Synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones using nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl2 nanoparticles

Nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl₂ (nano‐[Zn‐2BSMP]Cl₂) as a nanoparticle Schiff base complex and a catalyst was introduced for the solvent‐free synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones by the multicomponent condensation reaction of various aromatic aldehydes, β‐naphthol, ethyl acetoacetate, and phenyl hydrazine at room temperature.     

Catalytic Applications of Nano‐Fe‐[Phenyl‐Salicylaldimine‐Methylpyranopyrazole]Cl2 as a Schiff Base Complex and Nanostructured Catalyst for the Synthesis of Hexahydroquinolines

By the four‐component condensation reaction of benzaldehyde with ethyl acetoacetate, malononitrile, and hydrazine hydrate using FeCl₂, a pyranopyrazole derivative was synthesized and then reacted with salicylaldehyde to give nano‐Fe‐[phenyl‐salicylaldimine‐methylpyranopyrazole]Cl₂ (nano‐[Fe‐PSMP]Cl₂). The prepared nano‐Schiff base complex was successfully used as an efficient catalyst for the synthesis of hexahydroquinolines.     

Synthesis of pyrano[2,3‐c]pyrazole derivatives using Fe3O4@SiO2@piperidinium benzene‐1,3‐disulfonate (Fe3O4@SiO2 nanoparticle‐supported IL) as a novel,green and heterogeneous catalyst

A simple, green and efficient protocol for the one‐pot four‐component synthesis of pyrano[2,3‐c ]pyrazole derivatives produced from reaction between aryl aldehydes, ethyl acetoacetate, malononitrile and hydrazine hydrate in the presence of nano magnetic piperidinium benzene‐1,3‐disulfonate was synthesized in water at 60 °C. The Fe₃O₄@SiO₂ nanoparticle‐supported IL was designed and synthesized. The present process offers advantages such as clean reaction, short reaction time, good to excellent yield, easy purification and easy recoverable catalyst.     

Action of Hydrazines on 2‐(2‐Oxindolin‐3‐ylidene)malononitrile, (E,Z)‐Ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate and Isatin‐β‐thiosemicarbazone as a Source of Spiro Indoline‐pyrazole Systems

2‐(2‐Oxindolin‐3‐ylidene)malononitrile ( 1a ) or (E,Z)‐ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate ( 1b ) or isatin‐β‐thiosemicarbazone ( 1c ) undergoes reactions with prototype hydrazine hydrate itself and some of its simple congeners to give hydrazone derivatives bearing indoline‐2‐one moiety ( 2 ). The hydrazone derivatives ( 2 ) when heated with acetyl acetone or ethyl acetoacetate in dry pyridine afforded the spiro indoline derivatives ( 3a , 3b ). Also, cinnoline derivative ( 9 ) is obtained by action of hydrazine hydrate on the N‐acetyl derivative of ( 6a ). The structures of the newly synthesized compounds were evaluated by IR, ¹H‐NMR spectroscopy, mass spectra and elemental analyses.     

微波辐射下吡啶[2,3-d]嘧啶衍生物的高效合成

本文以等摩尔的芳醛,巴比妥酸（或1,3-二甲基巴比妥酸）,5-氨基-2-甲基苯[d]噻唑为原料,以醋酸和乙二醇为溶剂,微波辐射下多组分一锅法合成了一系列新的吡啶[2,3-d]嘧啶衍生物。这种方法具有产率高,操作简便,反应时间短等优点。     

An Efficient and Green Synthesis of 6‐Amino‐3‐phenyl‐4‐aryl‐1,4‐dihydropyrano [2,3‐c]pyrazole‐5‐carbonitrile Derivatives under Ultrasound Irradiation in Aqueous Medium

A facile and eco‐friendly approach for the synthesis of 6‐amino‐3‐phenyl‐4‐aryl‐1,4‐dihydropyrano[2,3‐c]pyrazole‐5‐carbonitrile derivatives via four‐component reaction of hydrazine, ethyl 3‐oxo‐3‐phenylpropanoate, aldehydes, and malononitrile is described. The reaction is performed in water, without using any catalyst, and under ultrasound irradiation. The developed sonochemical‐assisted multi‐component reaction provides an improved and accelerated conversion when compared with conventional procedure.     

Glycerol: A Promising Benign Solvent for Catalyst‐free One‐pot Multi‐component Synthesis of 1H‐Pyrozolo[1,2‐b]phthalazine‐5,10‐diones and 2H‐Indazolo[2,1‐b]phthalazine‐triones Under Controlled Microwaves Irradiation

A simple green and efficient one‐pot multi‐component synthesis of 1H‐pyrozolo[1,2‐b]phthalazine‐5,10‐diones and 2H‐indazolo[2,1‐b]phthalazine‐triones has been developed utilizing one‐pot multi‐component reaction of aromatic aldehydes, active methylene reagents, phthalic anhydride, and hydrazine hydrate or alternatively phthalhydrazide in glycerol without catalyst under controlled microwave heating. The current synthetic protocol offers several advantages such as excellent yields, high EcoScale and atom economy, simple working up reactants and products, and the absence of hazardous catalysts or solvents.     

