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.     

Organocatalyzed Enantioselective Synthesis of 2‐Amino‐4H‐chromene Derivatives

Optically active 2‐amino‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene‐3‐carboxylates, 2‐amino‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene‐3‐carbonitriles, and 2‐amino‐8‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene‐3‐carbonitriles were synthesized. Using cinchona alkaloid‐derived bifunctional catalysts, the corresponding 2‐amino‐4H‐chromene derivatives were obtained in high yields and moderate to high ee values (up to 82% ee) from the tandem Michael addition–cyclization reaction between 1,3‐cyclohexanediones or 1,2‐cyclohexanediones and (E )‐3‐aryl‐2‐cyanoacrylate or alkylidene malononitrile derivatives.     

One‐Pot Synthesis of Functionalized 2H‐Chromene (=2H‐1‐Benzopyran) Derivatives via a Three‐Component Reaction between a CH‐Acid,a Dialkyl Acetylenedicarboxylate,and Methyl Chloroglyoxylate or Benzyl Carbonochloridate Mediated by Triphenylphosphine

An effective route to functionalized 2H‐chromene (=2H‐1‐benzopyran) derivatives 4 is described (Scheme 1). This involves the reaction of a 1,1‐diactivated alkene, resulting from the reaction of dimedone (=5,5‐dimethylcyclohexane‐1,3‐dione; 1a ) with methyl chloroglyoxylate (ClC(O)COOMe), benzyl carbonochloridate (ClC(O)OCH₂Ph) or 3,5‐dinitrobenzoyl chloride (3,5‐(NO₂)₂C₆H₃C(O)Cl), and a dialkyl acetylenedicarboxylate (=dialkyl but‐2‐ynedioate) in the presence of Ph₃P which undergo intramolecular Wittig reaction to produce 2H‐chromene derivatives (Scheme 1).     

3‐(3,5‐Dimethyl‐1H‐Pyrazol‐1‐yl)‐3‐Oxopropanenitrile as Precursor for Some New Mono‐Heterocyclic and Bis‐Heterocyclic Compounds

3‐(3,5‐Dimethyl‐1 H ‐pyrazol‐1‐yl)‐3‐oxopropanenitrile 1 was used as a cyanoacetylating agent for synthesis of the acetanilide derivative 3 . Compound 3 was utilized as a key intermediate for the synthesis of some new mono‐chromene and di‐chromene derivatives 9 and 13 , the dihydrazo derivatives 15 , and the dithiazole derivatives 18 via the condensation with o‐hydroxybenzaldehyde derivatives, the coupling with aryl diazonium salts, or the reaction with phenyl isothiocyanate in presence of KOH followed by phenacyl bromide derivatives respectively.     

An Approach to the Synthesis of 7‐Amino‐6‐imino‐9‐phenyl‐6H‐benzo[c]chromene‐8‐carbonitrile Derivatives via a Three‐Component Reaction under Ultrasonic Irradiation

An efficient synthesis of 7‐amino‐6‐imino‐9‐phenyl‐6H‐benzo[c]chromene‐8‐carbonitrile derivatives 3 by a three‐component reaction of salicylaldehydes (=2‐hydroxybenzaldehydes) 1 , malononitrile (=propanedinitrile), and 2‐(1‐arylethylidene)malononitrile 2 under ultrasonic irradiation in EtOH is reported. Good yields, short reaction times, and easy purification are the main advantages of the present method. The structures were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).     

An Efficient and Chemoselective Knoevenagel/Hemiketalization Process for the Synthesis of New 2H‐Chromenes in a One‐Pot Three‐Component Reaction

A novel L ‐proline‐catalyzed mild and ecological approach towards the synthesis of 2H‐chromene derivatives was achieved by Knoevenagel reaction followed by an intramolecular hemiketalization process. In the present protocol, chemoselectivity has been successfully achieved by using L ‐proline as catalyst. This eco‐friendly and chemoselective reaction provided an alternative synthetic method to prepare previously unknown 2H‐chromene derivatives in a one‐pot reaction.     

