N-Arylation of nitrogen heterocycles with 2,4-difluoroiodobenzene

Arylation reactions of NH-heterocycles [specifically, pyrazole, 3-(trifluoromethyl)pyrazole, imidazole and pyrrole] with 2,4-difluoroiodobenzene in the absence and presence of copper catalysis are described. The combination of fluoro and iodo substituents in the same aryl substrate has facilitated both S_NAr reactions at the C-F bonds and copper-catalysed Ullmann-type coupling reactions at the C-I bond. Products arising from regioselective reactions and multiple substitutions have been isolated, providing a range of new N-arylated pyrazole, imidazole and pyrrole derivatives.     

Study of some reactions of ethyl 4-phenyl-3-benzoyl-2-pyrazoline-5-carboxylate

Several reactions of the pyrazoline 1a were investigated. With bromine water, potassium permanganate, hydrogen peroxide, or potassium hydroxide, different pyrazole derivatives were formed. While the reaction with hydroxylamine or some hydrazines gave the corresponding pyrazoline Schiff bases, with aroylhydrazines, pyrazole Schiff bases were formed.     

A new synthesis of substituted pyrazoles from 1,4-dianions of phenylhydrazones having an α-hydrogen

The 1,4-dianions of acetophenone, para-substituted acetophenones, deoxybenzoin and dibenzyl ketone phenylhydrazone were prepared by treatment of the respective phenylhydrazone with two molecular equivalents of n-butyllithium in tetrahydrofuran-hexane at 0° and condensed with a variety of aromatic esters, followed by acid cyclization to give the substituted pyrazole in good yield. The synthesis procedure appears to be a convenient and unequivocal method for preparing a particular pyrazole isomer without interfering side reactions. The 1,4-dianion of N,N-diphenylsemicarbazone was also prepared, and the condensation-cyclization gave the pyrazole in somewhat lower yield.     

Specificity of the reaction of β-carboxyvinyl(triphenyl)phosphonium chloride with azoles

Reactions of pyrazole, 3,5-dimethylpyrazole, 1,2,4-triazole, 5-aminotetrazole, and imidazole with β-carboxyvinyl(triphenyl)phosphonium chloride in boiling acetonitrile are accompanied by elimination of azole with formation of the initial salt and elimination of triphenylphosphine to give the corresponding azole hydrochloride and α-azolyacrylic acid. In all cases, ethylenebis(triphenylphosphonium) dichloride was formed, and the reactions with the most nucleophilic 3,5-dimethylpyrazole and imidazole also led to their adducts with α-azolylacrylic acid. In the reactions of pyrazole and 3,5-dimethylpyrazole with β-carboxyvinyl-(triphenyl)phosphonium chloride at room temperature, the conesponding addition products were isolated in almost quantitative yield.     

Microwave-assisted solvent-free N-arylation of imidazole and pyrazole

Solvent-free coupling reactions between imidazole or pyrazole and aryl bromides were achieved with microwave irradiation using copper salts and l-amino acids as catalysts.     

Synthesis of Polysubstituted Pyrazolo[3,4‐b]pyridine‐3‐Carbohydrazide and Pyrazolo[3,4‐d]pyridazine Derivatives

5‐Amino‐4‐formyl pyrazole carboxylate gave facile reactions with malononitrile, hydrazine, and ketones in the presence of piperidine furnished substituted pyrazolo[3,4‐b]pyridines and pyrazolo[3,4‐b]quinolones. The pyridazine sulfonamides were obtained by the reaction of 5‐chloro 4‐formyl pyrazole carboxylate with sulfonamide derivatives.     

An efficient synthesis of pyrazole chalcones under solvent free conditions at room temperature

An easy,safe,solvent free and effective method for the synthesis of pyrazole-substituted chalcones has been achieved by grinding pyrazole aldehydes and acetophenones in the presence of activated barium hydroxide(C-200) in high yield within short span of time.All reactions were carried out just by grinding the two reactants in the presence of activated barium hydroxide(C-200). Results are also compared with sodium hydroxide and potassium hydroxide.     

Pyrazoles. XVIII. Synthesis of a novel tripyrazolyl by two consecutive cine substitution reactions

Preparation of the C-N coupled tripyrazolyl VII, by two consecutive cine substitution reactions starting from 1,4-dinitropyrazole and using pyrazole as a nucleophile, is described. Solvent dependent nitrations of 4-nitro-3(5)-(1′-pyrazolyl)pyrazole I are reported.     

Deprotonation of pyrazole and its analogs by aqueous copper acetate in the presence of triethylamine

Deprotonation reactions of pyrazole and its analogs by aqueous copper acetate in benzene at room temperature in the presence of triethylamine were studied. Unlike 3,5-dimethylpyrazole, more acidic pyrazole, 5-methyl-3-trifluoromethylpyrazole, and 3,5-bis(trifluoromethyl)pyrazoles are deprotonated to give pyrazolate bridges. The structural features of the obtained compounds are discussed based on X-ray diffraction data.     

