Functionalized Pyrazoles Research Articles

Synthesis, Insecticide Evaluation & Molecular Docking Studies of Some New Functionalized Pyrazole Derivatives Against the Cotton Leafworm, Spodoptera littoralis.

5-(Cyanomethyl)-3-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino)-1H-pyrazole-4-carbonitrile (3) is used as a key for the synthesis of arylidenes 5 a-fvia its reaction with some aldehydes 4 a-f. 5-[(5,5-Dimethyl-3-oxocyclohex-1-en-1-yl)amino]-3-(2-imino-2H-chromen-3-yl)-1H-pyrazole-4-carbonitrile (7) was synthesized via the reaction of compound (3) with 2-Hydroxybenzaldehyde in EtOH/piperidine. The target compounds were tested against cotton leafworm larvae in their second and fourth instar. The available data demonstrated that the LC50 values for commercial phenylpyrazole were 3.37 mg/L and 4.55 mg/L for the most affected synthesized compound, 5 b. The chemical structure of compound 5 bhas two cyano moieties, a pyrazole ring and a chlorophenyl, which may be increasing it efficiency. Evaluation of the latent effects of the examined synthesized compounds on various biological parameters, including adult longevity, pupal weight, proportion of normal, deformed pupae, adult emergency, fecundity, and egg hatchability, was done in an additional effort to slightly improve insecticidal compounds. Seven target synthesized compounds were subjected to a molecular docking analysis against glutamate-activated chloride channels. Twelve artificial compounds with the PDB ID of 4COF were subjected to a molecular docking study against the gamma-aminobutyric acid receptor (GABA).

Quadruple Functionalized Pyrazole Pharmacophores by One-pot Regioselective [3+2] Cycloaddition of Fluorinated Nitrile Imines and Dicyanoalkenes.

Here we present a quadruple functionalization approach for the modular construction of fully substituted N1 -aryl 3-di/trifluoro-methyl-4/5-cyanopyrazole pharmacophores from readily available hydrazonyl chlorides and dicyanoalkenes. The realization of this [3+2] cycloaddition reaction hinges upon the employment of N-aryl di/trifluoromethyl nitrile imines as the 1,3-dipoles to bypass external synthetic steps and dicyanoalkenes as the dipolarophiles to tune the regioselectivity. This one-pot strategy offers access to a divergent library of cyano analogues of prevalent 3-di/trifluoromethyl pyrazole pharmacophores, among which several compounds have shown potent inhibitory activity towards cyclooxygenase 2 (COX-2) compared with marketed drug Celecoxib.

One-Pot Synthesis and Antiproliferative Activity of Highly Functionalized Pyrazole Derivatives.

A series of highly functionalized pyrazole derivatives has been prepared by a one-pot, versatile and regioselective procedure. Pyrazoles 1-29 were tested in cell-based assay to assess their antiproliferative activity against a panel of tumour cells. Additionally, the cytotoxicity of prepared compounds was evaluated against normal human fibroblasts. The antiproliferative activity of the synthesized molecules emerged to be affected by the nature of the substituents of the pyrazole scaffold and derivatives 21-23 proved to inhibit the growth of melanoma and cervical cancer cells. Compound 23 was identified as the most active derivative and docking simulations predicted its ability to interact with estrogen receptors.

Regioselective Synthesis of Highly Functionalized Pyrazoles from N-Tosylhydrazones.

A regioselective synthesis of highly functionalized pyrazoles from N-tosylhydrazones was developed. The reaction was general for a wide range of substrates and demonstrated excellent tolerance to a variety of substituents, and the method has been successfully applied to the formal synthesis of ibrutinib.

A catalyst- and solvent-free protocol for the sustainable synthesis of fused 4H-pyran derivatives.

An efficient and cost-effective method was developed for the synthesis of two kinds of fused 4H-pyran derivatives, namely, dihydropyrano[2,3-c]pyrazole 4 and pyrano[3,2-c]chromenone 6. The reactions of 3-methyl-1-phenyl-5-pyrazolone/4-hydroxycoumarin with aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), involving the Knoevenagel, Michael-addition, O-cyclization and elimination reactions under thermal heating, afforded the desired products. The synthesized compounds were characterized by standard spectroscopic techniques. Further, the structures of pyrazole-fused 4H-pyran 4a and coumarin-fused 4H-pyran 6b were confirmed by single-crystal XRD analysis. The short reaction time, good-to-excellent yields, elimination of the use of expensive, metallic and toxic catalysts or hazardous organic solvents and high atom-economy are some noteworthy features of this protocol.