Zinc chloride‐catalyzed one‐pot,three‐component synthesis of 5,8‐dihydro‐5,8‐dioxo‐4H‐chromene derivatives

An efficient zinc chloride‐catalyzed one‐pot synthesis of 5,8‐dihydro‐5,8‐dioxo‐4H‐chromene derivatives have been achieved by the reaction of 2,5‐dihydroxy‐6‐undecyl‐1,4‐bezoquinone, cyanothioacetamide, and aromaticaldehyde, in EtOH at room temperature. The structures of the products were characterized by IR, ¹H‐NMR, mass spectra, and elemental analyses. J. Heterocyclic Chem., (2011).     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

Novel regioselective synthesis of 3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐one containing compounds

A variety of 3″,5″‐diaryl‐3″H,4′H‐dispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]thiadiazol]‐4′‐ones 3a‐c were synthesized regioselectively through the reaction of 4′H,5H‐trispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]oxadithiino[5,6‐c]chromene‐5″,1″′‐cyclohexan]‐4′‐one ( 1 ) with nitrilimines (generated in situ via triethylamine dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a‐c ) in refluxing dry toluene. Single crystal X‐ray diffraction studies of 3a,b add support for the established structure. Similarly, 3′,5′‐diaryl‐2,2‐dimethyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5a‐c were obtained in a regioselective manner through the reaction of 2,2,5′,5′‐tetramethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino[5,6‐c]chromen]‐4‐one ( 4a ) with nitrilimines under similar reaction conditions. On the other hand, reaction of 2,5′‐diethyl‐2,5′‐dimethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino‐[5,6‐c]chromen]‐4‐one ( 4b ) with nitrilimines in refluxing dry toluene afforded the corresponding 3′,5′‐diaryl‐2‐ethyl‐2‐methyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5d‐f as two unisolable diastereoisomeric forms.     

Synthesis and Pharmacological Evaluation of Some New Chromeno[3,4‐c]pyrrole‐3,4‐dione‐based N‐Heterocycles as Antimicrobial Agents

The reaction of 2‐oxo‐2H‐chromene‐3‐carboxamide ( 1 ) with carbon disulfide afforded 1‐mercaptopyrrolo[3,4‐c ]chromene‐3,4‐dione ( 3 ). The latter compound was utilized as versatile building block for new azole systems via incorporating in a series of manipulations including cyclocondensation reactions. The structure of the newly synthesized compounds has been confirmed by IR, ¹H NMR, ¹³C NMR, mass spectral, and elemental analysis. Furthermore, some selected compounds were screened in vitro for their antimicrobial activities. The results declared that most of the synthesized compounds have high antimicrobial activity.     

An Efficient Synthesis of Mono and Bis‐1,2,3‐triazole AZT Derivatives via Copper(I)‐catalyzed Cycloaddition

An efficient synthesis of novel mono and bis‐1,2,3‐triazoles 3′‐azido‐2′‐deoxythymidine (AZT) derivatives via copper(I)‐catalyzed 1,3‐dipolar cycloaddition reaction is described. Starting from AZT and terminal alkyne derivatives, mono and bis‐1,2,3‐triazole AZT derivatives are regioselectively obtained in good yields under mild conditions using CuSO4·5H2O and sodium ascorbate as a catalyst system, and t‐BuOH/H₂O (1:1, v/v) as a co‐solvent. The structures of these compounds were elucidated by IR, HR MS and NMR.     

