed. The reaction proceeds through the initial Knoevenagel condensation between aldehyde and malononitrile in the presence of KF-Al₂O₃ to form the benzylidene derivative which then undergoes Michael addition with cyanoacetic hydrazide followed by intramolecular cyclization of the resulting intermediate to produce the N-amino-2-pyridones in good to excellent yields. The structure of the synthesized compounds were characterized and established on the basis of their spectral data analysis and single-crystal XRD analysis.     

Chemo- and diastereoselective synthesis of new oxa[3.3.3]propellane via a domino cascade four-component reaction based on diketene

A highly convergent, eco-friendly and straightforward synthesis of new O-fused heterocycles, functionalized indeno[1,2-b]furan derivatives was successfully accomplished through a one-pot four-component cascade reaction involving, ninhydrin, malononitrile, diketene and various primary amines in the presence of a catalytic quantity of triethylamine in ethanol at ambient temperature, in one pot fashion. This new efficient cascade reaction generates two rings by the simultaneous construction of C-N (one), C-O (two) and C-C (two) multiple bonds, presumably through a sequence of Knoevenagel reaction/Michael addition/intramolecular O-cyclization and imine-enamine/keto-enol tautomerization. The merits of this protocol are highlighted as utilization of inexpensive commercially accessible starting materials, operational simplicity, atom economy, clean reaction profile, simple work-up procedure being conducted at ambient temperature in relatively short reaction times, preventing chromatographic purification, giving excellent yields, and tolerance to a wide variety of functional groups.     

One pot synthesis of new benzopyranopyridines via Friedlander condensation

A facile, green synthetic route to new benzopyrano [2,3-b] pyridines in excellent yield via Friedlander condensation has been developed by the reaction of 2-amino-3-formylchromone 1a-b and cyclic active methylene compounds 2a-e in the presence of Zn(l-proline)₂ as an efficient, stable, and inexpensive Lewis acid catalyst in water. The present methodology offers several advantages such as shorter reaction time, mild reaction conditions, simple operational procedure, recyclable catalyst, and safe to the environment.     

Choline chloride based eutectic solvent for the efficient synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives via multicomponent reaction under mild conditions

Synthesis of 2-amino-4H-chromen-4-ylphosphonate derivatives has been accomplished by the one-pot three-component reaction of salicylaldehyde, malononitrile/ethylcyanoacetate and dialkyl phosphites in the presence of reusable deep eutectic solvent (DES) under mild conditions. The advantages of this method are mild reaction conditions, simple work-up procedure, use of DES as a green solvent and an economical protocol for the preparation of important biologically active phosphorus-containing compounds.     

Indium Trichloride (InCl3) Catalyzed Synthesis of Fused 7‐Azaindole Derivatives Using Domino Knoevenagel‐Michael Reaction

An efficient and high yielding methodology developed for the synthesis of fused 7‐azaindole derivatives via one pot multicomponent assembly process of cyclic 1,3‐dicarbonyls with substituted aldehydes and 5‐amino‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitrile. The transformation occurs via domino Knoevenagel‐ Michael reaction followed by intramolecular cyclization in the presence of catalytic amount of InCl₃ (10 mol %). Mild reaction conditions, easy isolation of products, and good to excellent yields in a shorter period of time are the silent features of present methodology. Structures of all the newly prepared compounds have been corroborated by various spectroscopic methods.