Synthesis and Reactions of the Novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde

The novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde ( 2 ) was efficiently synthesized from Vilsmeier–Haack formylation of 3‐(1‐ethy1‐4‐hydroxy‐2‐oxo‐(1H)‐quinolin‐3‐yl)‐3‐oxopropanoic acid ( 1 ). The aldehyde 2 was allowed to react with some nitrogen nucleophiles producing a variety of hydrazones 3 – 7 . Reaction of aldehyde 2 with hydrazine hydrate and hydroxylamine hydrochloride afforded pyrazole and isoxazole annulated pyrano[3,2‐c]quinoline‐2,5(6H)‐dione, respectively. The reactivity of aldehyde 2 was examined toward some active methylene nitrile, namely, malononitrile, ethyl cyanoacetate, and cyanoacetamide leading to 2‐iminopyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines 10 – 12 , respectively. Also, some novel pyrazolo[4″,3″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines ( 13 , 14 ) and thiazolo[5″,4″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines ( 15 , 16 ) were synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

One‐pot Two‐step Reaction for Synthesis of Poly‐substituted Pyrano[3,2‐c]pyridones and Spiro[indoline‐3,4′‐pyrano[3,2‐c]pyridine]‐2,5′(6′H)‐diones in Water

An efficient four‐component approach for the synthesis poly‐substituted pyrano[3,2‐c]pyridones and spiro[indoline‐3,4′‐pyrano[3,2‐c]pyridine]‐2,5′(6′H)‐diones in water has been established. During the reaction, the products were readily achieved through one‐pot two‐step reaction using solid acid as catalyst. The advantages of atom and step economy, the recyclability of heterogeneous solid acid catalyst, easy workup procedure, and the wide scope of substrates make the reaction a powerful tool for assembling pyrano[3,2‐c]pyridone skeletons of chemical and medical interest.     

Fast Efficient and General PASE Approach to Medicinally Relevant 4H,5H‐Pyrano‐[4,3‐b]pyran‐5‐one and 4,6‐Dihydro‐5H‐pyrano‐[3,2‐c]pyridine‐5‐one Scaffolds

The general ‘on‐solvent’ PASE approach was found to be medicinally relevant for 4H,5H‐pyrano[4,3‐b]pyran‐5‐one and 4,6‐dihydro‐5H‐pyrano[3,2‐c]pyridine‐5‐one scaffolds. Ammonium acetate‐catalyzed multicomponent reaction of aldehydes and two different C–H acids in the presence of small amounts of EtOH results in fast (3 – 15 min) and efficient formation of scaffolds, promising for many diverse oriented medical applications.     

Synthesis of Pyrano[3,2‐c]quinoline‐3‐carboxaldehyde and 3‐(Ethoxymethylene)‐pyrano[3,2‐c]quinolinone and Their Chemical Behavior toward Some Nitrogen and Carbon Nucleophiles

Synthesis of novel 3‐(ethoxymethylene)‐pyrano[3,2‐c]quinolinone and pyrano[3,2‐c]quinoline‐3‐carboxaldehyde was accomplished efficiently via a simple method. These two scaffolds were used as precursors to afford new biologically interesting products in good yield and short reaction times. The chemical reactivity of ethoxy methylene 2 and carboxaldehyde 3 toward different nucleophilic reagents was studied. Structures of the new synthesized compounds were elucidated by their analytical and spectral data.     

Efficient One‐Pot Syntheses of 7‐Alkyl‐6H,7H‐naphtho[1,2:5,6]pyrano‐[3,2‐c]chromen‐6‐ones by 1‐Methyl‐3‐(2‐(sulfooxy)ethyl)‐1H‐imidazol‐3‐ium Chloride

An efficient synthesis of 7‐alkyl‐6H,7H‐naphtho‐[10,20:5,6]pyrano[3,2‐c]chromen‐6‐ones by three‐component condensation reaction of β‐naphthol, aromatic aldehydes, and 4‐hydroxycoumarin catalyzed by 1‐methyl‐3‐(2‐(sulfooxy)ethyl)‐1H‐imidazol‐3‐ium chloride is reported in good to excellent yields and short reaction times.     

Synthesis of Some Novel Heteroannulated Pyrano[3,2‐c]quinoline‐2,5(6H)‐diones

6‐Butyl‐3‐((dimethylamino)methylene)pyrano[3,2‐c]quinolinone and 6‐butyl pyrano[3,2‐c]quinolone‐3‐carbonitrile were efficiently synthesized in good yield. These two new precursors were used to obtain some novel heteroannulated pyrano[3,2‐c]quinolone derivatives from heterocyclization reactions with various binucleophiles. These heteroannulation reactions afforded novel heterocyclic systems fused to the pyranoquinolinone at face c, such as pyrazole, pyrimidine, pyridine, and pyrazolopyranone.     

