Practical synthesis of bicyclic pyrazol-5-one derivatives

This communication describes a convenient synthesis of fused bicyclic pyrazolones in a one-pot reaction procedure. Modified protocols are also developed to access 5,5-bicyclic and bulky pyrazolones in good yields. The method reported herein represents a practical approach to structurally diversified bicyclic pyrazolones.     

Synthesis of a novel pentacycle: 8-Methyl-10-phenylpyrazolo[4′,3′: 5,6]-pyrano[3,2-c]-[1,10]phenanthrolin-7(10H)-one

The title compound — a derivative of a hitherto unknown pentacyclic ring system — results from the reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one and 4-chloro-1,10-phenanthroline-3-carbonyl chloride in the presence of Ca(OH)₂ in boiling 1,4-dioxane. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 884–890, June, 2008.     

Solid‐State Photochromic Behavior and Thermal Bleaching Kinetics of Two Novel Pyrazolone Phenylsemicarbazones

Two novel photochromic compounds, 1,3‐diphenyl‐4‐benzal‐5‐hydroxypyrazole 4‐phenylsemicarbazone ( 1 a ) and 1,3‐diphenyl‐4‐(4‐nitrobenzal)‐5‐hydroxypyrazole 4‐phenylsemicarbazone ( 2 a ), are synthesized and characterized by elemental analysis, mass spectrometry, FTIR spectroscopy, and ¹H NMR spectroscopy. Their properties, including photochromic behavior, fluorescence properties, and thermal bleaching kinetics, are investigated. The results show that the two compounds exhibit improved photochromic performance in coloration and thermal bleaching rates, excellent photostability, high fatigue resistance, and reversible fluorescence switching properties in the solid state in comparison to reported pyrazolone thiosemicarbazones. The thermal bleaching process obeys first‐order kinetics. Bleaching of powders at 130 °C is completed within 90 s for 1 b (the colored isomer of 1 a ) and 150 s for 2 b (the colored isomer of 2 a ). The activation energy for the thermal bleaching process is determined to be 69 and 95 kJ mol^?1, with frequency factors of 9.5×10⁷ and 9.4×10¹⁰ s^?1 for 1 b and 2 b , respectively.     

Experimental and Theoretical DFT Investigations in the [2,3]-Wittig-Type Rearrangement of Propargyl/Allyl-Oxy-Pyrazolones

Here we report the synthesis of interesting 3-alkyl-4-hydroxy-1-aryl-4-(propa-1,2-dienyl)1H-pyrazol-5(4H)-ones and 9-alkyl-7-aryl-1-oxa-7,8-diazaspiro[4.4]nona-3,8-dien-6-ones, starting from 1,2-diaza-1,3-dienes (DDs) and propargyl alcohol. The reaction proceeds through a sequence Michael-type nucleophilic attack/cyclization/[2,3]-Wittig rearrangement. In the same way, the reaction between the aforementioned DDs and allyl alcohol furnished 4-allyl-4-hydroxy-3-alkyl-1-aryl-1H-pyrazol-5(4H)-ones. A DFT study was also carried out, in order to have decisive clarifications about the mechanism.     

Synthesis, structures, and spectral properties of biomimetic azomethine metal chelates with chromophores CuN2S2, CuN2O2, and CuN2Se2. Crystal structure of bis[4-(benzyl)aldimino-3-methyl-1-phenyl-5-pyrazolothiolato]copper(II)

Copper(II) chelates of composition CuL₂ were synthesized based on 4-aminomethylene derivatives of 5-thiopyrazoles (LH). The complexes were studied by UV, IR, ESR, and EXAFS spectroscopy, magnetochemistry, and X-ray diffraction analysis. The coordination polyhedra in the complexes are pseudotetrahedra or octahedra of the types CuN₂S₂ or CuN₄S₂, respectively, which are distorted due to the Jahn—Teller effect. The UV and ESR spectra of copper chelates with a six-coordinate metallocycle formed by the N and S atoms of the azomethine ligand and the nitrogen atom of the quinoline substituent (R) of the C=N−R fragment are most similar to the spectra observed for metals involved in the active centers of natural metalloenzymes (“blue” copper proteins). Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1891–1896, November, 2000.     