Microwave versus ultrasound assisted synthesis of some new heterocycles based on pyrazolone moiety

Different pyrazolone derivatives were prepared by microwave irradiation and ultrasound assisted methods besides the traditional ones. They were used for synthesis of some derivatives of spiropiperidine-4,4′-pyrano[2,3-c]pyrazole, dihydropyrano[2,3-c]pyrazole, pyrazole-4-carbothioamide, 4-(2-oxo-1,2-diphenylethylidene)-1H-pyrazol-5(4H)-one, azopyrazole, arylmethylenebis-1H-pyrazol-5-ol and araylidene-1H-pyrazol-5(4H)-one via reactions with different reagents applying the ultrasound method in some cases.     

Syntheses of 1-substituted-3-aminopyrazoles

A series of 1-substituted-3-aminopyrazoles were prepared via Chan-Lam coupling reactions, alkylation, and pyrazole ring formation.     

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

Pyrazole and its derivatives are considered a privileged N-heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.     

Studies on the reactions of cyclic oxalyl compounds with hydrazines or hydrazones : Synthesis and reactions of 4‐benzoyl‐1‐(3‐nitrophenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxylic acid

The 1H‐pyrazole‐3‐carboxylic acid 2 , obtained from the furan‐2,3‐dione 1 and N‐Benzylidene‐N'‐(3‐nitrophenyl) hydrazine, was converted via reactions of its acid chloride 3 with various alcohols or N‐nucleo‐philes into the corresponding ester or amide derivatives 4 or 5 , respectively. Nitrile 6 and anilino‐pyrazole acid 7 derivatives of 2 were also obtained by dehydration of 5a in a mixture of SOCl₂ with DMF and reduction of 2 with sodium polysulphide, respectively. While cyclocondensation reactions of 2 or 7 with phenyl hydrazine or hydrazine hydrate and 6 with only anhydrous hydrazine lead to derivatives of pyrazolo[3,4‐d]‐pyridazinone 8 and pyrazolo[3,4‐d]pyridazine amine 9 , respectivel. The reaction of 2 with 2‐hydrazinopyri‐dine provided hydrazono‐pyrazole acid derivative 10 , which was decarboxylated to give hydrazono‐pyra‐zole derivative 11 . Pyrazolo[4,3‐d]oxazinone 12 and 2‐quinolyl pyrazolo[3,4‐d]pyridazine 13 derivatives were also prepared by cyclocondensation reactions of 2 with hydroxylamine hydrochloride and 7 with acetaldehyde, respectively.     

Synthesis of polycyclic pyrazoles through formation of the first fused heterocyclic o-quinodimethane intermediate

1-Benzoyl-4,6-dibromo-3-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole (2) was used as a precursor for o-quinodimethane 3, which was trapped by in situ reactions with dienophiles to give bridged pyrazole derivatives.     

Synthesis of pyrazolo[1,5-a]indoles via copper(I)-catalyzed intramolecular amination

A variety of pyrazolo[1,5-a]indole derivatives were synthesized via Cu(I)-catalyzed intramolecular amination reactions. This novel method provides a general and efficient synthesis to indoles fused with pyrazole rings in high yields.     

The synthesis of electron donor-acceptor substituted pyrazoles

A variety of 1,3- and 1,5-donor-acceptor substituted pyrazole derivatives have been synthesized by the cyclocondensation of α,β-ethynyl ketones with substituted phenyl hydrazines. The regioselectivity of the cyclization depends on the reaction conditions in a manner consistent with competitive 1,2- and 1,4-addition followed by ring closure. 1,4-Disubstituted derivatives can be prepared from the corresponding 4-iodopyrazole using palladium catalyzed carbon-carbon bond forming reactions. The pyrazole chromophores are expected to show interesting nonlinear optical properties.     

Green Synthesis of Pyrazole and Oxazole Derivatives

New intermediate 3‐methyl‐5‐oxopyrazol propanenitrile was synthesized by one pot three component reactions using ethyl cyanoacetate, hydrazine hydrate, and ethyl acetoacetate and was used for the synthesis of new oxazole and pyrazole derivatives. All reactions were carried out using eco‐friendly solvents and without catalyst.     

Synthesis and Properties of 2,2-Dichlorovinyl Trifluoromethyl Ketone

Highly reactive 2,2-dichlorovinyl trifluoromethyl ketone was synthesized. Its reactions with N,N-and N,S-nucleophiles gave 1,3-thiazine, pyrazole, and imidazole derivatives containing a trifluoromethyl substituent.     

5-Hydroxy-1-phenylimidazolidine-2-thione as a new amidoalkylating agent for heterocyclic compounds

Russian Chemical Bulletin - We showed a possibility of using 5-hydroxy-1-phenylimidazolidine-2-thione as an amidoalkylating agent in the reactions with 1-methyloxindole, 3-pyrazolone, and pyrazole...     

Hetarylpyrazoles. II. Reactions of pyrazol-l'-ylpyridines

Pyrazol-l'-ylpyridines undergo electrophilic substitution reactions (bromination, chlorination, and nitration) preferentially in the pyrazole ring. There is some evidence of the mutual influence of the pyrazole and the pyridine ring on the reactivity of the system. Some modifications of the substituents were also carried out. A dihydro derivative of a new ring system, pyrazolo[1′,2′-a]pyrido[2,1-c][l,2,4]triazine was also obtained.