Zr(HSO4)4‐catalyzed one‐pot three‐component synthesis of 7‐alkyl‐6H,7H‐naphtho[1′,2′:5,6]pyrano[3,2‐c]chromen‐6‐ones

A new, one‐pot, simple thermally efficient and solvent‐free method for the preparation of 7‐alkyl‐6H,7H‐naphtho[1′,2′:5,6]pyrano[3,2‐c]chromen‐6‐ones by condensation of β‐naphthol, aromatic aldehydes, and 4‐hydroxycoumarin using Zr(HSO₄)₄ as a safe and efficient catalyst is described. This method has the advantages of high yields, a cleaner reaction, simple methodology, short reaction times, easy workup, and greener conditions. J. Heterocyclic Chem., (2011).     

Synthesis of 3‐Acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐one Derivatives

The cyclization of aryl ketone anilides 3 with diethyl malonate to affords 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]‐pyridin‐2,5‐diones 4 in good yields. 3‐Acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 are obtained by ring‐opening reaction of 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]‐pyridin‐2,5‐diones 4 in the presence of 1,2‐diethylene glycol. The reaction of 3‐acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 with hydroxylamine hydrochloride produces 4‐hydroxy‐3‐[N‐hydroxyethanimidoyl]‐1‐phenylpyridin‐2(1H)‐ones 6 from which 3‐alkyloxyiminoacetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 7 are obtained by reacting with alkyl bromides or iodides in the presence of anhydrous potassium carbonate with moderate yields. The similar compounds can be synthesized on refluxing 3‐acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 with substituted hydroxylamine hydrochloride in the presence of sodium bicarbonate with good yields. Most of the synthesized compounds are characterized by IR and NMR spectroscopic methods.     

Polypyrrole/Fe3O4/CNT as a recyclable and highly efficient catalyst for one‐pot three‐component synthesis of pyran derivatives

Polypyrrole (PPY)/Fe₃O₄/CNT has been synthesized and characterized by FT‐IR, TEM and SEM techniques and its catalytic activity has been evaluated in the synthesis of several series of pyran derivatives. Tetrahydrobenzo[b]pyranes, 4H‐pyran‐3‐carboxylates, 4H,5H‐pyrano[3,2‐c]chromenes and dihydropyrano[2,3‐c]pyrazoles have been successfully prepared from one‐pot three‐component condensation of aldehyde, malononitrile and active methylene‐containing compounds (dimedone /ethyl acetoacetate/4‐hydroxycoumarin/3‐methyl‐2‐pyrazoline‐5‐one) using PPY/Fe₃O₄/CNT as a new and reusable heterogeneous catalyst. The present method offer several advantages such as; high yields of products, short reaction times, easy work‐up procedure and easy separation of the catalyst from the reaction mixture due to its magnetic character. Furthermore, chemoselective synthesis of bis‐benzo[b]pyran from terephthalaldehyde can be achieved by this method.     

Synthesis of Ethyl 2‐Amino‐4‐benzoyl‐5‐oxo‐5,6‐dihydro‐4H‐pyrano[3,2‐c]quinoline‐3‐carboxylates by a One‐pot,Three‐Component Reaction in the Presence of TPAB

In this research, in order to synthesize a series of ethyl 2‐amino‐4‐benzoyl‐5‐oxo‐5,6‐dihydro‐4H‐pyrano[3,2‐c]quinoline‐3‐carboxylates, a green and an efficient method is proposed through one‐pot three‐component reaction of substituted arylglyoxals, ethyl cyanoacetate, and 4‐hydroxyquinolin‐2(1H)‐one in the presence of terapropylammonium bromide as a catalyst in good yields. All synthesized new substances were characterized by FTIR, ¹H‐NMR, and ¹³C‐NMR spectral data and elemental analysis.     

Synthesis of Acetyl and Iodo Derivatives of 4‐Hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]pyridine‐2,5‐diones and 4‐Hydroxy‐1‐phenylpyridin‐2(1H)‐ones

A simple and efficient method has been described for the synthesis of acetyl and iodo derivatives of 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 1 and 4‐hydroxy‐1‐phenylpyridin‐2(1H )‐ones 5 . Compounds 1 with phenyl and alkyl substituent at C(7) and C(8), respectively, can be easily acetylated by refluxing in a mixture of acetic acid and polyphosphoric acid to give 3‐acetyl‐4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 2 in excellent yields. Compounds 1 and 5 can be iodinated with iodine and anhydrous sodium carbonate in boiling dioxane to give 4‐hydroxy‐3‐iodo‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 3 and 4‐hydroxy‐3‐iodo‐1‐phenylpyridin‐2(1H )‐ones 6 , respectively, in good yields. The structures were confirmed using infrared, nuclear magnetic resonance , and elemental analysis.     

