Preparation of polymer-bound pyrazolone active esters for combinatorial chemistry

The preparation of solid-phase active esters from a new pyrazolone linker resin is described. N-Acylation using this resin provides various amide products with a high conversion rate and good purity under mild conditions. The polymer-bound pyrazolone linkers are stable in the reaction conditions and are resistant to hydrolysis. Moreover, this resin can also be reused repeatedly without a loss of reactivity.     

酰代呲唑酮作为金属元素萃取剂的研究(Ⅱ)——不同基团取代的呲唑酮对于铈(Ⅲ)的萃取及其与二辛基亚砜的协同萃取作用

本文研究了不同基团取代的酰代吡唑酮对铈(Ⅲ)的萃取。采用斜率法和同位素示踪技术,测得它们在HCl和HNO₃体系中的萃合物组成和萃取平衡常数;还研究了它们与二辛基亚砜对铈(Ⅲ)的协同萃取。研究过程中,以HTTA作为对照。     

Catalytic Asymmetric Synthesis of Spiropyrazolones and their Application in Medicinal Chemistry

Chiral spiropyrazolones are unique frameworks widely found in a large family of medicinally relevant compounds with various biological activities. Substantial research efforts have been invested toward stereoselectively by constructing spiro‐cyclic structures. Over the past years, remarkable progress has been made in the organo‐ and metal‐catalyzed asymmetric synthesis of spiropyrazolones through the utilization of accessible simple pyrazolone derivatives as raw materials. This review is organized according to the size of the spiro‐ring fused at the 4‐position of the pyrazolone framework. In the last part, the bio‐evaluations of chiral spiropyrazolones for drug discovery are summarized.     

Efficient Synthesis,Characterization, In Vitro Antibacterial and Antifungal Activity Study and Computational Tool for Prediction of Molecular Properties of Some Novel Schiff's Base via Betti's Protocol and Azetidinones

Series of new substituted pyrazolone derivatives via Betti's condensation reaction of pyrazolone and different aldehydes has been reported successfully under ambient reaction conditions. The structural elucidation of newly synthesized compounds was done using analytical and spectroscopic tools such as elemental analysis, ¹H NMR, ¹³C NMR, and mass spectroscopy. Physicochemical parameters, toxicity profiles and drug likeness properties were studied using various bioinformaticals tools like Osiris and molinspiration. These results viz., the good correlations between the inhibitory activities and the computational values make the molecules available for future protein–ligand interaction studies. It further provided useful information in understanding the structural and chemical features of the drug in designing and finding new potential inhibitors.     

Reaction of acridine with pyrazolone derivatives

A mixture of acridine and a pyrazolone derivative was reacted in the solid state (without solvent). It is proposed that the enol tautomer (the C4‐position) of the pyrazolone derivative attacks the C9‐position of acridine through a nucleophilic reaction resulting in products where the C4‐position of pyrazolone is connected to the C9‐position of acridine. When the reaction of 3‐methyl‐1‐phenyl‐5‐pyrazolone and acridine was carried out at low temperature (25°–50°), the reaction product was obtained even when the majority of the reaction mixture had not melted. The same reaction was also carried out in the presence of an ultrasonic wave at same temperature (25°–50°) and the reaction product was obtained in high yield. Under ultrasonic conditions, the reaction mixture was not melted. However, the interface between 3‐methyl‐1‐phenyl‐5‐pyrazolone and acridine gradually changed from white to black. In this reaction, the dihydroacridine dimer is not obtained.     

Heterodiene syntheses—XIII: The stereochemical consequences of electronic and steric interactions in the transition state of the cycloaddition between 4-arylidene-5-pyrazolones and vinylethers

The competition between exo and endo transition states in the cycloaddition of 4-arylidene-5-pyrazolones and vinylethers is rationalized in terms of steric and electronic interactions.The steric interactions depend mainly upon the requirements of the substituent in position 3 of the starting pyrazolone.The electronic factors are rationalized in terms of secondary non-bonding interactions between the HOMO of the vinylether which acts as donor and the LUMO of the pyrazolone which acts as acceptor.An E configuration of the pyrazolone is suggested as “reacting” species.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Uncatalysed Knoevenagel condensation in aqueous medium at room temperature

Knoevenagel condensation of various aromatic and heteroaromatic aldehydes with active methylene compounds like malononitrile, ethyl cyanoacetamide, ethyl cyanoacetate, barbituric acids, Meldrum’s acid, dimedone and pyrazolone proceeds smoothly with stirring in an aqueous medium. The reactions occur at room temperature giving excellent yields of the products. The work-up procedure is very simple and the products do not require further purification.     