Regioselective Synthesis of 5- and 3-Hydroxy-N-Aryl-1H-Pyrazole-4-Carboxylates and Their Evaluation as Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

In silico evaluation of various regioisomeric 5- and 3-hydroxy-substituted alkyl 1-aryl-1H-pyrazole-4-carboxylates and their acyclic precursors yielded promising results with respect to their binding in the active site of dihydroorotate dehydrogenase of Plasmodium falciparum (PfDHODH). Consequently, four ethyl 1-aryl-5-hydroxy-1H-pyrazole-4-carboxylates and their 3-hydroxy regioisomers were prepared by two-step syntheses via enaminone-type reagents or key intermediates. The synthesis of 5-hydroxy-1H-pyrazoles was carried out using the literature protocol comprising acid-catalyzed transamination of diethyl [(dimethylamino)methylene]malonate with arylhydrazines followed by base-catalyzed cyclization of the intermediate hydrazones. For the synthesis of isomeric methyl 1-aryl-3-hydroxy-1H-pyrazole-4-carboxylates, a novel two-step synthesis was developed. It comprises acylation of hydrazines with methyl malonyl chloride followed by cyclization of the hydrazines with tert-butoxy-bis(dimethylamino)methane. Testing the pyrazole derivatives for the inhibition of PfDHODH showed that 1-(naphthalene-2-yl)-5-hydroxy-1H-pyrazole-4-carboxylate and 1-(naphthalene-2-yl)-, 1-(2,4,6-trichlorophenyl)-, and 1-[4-(trifluoromethyl)phenyl]-3-hydroxy-1H-pyrazole-4-carboxylates (~30% inhibition) were slightly more potent than a known inhibitor, diethyl α-{[(1H-indazol-5-yl)amino]methylidene}malonate (19% inhibition).     

Mn(III) mixed‐ligand complexes with bis‐pyrazolones and ciprofloxacin drug: synthesis,characterization and antibacterial activities

The fluoroquinolone family member ciprofloxacin is well known for its drug design and coordinating ability towards metal ions. The coordination chemistry of this drug with metal ions of biological and pharmaceutical importance is of considerable interest. Novel Mn(III) mixed‐ligand complexes of ciprofloxacin with various bis‐pyrazolone‐based dinegative bidentate ligands were synthesized and characterized on the basis of their physical properties, magnetic susceptibility measurements, (FT‐IR and electronic) spectral studies. The FAB‐mass spectrum of [Mn(A⁹)(L)(H₂O)₂]·H₂O [where H₂A⁹ = 4,4′‐(p‐tolylmethylene)bis(3‐methyl‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐5‐ol) and HL = 1‐cyclopropyl‐6‐fluoro‐4‐oxo‐7‐(piperazin‐1‐yl)‐1,4‐dihydroquinoline‐3‐carboxylic acid] was determined. All the synthesized compounds were screened for their bioactivity. The mixed‐ligand complexes exhibited comparable activities against two Gram‐negative (Escherichia coli and Serratia marcescens) and two Gram‐positive (Staphylococcus aureus and Bacillus subtilis) microorganisms. Copyright © 2011 John Wiley & Sons, Ltd.     

Asymmetric Synthesis of Spiropyrazolones by Sequential Organo‐ and Silver Catalysis

A stereoselective one‐pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia‐ene reaction has been developed. Depending on the nitroalkene, the 5‐exo‐dig‐cyclization could be achieved by silver‐catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments.     

Base-Catalyzed Synthesis of Spiropyrazoloaminonitriles with Arylidene Pyrazolone and Vinylogous Malononitriles through a Cascade Michael Addition and Cyclization

Synthesis of title compounds were accomplished by a reaction of vinyl malononitriles and arylidene pyrazolones catalyzed by base. This protocol proceeds via Michael addition followed by intramolecular cyclization leading to the formation of two new C−C bonds. Further the same reaction was also conducted with α,α-dicyano olefins and vinyl malononitriles to furnish 1,6-dihydro biphenyl compounds. Simple reaction conditions, high yields and compatibility are the advantages of this protocol.