1,8‐Diazabicyclo[5.4.0]undec‐7‐ene: A Highly Efficient Catalyst for One‐Pot Synthesis of Substituted Tetrahydro‐4H‐chromenes,Tetrahydro[b]pyrans,Pyrano[d]pyrimidines,and 4H‐Pyrans in Aqueous Medium

We have reported 1,8‐diazabicyclo[5.4.0]undec‐7‐ene catalyzed one‐pot synthesis of tetrahydro‐4H‐chromenes, tetrahydro[b]pyrans, pyrano[d]pyrimidines and 4H‐pyrans from aldehydes, active methylene compounds malononitrile/ethyl cyanocacetate and activated C–H acids such as dimedone, 1,3‐cyclohexanedione, 1,3‐cyclopentanedione, 1,3‐dimethylbarbituric acid, and ethyl acetoacetate in water under reflux. The attractive features of this process are mild reaction conditions, reusability of the reaction media, short reaction times, easy isolation of products, and excellent yields. Copyright © 2013 HeteroCorporation     

Reactions of alkyl (z)‐2‐[(E)‐2‐ethoxycarbonyl‐2‐(2‐pyridinyl)‐ethenyl]amino‐3‐dimethylaminopropenoates with C‐ and N‐nucleophiles. the synthesis of fused pyranones,pyridinones and pyrimidinones

Alkyl 2‐[2‐ethoxycarbonyl‐2‐(2‐pyridinyl)ethenyl]amino‐3‐dimethylaminopropenoates 3 and 4 were transformed with C‐and N‐nucleophiles into β‐heteroaryl‐α,β‐didehydro‐α‐amino acid derivatives 13 ‐ 16 , substituted 3‐amino‐4H‐quinolizin‐4‐one 17, 2H,5H‐benzo[b]pyran‐2,5‐dione 18 and 19 , 2H,5H‐pyrano[4,3‐b]pyran‐2,5‐dione 20 , 2H,5H‐pyrano[3,2‐c]benzo[b]pyran‐2,5‐dione 21 , 2H‐1‐benzopyran‐2‐one 22 and 24 , pyrido[l,2‐a]pyrimidin‐4‐one 31–34 and 39 derivatives, and N‐heteroaryl‐1H‐imidazole‐4‐carboxylates 37 and 38 .     

4‐Hydroxy‐1‐phenylquinolin‐2(1H)‐one in One‐pot Synthesis of Pyrimidoquinolines and Related Compounds under Microwave Irradiation and Conventional Conditions

Biginelli condensation reactions of 4‐hydroxy‐1‐phenylquinolin‐2(1H)‐one, aryl aldehydes and urea, or thiourea, 5‐amino‐1H‐1,2,4‐triazole, or 2‐amine‐1H‐benzimidazole ( 9 ) under microwave irradiation afforded the corresponding pyrimido[5,4‐c]quinolin‐5‐one derivatives in high yields. One‐pot synthesis of 2H‐pyrano[3,2‐c]quinolines is also reported.     

An Efficient and Facile Synthesis of tert‐Butyl 2‐(Methylamino)‐3‐nitro‐5‐oxo‐4‐aryl‐7,8‐dihydro‐4H‐pyrano[3,2‐c]pyridine‐6(5H)‐carboxylate derivatives in [BMIM]BF4

In this research, we have developed an efficient three‐component reaction for the synthesis of pyrano[3,2‐c]pyridine derivatives from the reaction of aromatic aldehydes, tert‐butyl 2,4‐dioxopiperidine‐1‐carboxylate, and N‐methyl‐1‐(methylthio)‐2‐nitroethylen‐1‐amine in [BMIM]BF₄ medium. The advantages of this method were readily available starting materials, simple reaction conditions, and satisfactory yields.     

A Convenient Synthesis of 2H‐Pyran‐2‐ones,Fused Pyran‐2‐ones,and Pyridones Bearing a Thiazole Moiety

The versatile enaminonitrile, 2‐cyano‐3‐(dimethylamino)‐N‐(4‐phenylthiazol‐2‐yl)‐acrylamide ( 2 ), reacts with some C,O‐binucleophiles (acetylacetone and dimedone) in refluxing acetic acid to afford the pyranone 4 , the chromene 6 derivatives, and with C,N‐binucleophiles (2‐(benzothiazol‐2‐yl)acetonitrile and 2‐(1H‐benzimidazol‐2‐yl)acetonitrile) to afford the respective 1H‐pyrido[2,1‐b]benzothiazole 8 and pyrido[1,2‐a]benzimidazole 10 derivatives. Similar treatment of 2 with phenol, resorcinol, α‐naphthol and β‐naphthol in boiling acetic acid gave the coumarin derivatives 12 , 14 , 16 , and 18 , respectively. The utility of enaminonitrile 2 for the synthesis of 6H‐pyrano[3,2‐d]isoxazole 20 , pyrano[2,3‐c]pyrazole 22 , and pyrano[2,3‐d]pyrimidine 24 derivatives was also explored via its reaction with 3‐phenylisoxazol‐5(4H)‐one, 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one, and barbituric acid, respectively. The mechanistic aspects for the formation of the new compounds were also discussed.     