Synthesis,Characterization, and In Vitro Microbial Evaluation of Some New 4H‐Chromene and Quinoline Derivatives of 1H‐Pyrazole

A new series of nine derivatives of 4H‐pyrano[3,2‐c]chromene and 12 derivatives of N‐thiazolyl‐4H‐quinoline of 1H‐pyrazole has been synthesized by one pot base catalyzed cyclocondensation reaction of 1H‐pyrazole‐4‐carbaldehyde, malononitrile, and 4‐hydroxy coumarin or β‐enaminones, respectively. All the synthesized compounds were characterized by elemental analysis, FT‐IR, ¹H NMR, ¹³C NMR spectral data and were further screened, against a panel of pathogenic strains of bacteria and fungi.     

Triethanolamine‐catalyzed expeditious and greener synthesis of 2‐amino‐4H‐chromenes

Triethanolamine (TEOA), an inexpensive and eco‐friendly base, was used to efficiently catalyze the three‐component condensation reaction of heterocyclic/aromatic aldehyde, (α/β)‐naphthol, and malononitrile in water to give the corresponding substituted 2‐amino‐4H‐chromene derivatives with excellent yields.     

Rhodium(III)‐Catalyzed Transannulation of Cyclopropenes with N‐Phenoxyacetamides through CH Activation

An efficient rhodium(III)‐catalyzed synthesis of 2H‐chromene from N‐phenoxyacetamides and cyclopropenes has been developed. The reaction represents the first example of using cyclopropenes as a three‐carbon unit in rhodium(III)‐catalyzed C(sp²)? H activations.     

An Efficient Five‐Component Reaction for the Synthesis of 4,4′‐((2‐Oxoindoline‐3,3‐diyl)bis(methylene))bis(2‐aryl‐1H‐pyrrolo[3,4‐c]quinoline‐1,3(2H)‐dione) Derivatives

An efficient cascade process five‐component reaction of isatins and 3‐oxo‐N‐arylbutanamide for the synthesis of 4,4′‐((2‐oxoindoline‐3,3‐diyl)bis(methylene))bis(2‐aryl‐1H‐pyrrolo[3,4‐c]quinoline‐1,3(2H)‐dione) derivatives was reported under mild condition. The advantages of this strategy are easy to obtain raw materials, convenient one‐pot procedure, and simple operation.     

Structural,spectroscopic and first‐principles studies of new aminocoumarin derivatives

The new aminocoumarin derivatives 3‐[1‐(3‐hydroxyanilino)ethylidene]‐3H‐chromene‐2,4‐dione, ( 1 ), 3‐[1‐(4‐hydroxyanilino)ethylidene]‐3H‐chromene‐2,4‐dione, ( 2 ), and 3‐[1‐(2‐hydroxyanilino)ethylidene]‐3H‐chromene‐2,4‐dione, ( 3 ), all C₁₇H₁₃NO₄, were synthesized by reacting an equimolar amount of 3‐acetyl‐4‐hydroxycoumarin and the corresponding aminophenol in absolute ethanol. Structural and spectroscopic analysis of these phases revealed that derivatives ( 1 ) and ( 2 ) are isomers of previously reported ( 3 ) [Brahmia et al. (2013). Acta Cryst. E 69 , o1296]. The crystal structures of meta derivative ( 1 ) and para derivative ( 2 ) were ab initio determined from powder X‐ray diffraction data using the direct‐space approach. Both ( 1 ) and ( 2 ) adopt the orthorhombic space group P2₁2₁2₁. These isomers show hydrogen bonds and rich π–π stacking, together with π…H interactions, which are built by conjugated systems of coumarin and phenol rings. In the crystalline lattice, the packing of ( 1 ) and ( 3 ) are mainly stabilized through O—H…O hydrogen bonding between neighbouring coumarin molecules, while hydrogen bonds between coumarin and water molecules build the stable crystal structure of derivative ( 2 ). A big similarity in the skeletons of the IR spectra of these isomers was noticed. Derivative ( 2 ) exhibits two weak bands which were not present in the spectra of the other two derivatives, at 2370 and 2948 cm^?1, which can be assigned to the O—H vibrations of the solvent (H₂O) trapped in the structure of ( 2 ). These aminocoumarin derivatives display absorption maxima in the visible region, attributed to π–π delocalization involving the whole electronic system of the compounds with a considerable charge‐transfer character originating from the aminophenyl ring and pointing towards the coumarin system which is characterized by a high electron‐accepting character. Additionally, the isolated molecular ground‐state geometries were optimized at the PBE0/TZP level and the electronic properties, molecular electrostatic potential and Hirshfeld charges were determined.     