Synthesis of Pyrazolo‐[4́,3́:5,6]pyrido[2,3‐d]pyrimidine‐diones Catalyzed by a Nano‐sized Surface‐Grafted Neodymium Complex of the Tungstosilicate via Multicomponent Reaction

An inorganic–organic hybrid based on lanthanide clusters and Keggin type polyoxometalates (POMs) (Na[Nd (pydc‐OH)(H₂O)₄]₃}[SiW₁₂O₄₀]) was used the first time as trinuclear catalyst for one pot synthesis of pyrazolo[4??,3?:5,6]pyrido[2,3‐d]pyrimidine‐diones, via two different four and five‐component reactions involving hydrazine hydrate, ethyl acetoacetate, aryl aldehydes, and 6‐amino‐1,3‐dimethyl uracil or barbituric acid with ammonium acetate as alternative materials in green condition. To evaluate potential application of the as‐made hybrid in adsorption and separation processes, nitrogen adsorption was performed at 77 K through simulation study. The hybrid catalyst was further characterized via powder X‐ray diffraction (PXRD) at room temperature which indicated the good phase purity of the catalyst. The results show that the catalytic activity of the hybrid catalyst has increased relative to each parent component due to the special interaction between Keggin anions and pydc‐OH ligands.     

Synthesis of Highly Substituted Pyrrole and Dihydro‐1H‐Pyrrole Containing Barbituric Acids via Catalyst‐Free One‐Pot Four‐Component Reactions

A new one‐pot, four‐component reaction of phenylglyoxal or ethylglyoxalate, 1,3‐dicarbonyls, N ,N‐ dimethylbarbituric acid, and aromatic amines for the synthesis of highly substituted pyrroles or dihydro‐1H‐pyrrole containing barbituric acid in moderate‐to‐good yields is described. Short reaction time, mild reaction condition, use of simple experimental procedure, and prompt isolation of the products are some advantages of this protocol.     

An Efficient Synthesis of Chromeno[2,3‐d]pyrimidine‐2,4‐diones with a Nitroketene‐Aminal Moiety at C(5) by a One‐Pot Four‐Component Reaction

An efficient and novel synthesis of chromeno[2,3‐d]pyrimidine‐2,4‐dione derivatives with a nitroketene‐aminal moiety at C(5) via four‐component reaction of salicylaldehydes, barbituric acid, diamines, and 1,1‐bis(methylsulfanyl)‐2‐nitroethene in EtOH and in the presence of AcOH is reported. Easy performance, good yields, and easy purification are the main advantages of this method. All structures were confirmed by IR, MS, and ¹H‐ and ¹³C‐NMR, and by X‐ray crystal‐structure analyses. A plausible mechanism for this type of reaction is proposed (Scheme).     

Structural comparison of three N‐(4‐halogenophenyl)‐N′‐[1‐(2‐pyridyl)ethylidene]hydrazine hydrochlorides

2‐{1‐[(4‐Chloroanilino)methylidene]ethyl}pyridinium chloride methanol solvate, C₁₃H₁₃ClN₃⁺·Cl⁻·CH₃OH, (I), crystallizes as discrete cations and anions, with one molecule of methanol as solvent in the asymmetric unit. The N—C—C—N torsion angle in the cation indicates a cis conformation. The cations are located parallel to the (02) plane and are connected through hydrogen bonds by a methanol solvent molecule and a chloride anion, forming zigzag chains in the direction of the b axis. The crystal structure of 2‐{1‐[(4‐fluoroanilino)methylidene]ethyl}pyridinium chloride, C₁₃H₁₃FN₃⁺·Cl⁻, (II), contains just one anion and one cation in the asymmetric unit but no solvent. In contrast with (I), the N—C—C—N torsion angle in the cation corresponds with a trans conformation. The cations are located parallel to the (100) plane and are connected by hydrogen bonds to the chloride anions, forming zigzag chains in the direction of the b axis. In addition, the crystal packing is stabilized by weak π–π interactions between the pyridinium and benzene rings. The crystal of (II) is a nonmerohedral monoclinic twin which emulates an orthorhombic diffraction pattern. Twinning occurs via a twofold rotation about the c axis and the fractional contribution of the minor twin component refined to 0.324 (3). 2‐{1‐[(4‐Fluoroanilino)methylidene]ethyl}pyridinium chloride methanol disolvate, C₁₃H₁₃FN₃⁺·Cl⁻·2CH₃OH, (III), is a pseudopolymorph of (II). It crystallizes with two anions, two cations and four molecules of methanol in the asymmetric unit. Two symmetry‐equivalent cations are connected by hydrogen bonds to a chloride anion and a methanol solvent molecule, forming a centrosymmetric dimer. A further methanol molecule is hydrogen bonded to each chloride anion. These aggregates are connected by C—H...O contacts to form infinite chains. It is remarkable that the geometric structures of two compounds having two different formula units in their asymmetric units are essentially the same.     

