An efficient and green synthesis of phthalide-fused pyrazole and pyrimidine derivatives

An efficient and green method for the synthesis of phthalide [isobenzofuran-1(3H)-one] fused pyrazoles via the catalyst-free condensation reaction of 2-formylbenzoic acid, hydrazine hydrate, and acetylenic esters in water is reported. Reaction of 2-formylbenzoic acid with 6-amino-uracils or cyclic 1,3-diketones resulted in the formation of phthalide-fused pyrimidine or cyclic 1,3-diketone derivatives.     

New "green" approaches to the synthesis of pyrazole derivatives

A novel approach to the synthesis of pyrazole derivatives from tosylhydrazones of alpha,beta-unsaturated carbonyl compounds possessing a beta-hydrogen is proposed, exploiting microwave (MW) activation coupled with solvent free reaction conditions. The cycloaddition was studied on three ketones (trans-4-phenyl-3-buten-2-one, beta-ionone and trans-chalcone). The corresponding 3,5-disubstituted-1H-pyrazoles were obtained in high yields and after short reaction times. In order to simplify and point out the green chemistry features of the method, a further improvement was achieved under the same catalytic conditions with a "one pot" synthesis of these heterocyclic compounds, starting directly from their carbonyl precursors via tosylhydrazones generated in situ. For an exhaustive study, the dielectric properties of the solid reaction mixtures were also measured, in order to obtain input data for the numerical simulation of their heating behaviour in the single mode MW cavity which was used for experimental work. In order to supply a valid methodology and tool for measuring the environmental impact, a comparative study between the synthetic route proposed and the classical synthetic route has been carried out.     

Efficient catalyst-free Domino approach for the synthesis of novel 2-benzazepine derivatives in water

A novel one-pot eco-friendly protocol for the synthesis of 2-benzazepine derivatives in water has been developed. 4-Chloro-3-formyl coumarin reacts with benzyl amines under catalyst-free conditions in aqueous medium to afford substituted 5-(2′-hydroxyaryl)-4-amido-2-benzazepines in excellent yields.     

Catalyst-free green synthesis and study of antioxidant activity of new pyrazole derivatives

In this research, a novel procedure for the synthesis of pyrazole derivatives in excellent yields was studied using catalyst-free multicomponent reaction of isoquinoline, activated acetylenic compounds, alkyl bromides, triphenylphosphine and hydrazine in water under ultrasonic irradiation at room temperature. The advantages of this procedure than to reported methods are short time of reaction, high yields of product, easy separation of product, clean mixture of reaction and green media for performing reaction. In addition, because of having pyrazole and isoquinoline core in the synthesized compounds, in this research, antioxidant activity of some synthesized compounds was investigated.     

A green,simple, catalyst-free,and efficient method for electro-organic synthesis of new benzofuran derivatives

In this work, the electrochemical oxidation of catechols 1a and 1b was studied in the presence of pyrazolidine-3,5-dione (3a), as a nucleophile, in a mixture of ethanol and a phosphate buffer solution (0.1 M, pH 7), as a green medium, using the cyclic voltammetry and controlled-potential coulometry techniques. The results obtained indicated that the oxidized forms of these catechols (2a and 2b) participated in the Michael addition reactions with pyrazolidine-3,5-dione (3a), and converted, via an ECEC mechanism, to their corresponding benzofurans (7a and 7b). In this work, some new benzofuran derivatives were synthesized with good yields and high purities using a facile, one-pot, and environmentally friendly electrochemical method in the absence of any chemical catalyst, toxic solvent, and hard conditions.     

New synthesis of pyrazole and isoxazole derivatives

A convenient synthesis of 5-aryl-1-phenylpyrazoles and 5-arylisoxazoles, from readily available ketimine 1 dimethylformamide dimethylacetal and phenylhydrazine or hydroxylamine, is described.     

A mild and green chemistry approach for the synthesis of symmetrical spirooxindole derivatives

A simple and eco-friendly synthesis of the biologically important spirooxindole scaffold was done by the reaction of isatin with activated pyrazolones in the presence of a catalytic amount of p-toluenesulfonic acid in water at room temperature. A variety of symmetrical spirooxindole derivatives were obtained with excellent yields within short reaction time. This method is of great value because of its environmentally benign character, high yield, and easy handling.     