CsF promoted rapid synthesis of spirooxindole-pyran annulated heterocycles at room temperature in ethanol

A newer, versatile, and straightforward synthetic strategy for the construction of functionalized spirooxindole-pyran annulated heterocycles is described. The procedure is based on CsF-promoted rapid tandem Knoevenagel-Michael-Cyclocondensation reaction of isatin, malononitrile, and 4-hydroxycoumarin/barbituric acids/pyrazolone at room temperature in ethanol. This methodology has various advantages like easy operational, excellent yields within short reaction time (3-25 min), and simple isolation of products. The CsF has a dual role as a base and carbonyl activator.     

A study of the fluorescence of some newly synthesized europium complexes with pyrazolone derivatives

Some europium complexes with pyrazolone derivatives and 1,10-phenanthroline were synthesized and characterized. The europium ion was found to coordinate to O atoms of the pyrazolone derivatives and to N atoms of 1,10-phenanthroline. A strongly ligand-localized UV absorption leads to the europium-centered emissions between 580 and 750 nm which were assigned as the 5D0-->7F0,1,2,3,4 and 5D1-->7F3,4 transitions. A low site symmetry for the Eu3+ ion was confirmed from the observation of 5D0-->7F0 emission and from the splitting of the other bands. In contrast to many Eu complexes that have been investigated a rather weak emission was measured by introduction of a Schiff base to form a ternary complex with the pyrazolone derivative. The long fluorescence lifetimes of these complexes suggest an energy transfer process from ligands to Eu3+ ion through the triplet state of the ligands.     

An Efficient One‐pot Synthesis of Pyrazolone Derivatives Promoted by Acidic Ionic Liquid

A new class of pyrazolone derivatives has been isolated in good to excellent yields from the 2:1 condensation reaction between 3‐methyl‐1‐phenyl‐5‐pyrazolone and arylaldehydes in the presence of ionic liquid [HMIM]HSO₄. The compounds were characterised by their IR, NMR spectra, MS and elemental analyses. The important features of the methodology are a wide application range of substrates, higher yields and shorter reaction time.     

Synthesis and Characterization of Phenylene‐bis‐pyrazolones and Nitrosation Derivatives

Phenylene bis‐pyrazolone derivatives were obtained by condensation of two aromatic β‐diketo diesters with methyl‐, 2‐hydroxyethyl‐ and phenylhydrazines. The pyrazolone rings are connected to the central benzene ring by their C‐3 , leaving C‐4 free for further derivatization. Thus, and despite their low solubility, these compounds were successfully nitrosated in good yield providing new chelating dioximes.     

Synthesis of 1‐(p‐Sulphophenyl)‐3‐methyl‐5‐pyrazolone Based Acid Dyes and Their Applications on Leather

A new series of pyrazolone based azo acid dyes (3a–g) has been synthesized starting from 1‐(p‐sul‐phophenyl)‐3‐methyl‐5‐pyrazolone (1). The synthetic methodology included the nitrosation of p‐sulphophenyl methyl pyrazolone followed by reduction, diazotization and coupling with Naphthol AS derivatives (2a–f), in alkaline medium to yield different acid dyes. Multichromic metal complexes of these dyes (5a–f, 6a–f and 7a–f) with 3d transition metals Chromium, Iron and Copper were also synthesized. The structures of all of newly synthesized compounds were confirmed by analytical data and spectroscopic techniques. The synthesized dyes were applied on leather to assess their light fastness, wash fastness and rubbing fastness and were shown to exhibit high values of 4–5 for majority of dyes.     

Identification of conjugated metabolites of pyrazolone drugs in human urine by pyrolysis-mass spectrometry

It is shown that a combination of pyrolysis electron ionization and soft ionization mass spectrometry represents a direct approach for the elucidation of the complex biotransformation pattern of two pyrazolone analgesics, antipyrine and dipyrone. In a first screening procedure crude extracts from biological material can readily be utilized. Urinary conjugates of structural hydroxy isomers formed from antipyrine can be differentiated by specific thermolytic reactions of the pyrazolone moiety. As a rule, sulpho conjugates are found to exhibit a lower stability against thermal stress than the corresponding gluco conjugates. Using this integrated mass spectrometric approach, investigation of the phase II metabolism of dipyrone succeeded in identifying five unknown metabolites.     

Crystal Structure of 8,9-Dimethoxy-5,5-dimethyl-2,3,5,6-tetrahydro-3-oxopyrazolo[3,4-b]benzo-3-azepine

The crystal structure of 8,9-dimethoxy-5,5-dimethyl-2,3,5,6-tetrahydro-3-oxopyrazolo[3,4-b]benzo-3-azepine is determined by X-ray diffraction analysis. The molecule crystallizes in the form of an isomer with the hydrogen atom at the nitrogen atom in position 2 of the pyrazolone fragment. The electron density is localized over the multiple bonds N(1)=C(12) (1.253(5) Å) of the azepine cycle and N(2)=C(1) (1.302(4) Å) of the pyrazolone cycle.     