Synthesis of Heteroannulated Chromeno[2,3‐b]Pyridines: DBU Catalyzed Reactions of 2‐Amino‐6‐methylchromone‐3‐Carboxaldehyde with Some Heterocyclic Enols and Enamines

New series of heteroannulated chromeno[2,3‐b]pyridines were easily and efficiently synthesized from DBU‐catalyzed condensation of 2‐amino‐6‐methylchromone‐3‐carboxaldehyde with a variety of heterocyclic enols and enamines, namely, 4‐hydroxycoumarin, 4‐hydroxy‐1‐methylquinolin‐2(1H)‐one, 2‐hydroxy‐4H‐pyrido[1,2‐a]pyrimidin‐4‐one, 4‐hydroxy‐2H‐pyrano[3,2‐c]quinoline‐2,5(6H)‐dione, 4(6)‐aminouracil and 5‐amino‐3‐methyl‐1H‐pyrazole. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Synthesis of Novel Spiro Pyrano[2,3‐d]thiazolo[3,2‐a]pyrimidine via 1,3‐Dipolar Cycloaddition of Azomethine Ylide

The reaction involving 4‐phenyl‐octahydro‐pyrano[2,3‐d]pyrimidine‐2‐thione, ethyl chloroacetate and the appropriate aromatic aldehyde yielded 2‐arylmethylidene‐5‐phenyl‐5a,7,8,9a‐tetrahydro‐5H,6H‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidin‐3(2H)‐ones. The 1,3‐dipolar cycloaddition of 2‐arylmethylidene‐5‐phenyl‐5a,7,8,9a‐tetrahydro‐5H,6H‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidin‐3(2H)‐ones with azomethine ylide generated by a decarboxylative route from sarcosine and acenaphthenequinone afforded 4′‐aryl‐1′‐methyl‐5″‐phenyl‐5a″,7″,8″,9a″‐tetrahydro‐2H,5″H,6″H‐dispiro[acenaphthylene‐1,2′‐pyrrolidine‐3′,2″‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidine]‐2,3″‐diones in moderate yields. The structures of the products were determined and characterized thoroughly by NMR, MS, IR, elemental analysis, and X‐ray crystallographic analysis.     

One‐Pot ‘On‐solvent’ Multicomponent Protocol for the Synthesis of Medicinally Relevant 4H‐Pyrano[3,2‐c]quinoline Scaffold

‘One‐pot’ AcONa‐catalyzed transformation of salicylaldehydes, malononitrile and 4‐hydroxy‐1‐methylquinolin‐2(1H)‐one in the presence of a minimal quantity of EtOH results in fast (3 min) and efficient formation of unknown 2‐amino‐4‐(2‐hydroxyaryl)‐6‐methyl‐5‐oxo‐5,6‐dihydro‐4H‐pyrano[3,2‐c]quinoline‐3‐carbonitriles in 85–98% yields, which are potential pharmaceutical agents for treating disorders responsive to the induction of apoptosis, antiproliferation, or vascular disruption. This efficient ‘on‐solvent’ approach to the 4H‐pyrano[3,2‐c]quinoline scaffold represents a novel synthetic concept for multicomponent reaction (MCR) strategy and allows to combine the synthetic virtues of conventional MCR with ecological benefits and convenience of facile ‘on‐solvent’ procedure.     

DBU‐catalyzed Multicomponent Synthesis: Facile Access of 4,5,6,9‐Tetrahydro‐pyrido[3,2‐c]quinolines

An efficient synthesis of 4H,5H,6H,9H‐pyrido[ij]pyrano[3,2‐c]quinolines 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m , 4n , 4o , 4p , 4q , 4r , 4s , 4t as well as spiro compound 6 was achieved via multicomponent approach by using DBU as a nucleophilic catalyst under the remarkably mild reaction conditions. The structures of the compounds were characterized by ¹H NMR, ¹³C NMR, and mass spectral analysis. An attractive feature of this inexpensive protocol includes facile synthesis, shorter reaction time, ease of work‐up, large number of functional group tolerance, and good to excellent yields with high purity.