Green and catalyst-free synthesis of aminoanthraquinone derivatives in solvent-free conditions

In this study, new derivatives of aminoanthraquinone have been synthesized via one-pot three-component condensation reaction of 1- and 2-amino anthraquinones, triethyl orthoformate and CH-acid compounds without using any solvent or catalyst in mild temperature (50 °C). This simple and efficient method yields the desired products in short reaction time (14–50 min) and good to excellent yields (85–96%). Moreover, chemical structures of synthesized products have been entirely confirmed by FT-IR, ¹H and ¹³CNMR and mass spectroscopy and melting points.

     

Novel pyrazoline and pyrazole porphyrin derivatives: synthesis and photophysical properties

2-Vinyl-5,10,15,20-tetraphenylporphyrinatozinc(II) reacts with nitrile imines, generated in situ from ethyl hydrazono-α-bromoglyoxylates, affording the corresponding pyrazolines in good to excellent yields. Treatment of pyrazoline derivatives with DDQ affords the corresponding pyrazole derivatives with moderate to excellent yields. When the hydrolysis of ester group in the pyrazoline derivatives was considered, it was observed the concomitant oxidation of the heterocyclic unit, which allowed directly obtaining porphyrin-pyrazole derivatives with a carboxylic group, in very good yields.The photophysical properties of the pyrazoline and pyrazole porphyrin derivatives show that the influence of the heterocyclic substituents is limited by the tendency of these molecules to aggregate. All other properties and especially the triplet kinetics remain unaffected. The adducts with low tendency to aggregate showed very high singlet oxygen yield, which makes these compounds interesting for their use as photosensitizers for PDT.     

A green protocol for catalyst-free synthesis of 1-oxo-hexahydroxanthenes in aqueous medium

An efficient and eco-friendly synthesis of 1-oxo-hexahydroxanthenes has been expediently accomplished by a reaction of salicylaldehyde with cyclohexane-1,3-dione or dimedone in water as universal solvent at reflux condition without a catalyst. Excellent yields of the products, operational simplicity, simple work-up and catalyst-free synthesis are attractive features of this green protocol.     

Water-mediated,green, and efficient synthesis of bisquinolones under catalyst-free conditions

Water-mediated, green, and efficient synthesis involving condensation of 4-hydroxy-1-methylquinoline-2(1H)-one (3) with different aromatic and heterocyclic aldehydes (4a–n) leading to 3,3′-(arylmethylene)-bis-(4-hydroxy-1-methylquinolin-2(1H)-one) 5(a–n) under catalyst-free conditions is described. This reaction has an easy workup without using column chromatography and provides excellent yields of the products in shorter reaction times. It does not require any catalyst and uses water as the medium which is the greenest solvent. 3 required in this work was itself obtained by condensation of N-methylaniline (1) with malonic acid (2) in the presence of POCl₃ using a previously reported procedure.     

New synthesis of 3-methoxy-4-substituted pyrazole derivatives

A simple and efficient protocol for the synthesis of 3-methoxy-4-arylmethylene- and 3-methoxy-4-heteroarylmethylenepyrazoles has been developed. These derivatives are obtained in one step from alcohols 3 or 8a-b.     

Citric acid:An efficient and green catalyst for rapid one pot synthesis of quinoxaline derivatives at room temperature

The condensation of o-phenylenediamines with 1,2-dicarbonyl compounds in the presence of citric acid afforded the corresponding quinoxaline derivatives in higher yields at room temperature in ethanol,and most of the reactions were completed in less than 1 min.     

Sulfamic acid as a green,reusable catalyst for stepwise,tandem & one-pot solvent-free synthesis of pyrazole derivatives

Sulfamic acid (SA) is a bi-functional, cost-effective and reusable green catalyst for the synthesis of 4- (pyrazol-4-yl)methylenepyrazol-5(4H)-one derivatives by one-pot, three-component condensation of pyrazol-4-carbaxaldehydes, β-ketoesters and phenyl hydrazine (Route-I). In addition to this method, another simple condensation of pyrazol-4-carbaxaldehydes with pyrazolone in the presence of SA under the solvent-free condition in good yield is reported. The merits of these protocols are mild conditions, non-aqueous workup, high yields, easy availability of the catalyst, no chromatographic separation and inexpensive solid acid catalyst. Furthermore, SA could be recycled and reused for five times without losing its catalytic activity.     