An Efficient Four Component Domino Synthesis of Pyrazolopyranopyrimidines using Recyclable Choline Chloride:Urea Deep Eutectic Solvent

An efficient synthesis of pyrazolopyranopyrimidines was achieved by four component domino reaction of aldehydes, barbituric acid, hydrazine hydrate, and ethyl acetoacetate using biodegradable and recyclable choline chloride:urea as deep eutectic solvent. The reaction proceeds rapidly and affords the corresponding diverse tricyclic fused pyrazolopyranopyrimidines with a good to excellent yield. The protocol has the advantage of easy workup, high yields, and an environmentally benign methodology compared with other reported methods. The simplicity of this method makes it an interesting alternative to other approaches.     

Zwitterionic Salts from the Reaction of Symmetrical and Unsymmetrical (thio)Barbituric Acids with 2‐Pyridinecarbaldehyde under Solvent‐free Condition

A simple and efficient synthesis for the preparation of unusual charge‐separated pyridinium (thio)barbiturate zwitterion derivatives was achieved via a one‐pot reaction of (thio)barbituric acid derivatives and 2‐pyridinecarbaldehyde under solvent‐free condition and also in methanol under refluxing. The structure of the compounds was confirmed by ¹H NMR, ¹³C NMR, FT‐IR, mass and X‐ray analysis. The mechanism of the formation is discussed. Instead, no related pyridinium zwitterion was afforded from the reaction between dimedone and 2‐pyridinecarbaldehyde under the same conditions and its xanthene derivative was obtained.     

Nano–Mn‐[4‐nitrophenyl‐salicylaldimine‐methyl pyranopyrazole]Cl2 as a new nanostructured Schiff base complex and catalyst for the synthesis of hexahydroquinolines

By the reaction of 4‐nitrobenzaldehyde with ethyl acetoacetate, malononitrile and hydrazine hydrate, pyranopyrazole derivative as an active biological compound was synthsized and then reacted with salicylaldehyde and MnCl₂.4H₂O to afford nano‐Mn‐[4‐nitrophenyl‐salicylaldimine‐methyl pyranopyrazole]Cl₂ (nano‐[Mn‐4NSMP]Cl₂) for the first time. The produced Schiff base complex with nanostructured was fully characterized by Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), thermal gravimetric analysis (TGA), differential thermal gravimetric (DTG) and scanning electron microscope (SEM) and used it as an efficient catalyst for the preparation of hexahydroquinolines.     

A Catalyst‐free Green Protocol for the Synthesis of Pyranopyrazoles Using Room Temperature Ionic Liquid Choline Chloride‐urea

An efficient and rapid four component reaction of aldehydes, malanonitrile, β‐ketoesters and hydrazine hydrate (or phenyl hydrazine) in environmentally benign room temperature ionic liquid choline chloride‐urea has been developed for the synthesis of substituted 4H‐pyrano[2,3‐c]pyrazoles.     

A new nano‐Fe3O4‐supported organocatalyst based on 3,4‐dihydroxypyridine: an efficient heterogeneous nanocatalyst for one‐pot synthesis of pyrazolo[3,4‐b]pyridines and pyrano[2,3‐d]pyrimidines

A simple and practical strategy for the synthesis of a novel nano‐Fe₃O₄‐supported organocatalyst system based on 3,4‐dihydroxypyridine (Fe₃O₄/Py) has been developed. The prepared catalyst was characterized using Fourier transform infrared spectroscopy, transmission and scanning electron microscopies, X‐ray diffraction, vibrating sample magnetometry and energy‐dispersive X‐ray analysis. Accordingly, the Fe₃O₄/Py nanoparticles show a superparamagnetic property with a saturation magnetization of 61 emu g^?1, indicating potential application in magnetic separation technology. Our experimental results reveal that the pyridine‐functionalized Fe₃O₄ nanoparticles are an efficient base catalyst for the domino condensation of various aromatic aldehydes, Meldrum's acid and 5‐methylpyrazol‐3‐amine under very mild reaction condition and in the presence of ethanol solvent. Moreover, the synthesized catalyst was used for one‐pot, three‐component condensation of aromatic aldehydes with barbituric acid and malononitrile to produce 7‐amino‐2,4‐dioxo‐5‐phenyl‐2,3,4,5‐tetrahydro‐1H‐pyrano[2,3‐d]pyrimidine‐6‐carbonitriles. All reactions are completed in short times and all products are obtained in good to excellent yields. Also, notably, the catalyst was reused five times without significant degradation in catalytic activity and performance. Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis and reactions of 3‐amino‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]‐quinazolin‐9‐one and 2‐hydrazino‐3‐phenylamino‐3H‐quinazolin‐4‐one