The solid-state michael addition of 3-methyl-1-phenyl-5-pyrazolone

A novel solid-state Michael addition between pyrazolone 1 and 4-arylidenepyrazolones 2 at ambient temperature produced Michael adducts, 4,4′-arylidenebis(3-methyl-1-phenyl-5-pyrazolones) 3. Pyrazolones 3 formed salts 4 with Cu²⁺ in solution, indicating the enolic structure of the pyrazolone rings. The reactivity of 2 with 1 is discussed in terms of the electronic and steric effects of the substituent on the arylidene group of compounds 2 . Pyrazolone 1 also underwent the solid state Michael addition reaction with maleimide at 100° to give the adducts 7,8 and 9 .     

Investigation of interaction strategies between pyrazolone dyes and poly(acrylamide-co-acrylic acid)

The removal of dyes from waste water before their discharge into aquatic ecosystems is of substantial concern. Amongst functional macromolecules, the combination of polymers with dyes is a research field of enormous potential with regard to high-performance materials. The present study investigates interactions strategies between P(AM-co-AA) polymer with pyrazolone azo dyes in water as green solvent. These interactions were confirmed by FTIR spectroscopy, Ultra-visible spectroscopy, EDAX analysis, and FE-SEM analysis. Polymer P(AM-co-AA) has porous structure in which dyes present in the water get absorb hence it is use to remove pyrazolone dyes from water.

     

Cyclization of pyrazolones: novel synthesis of pyrano,pyrido, pyrimido and spiropyrazole derivatives

Depending on the reaction conditions, two alternative cyclizations are possible for [3?+?3] cyclocondensation of pyrazolone derivative 1a and ethyl cyanoacetate of type pyrano [2,3-c] pyrazol-6(1H)-one 2 and pyrano [2,3-c] pyrazol-4(1H)-one 3. Keeping of enaminic system 3 and benzylidene malononitrile in the presence of catalytic amount of trimethylamine resulted in pyridine cyclization affording pyrazolopyranopyridine derivative 4, not 5. The pyrazolone derivative 6a was obtained as a result of the acid-mediated addition reaction between compound 1a, urea and/or ammonium thiocyanate. In addition, the bispyrazolone of type 6b was obtained from the condensation reaction of urea and pyrazolone derivative. The spiro compound 7 was obtained from the double-addition reaction of pyrazolone to cinnamoyl isothiocyanate. A one-pot three-component condensation of a 3-hydroxybenzaldehyde, pyrazolone 1a, urea and/or thiourea under Biginelli conditions resulted in tetrahydropyrazolo pyrimidine derivatives 8a and 8b, respectively. The acid-mediated reaction of benzaldehyde and pyrazolone derivative 1a in the presence of Ac₂O yielded styrylpyrazole derivative 9. The polyfunctionalized product 9 reacted with hydrazine to furnish pyrazolotriazoloe of type 10. Treatment of styrylpyrazole derivative 9 with aniline furnished the aniline derivative 11 and none of the expected polyheterocyclic derivative 12 was obtained. Compound 9 undergoes pyridine cyclization to produce 13 under the effect of urea. N-phenyl pyrazolone converted into pyrano-dipyrazolone derivative 14. Pyran of type 14 underwent a ring transformation upon treatment with urea and/or thiourea to give the same dipyrazolo pyrimidine derivative 15. The newly synthesized compounds were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, ESI/LC-MS and elemental analysis.     

A facile,catalyst-free synthesis of new polycyclic pyrrolo[1,2-b]pyrazolone derivatives

A convenient and efficient procedure has been developed for the synthesis of a new ring system, pyrrolo[1,2-b]pyrazolone, via two-component coupling reaction followed by base mediated intramolecular cyclization. Single-pot synthesis replacing the two step process has also been successfully carried out. A series of polycyclic pyrrolo[1,2-b]pyrazolone derivatives have been obtained by employing the procedure along with some fused pyrrol-1-ylamine system. The products were formed very rapidly in catalyst free condition in a good yield (up to 75%) and also it had tolerance to a wide scope of substrates.     

Metal-free synthesis of chromeno[4,3-c]pyrazol-3(2H)-one derivatives

An unprecedented metal-free synthesis of 4-(methylthio)chromeno[4,3-c]pyrazol-3(2H)-one is reported via sequential one-pot desulfitative [5+1] hetero-annulation. The present strategy consists of one-pot sequential, base catalysed dithioketene formation from active methylene of pyrazolone followed by methylation and [5+1] heteroannulative cyclization. The resulting substrate undergoes facile nucleophilic substitution with various amines to yield 4-(substituted-amine)-chromeno[4,3-c]pyrazol-3(2H)-one derivatives under metal free condition.