An ultrasound-promoted green approach for the N-formylation of amines under solvent- and catalyst-free conditions at room temperature

A new environmentally benign, convenient, and facile methodology for the N-formylation of amines is reported using ultrasound irradiation under solvent- and catalyst-free conditions at room temperature. Compared with conventional methods, the main advantages of the present procedure are milder, cleaner and greener conditions, shorter reaction time, higher purity and yields, simpler work-up, and lower generation of waste or pollutions.     

A green approach for synthesis of naphthoquinone-fused oxazine derivatives in water under ultrasonic irradiation

An efficient and eco-friendly procedure has been developed for synthesis of naphthoquinone-fused oxazine derivatives via one-pot pseudo four-component reaction of 2-hydroxy-1,4-naphthoquinone, aromatic amine and formaldehyde in water under ultrasound irradiation. This protocol has the advantages of being catalyst-free, with short reaction times and high yields, and being environmentally benign with an easy work-up.     

Studies on 5-aminopyrazole derivatives synthesis of some new fused pyrazole derivatives

5-Amino-4-cyano-3-phenylpyrazole (1) reacts with acrylonitrile or ethyl acrylate to yield 4-cyano-3-phenyl-4,5,6,7-tetrahydro-5-oxopyrazolo-[1,5-a]-pyrimidine (2). With urea, thiourea and ethyl acetoacetate1 gives the pyrazolopyrimidine derivatives6a,6b, and7 respectively. On the other hand, compound1 reacted with benzoylisothiocyanate to give the corresponding thiourea derivative4. Diazotized1 was coupled with malononitrile and ethyl cyanoacetate to yield the pyrazolopyrimidine derivatives10 and11, respectively, whereas on coupling with -chloro acetoacetic ester and with acetylacetone the hydrazones12 and13 were obtained.

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Untersuchungen an 5-Aminopyrazolderivaten. Synthese von verschiedenen neuen kondensierten Pyrazolderivaten

Zusammenfassung Die Reaktion von 5-Amino-4-cyano-3-phenylpyrazol (1) mit Acrylnitril oder Ethylacrylate ergibt 4-Cyano-3-phenyl-4,5,6,7-tetrahydro-5-oxopyrazolo-[1,5-a]-pyrimidin (2). Die Reaktion von1 mit Harnstoff, Thioharnstoff und7. Ethyl acetoacetat ergibt die Pyrazolopyrimidinderivate6a,6b und7. Andererseits entsteht das Thioharnstoffderivat4 durch die Reaktion von1 mit Benzoylisothiocyanat. Diazotiertes1 koppelt mit Malononitril und Ethylcyanoacetat zu den Pyrazolopyrimidinen10 und11, die Kopplung mit -chloroacetoacetic ester und Acetylaceton ergibt jedoch die Hydrazone12 und13.

     

Uses of cyanoacetylhydrazine in heterocyclic synthesis: novel synthesis of pyrazole derivatives with anti-tumor activities

The reaction of cyanoacetylhydrazine with chloroacetyl chloride gave N'-(2-chloroacetyl)-2-cyanoacetohydrazide. The latter underwent cyclization to afford 1-(5 amino-3-hydroxy-1H-pyrazol-1-yl)-2-chloroethanone, which underwent nucleophilic substitution to give 3-(5-amino-3-hydroxy-1H-pyrazol-1-yl)-3-oxopropanenitrile. The latter two compounds were used as key synthons to synthesize new thiophene, pyran, thiazole and some fused heterocyclic derivatives. The antitumor activity of the newly synthesized compounds was evaluated against three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) and some of these compounds were found to exhibit much higher inhibitory effects towards the three tumor cell lines than the Gram positive control doxorubicin.     

Microwave-assisted synthesis,characterization and biological activity of novel pyrazole derivatives

A series of 1-(4-substitutedphenyl)-3-phenyl-1H-pyrazole-4-carbaldehydes 4a–l have been synthesized and tested for their biological activities. Formation of the pyrazole derivatives was achieved by treating with Vilsmeier-Haack reagent. The newly synthesized compounds were evaluated for their anti-inflammatory and analgesic activities compared to Diclofenac sodium as standard drug. Compounds 4g, 4i and 4k exhibited the maximum anti-inflammatory and analgesic activities. The detailed synthesis, spectroscopic and toxicity data are reported.