The reaction of 3‐N‐(2‐mercapto‐4‐oxo‐4H‐quinazolin‐3‐yl)acetamide ( 1 ) with hydrazine hydrate yielded 3‐amino‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]quinazolin‐9‐one ( 2 ). The reaction of 2 with o‐chlorobenzaldehyde and 2‐hydroxy‐naphthaldehyde gave the corresponding 3‐arylidene amino derivatives 3 and 4 , respectively. Condensation of 2 with 1‐nitroso‐2‐naphthol afforded the corresponding 3‐(2‐hydroxy‐naphthalen‐1‐yl‐diazenyl)‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]quinazolin‐9‐one ( 5 ), which on subsequent reduction by SnCl₂ and HCl gave the hydrazino derivative 6. Reaction of 2 with phenyl isothiocyanate in refluxing ethanol yielded thiourea derivative 7. Ring closure of 7 subsequently cyclized on refluxing with phencyl bromide, oxalyl dichloride and chloroacetic acid afforded the corresponding thiazolidine derivatives 8, 9 and 10 , respectively. Reaction of 2‐mercapto‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 11 ) with hydrazine hydrate afforded 2‐hydrazino‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 12 ). The reactivity 12 towards carbon disulphide, acetyl acetone and ethyl acetoacetate gave 13, 14 and 15 , respectively. Condensation of 12 with isatin afforded 2‐[N‐(2‐oxo‐1,2‐dihydroindol‐3‐ylidene)hydrazino]‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 16 ). 2‐(4‐Oxo‐3‐phenylamino‐3,4‐dihydroquinazolin‐2‐ylamino)isoindole‐1,3‐dione ( 17 ) was synthesized by the reaction of 12 with phthalic anhydride. All isolated products were confirmed by their ir, ¹H nmr, ¹³C nmr and mass spectra.     

An efficient one pot synthesis of 3‐(2‐oxo‐2H‐chromen‐3‐yl)‐6H,8H‐pyrimido[4,5‐c]pyridazine‐5,7‐dionesl

An easy, simple and versatile one step synthesis of 3‐(2‐oxo‐2H‐chromen‐3‐yl)‐6H,8H‐pyrimido[4,5‐c]‐pyridazine‐5,7‐diones is reported by reaction of 3‐acetylcoumarins ( 1 ) with alloxan monohydrate ( 2 ) in acetic acid followed by hydrazine hydrate.     

Heterocyclic compounds from 4h‐3,1‐benzoxazin‐4‐one derivatives as anticancer agent

Behaviour of 2‐(4‐oxo‐4H‐benzo[d][l,3]oxazin‐2‐yl)‐benzoic acid (1) towards nitrogen nucleophiles namely, hydrazine hydrate, in different solvents, ammonium acetate, and o‐phenylenediamine has been investigated to give aminoquinazolin‐4‐one, benzotriazepinone, spiro‐type compound, and nitrogen bridgehead compounds 3‐5 , respectively. Also, reactivity of the aminoquinazolin‐4‐one 2 towards carbon elec‐trophiles such as ethyl acetoacetate, ethyl phenylacetate, ethyl chloroacetate, and aromatic aldehydes has been discussed. Reaction of Schiff s base 8 with sulfur nucleophiles namely o‐aminothiophenol and/or thio‐glycolic acid afforded Michael type adducts. Structural assignments, of products 1‐24 have been confirmed by elemental analysis and spectral data (¹H‐ and ¹³C ‐NMR and MS fragmentation). The bioassay indicates that some of the target compounds obtained have good selective anticancer activity.     

Unanticipated Heterocyclization from Reaction of Hydrazine Hydrate and/or Hydrazine Dihydrochloride with 1‐Ethyl‐4‐hydroxyquinolin‐2(1H)‐one

Unexpectedly, the reaction of 1‐ethyl‐4‐hydroxyquinolin‐2(1H)‐one ( 1 ) with hydrazine hydrate and/or hydrazine dihydrochloride led to three different products. In addition to the expected quninolinylhydrazine, two heteropentacycles, diquinopyrrole and diquinopyridazine, were afforded, depending on reaction conditions. The structure of the new products was established upon their spectral and analytical data.