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.     

Reaction of 2‐Imino‐2H‐chromene‐3‐carboxamide with Phosphorus Isothiocyanates: First Synthesis of Novel Chromeno[2,3‐d]pyrimidinyl and Bis(chromeno[2,3‐d]pyrimidinyl)phosphines and Chromeno[2′,3′:4,5]pyrimido[2,1‐d][1,3,5,2]triazaphosphinine

Novel chromeno[2,3‐d]pyrimidinyl and bis(chromeno[2,3‐d]pyrimidinyl)phosphines and chromeno[2′,3′:4,5]pyrimido[2,1‐d][1,3,5,2]triazaphosphinine were obtained in a simple one‐pot procedure via treatment of 2‐imino‐2H‐chromene‐3‐carboxamide with phenyl phosphorus isothiocyanates. Possible reaction mechanisms were proposed. The structures of the obtained products were confirmed by elemental analyses and spectral tools.     

Chemical Reactivity of 4,9‐Dimethoxy‐5‐oxo‐5H‐furo[3,2‐g]chromene‐6‐Carboxaldehyde Toward Some Nucleophilic Reagents

The chemical reactivity of 4,9‐dimethoxy‐5‐oxo‐5H‐furo[3,2‐g ]chromene‐6‐carboxaldehyde (6‐formylkhellin) ( 1 ) was studied toward a diversity of nitrogen nucleophilic reagents. Reaction of carboxaldehyde 1 with some primary amines and heterocyclic amines afforded the corresponding Schiff bases. Also, the reactivity of carboxaldehyde 1 was studied toward some hydrazine derivatives, namely 7‐chloro‐4‐hydrazinoquinoline, 3‐hydrazino‐5,6‐diphenyl‐1,2,4‐triazine, N⁴‐phenylthiosemicarbazide, and S‐benzyldithiocarbazate. 6‐Formylkhellin ( 1 ) underwent ring transformation upon treatment with hydroxylamine hydrochloride producing 5‐hydroxy‐4,9‐dimethoxy‐7‐oxo‐7H‐furo[3,2‐g ]chromene‐6‐carbonitrile ( 22 ). Some pyrimidine, [1,2,4]triazolo[4,3‐a ]pyrimidine, tetrazolo[1,5‐a ]pyrimidine, and diazepine derivatives linked benzofuran were efficiently synthesized. Reaction of carboxaldehyde 1 with a variety of 1,4‐binucleophiles produced furochromone‐fused benzodiazepine, pyridotriazepine, benzoxazepine, and benzothiazepine derivatives. Some unsymmetrical thiocarbohydrazones were also synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Facile One‐pot,Three‐component Synthesis of Novel Bis‐heterocycles Incorporating 5H‐chromeno[2,3‐b]pyridine‐3‐carbonitrile Derivatives

Novel bis‐chromeno[2,3‐b ]pyridine derivatives were synthesized with good yields by a clean and efficient methodologies involving one‐pot three‐component synthesis of bis‐aldehydes, malononitrile dimer, and dimedone in the presence of piperidine as a catalyst in EtOH. Depending on the length and position of the spacer in the bis‐aldehyde derivatives 1 , the reactions proceeded to give either the bis(2,4‐diamino‐tetrahydro‐5H‐chromeno[2,3‐b ]pyridine‐3‐carbonitriles) 4 or bis(4‐amino‐2,6‐dioxo‐hexahydro‐2H‐chromeno[2,3‐b ]pyridine‐3‐carbonitriles) 5 . All of the new compounds have been characterized by spectral data.