Facile synthesis of novel α-methylene-pyrazole-carboxylate substituted imines and trans-β-lactams: Versatile synthons for diverse heterocyclic molecules

ABSTRACTA simple, facile, and high yielding stereoselective approach for the integration of α-methylene-pyrazole-carboxylates at the β-lactam nucleus is described. These monocyclic β-lactams have been synthesized by treatment of 2-phenoxy/benzylthio/phenylthio ethanoic acids or acetoxyacetyl chloride/phthalimidoacetyl chloride 5a–e with novel α-methylene-pyrazole-carboxylate imines 4a–c using Et3N and POCl3 in refluxing toluene. All of the newly synthesized α-methylene-pyrazole carboxylate imines 4a–c and their β-lactam derivatives 6a–h have been fully characterized by spectroscopic techniques such as FTIR, NMR (1H, 13C, and 13C DEPT-135), 2D-NMR (COSY and HSQC), and elemental analyses (CHN). The cycloaddition reaction was found to be highly stereoselective leading to the exclusive formation of trans-β-lactams 6a–h and trans configuration was assigned with respect to coupling constant values of C3-H and C4-H. The novel β-lactams 6a–h bearing α-methylene-pyrazole-carboxylate ring system will serve as useful synthons for highly functionalized acids, acetohydrazides/pyrazolones, alcohols, pyrazole carboxamides, peptides, and promising biologically active agents.

SYNTHESIS AND BIOLOGICAL EVALUATION OF 1,3,5-TRISUBSTITUTED PYRAZOLINES AS ANTIMALARIAL–ANTIMICROBIAL AGENTS

A convenient and efficient reaction of chalcone for the synthesis of highly functionalized pyrazole and pyridine has been developed. Many pieces of evidence point out the relevance of natural compounds for malaria and its prevention, including chalcones. Ring substituted quinolines are synthesized as the emerging class of antimalarial agents. Two series i.e. 4-(3-(substituted phenyl)-5-(2,6-dichloroquinolin-3-yl)-4, 5-dihydro-1H-pyrazol-1-yl)benzene sulfonamide (4a-4e) and [5-(2,6-dichloroquinolin-3-yl)-3-(substituted phenyl)-4,5-dihydro-1H-pyrazol-1-yl]pyridine-3-yl-methanone.(4a’-4e’) were synthesized. Above mentioned compounds were characterized by FTIR, 1H-NMR, 13C-NMR, mass spectrometry and elemental analysis. Attempt has been made to investigate the mechanism behind the formation of substituted quinolines. All the synthesized substituted quinolines have shown moderate to good antimalarial activity and good antimicrobial activity against bacterial and fungal strains. Compounds 4a and 4d’ were found to be the candidate compounds to investigate further for its potential antimalarial and antimicrobial activity.

ChemInform Abstract: Atmospheric Oxygen Mediated Synthesis of Pyrazole under Visible Irradiation.

AbstractAn eco‐efficient, clean, and photoredox catalyzed synthesis of highly functionalized pyrazole derivatives in good to excellent yields is reported.

ChemInform Abstract: An Efficient One Pot Regioselective Synthesis of a 3,3′‐Spiro‐phosphonylpyrazole‐oxindole Framework via Base Mediated [1,3]‐Dipolar Cycloaddition Reaction of the Bestmann—Ohira Reagent with Methyleneindolinones.

A one pot, highly regioselective synthesis of racemic 3,3′-spiro-phosphonylpyrazole-oxindole by 1,3-dipolar cycloaddition of an in situ generated anion of dialkyl 1-diazomethylphosphonate from the Bestmann–Ohira reagent (BOR) & methyleneindolinones has been developed. The synthesis affords the highly functionalized pyrazole scaffolds in good yields with excellent regioselectivity under mild reaction conditions within a short reaction time.

ChemInform Abstract: Enantioselective Synthesis of Functionalized Pyrazoles by NHC‐Catalyzed Reaction of Pyrazolones with α,β‐Unsaturated Aldehydes.

AbstractConditions for the reaction of 3‐aryl, alkyl, or arenyl 1‐tert‐butyl‐4,5‐dihydro‐1H‐pyrazol‐5‐ones with 3‐aryl or 3‐alkyl propenals to form pyranone‐fused pyrazoles are developed, and the products are obtained with high yields and high enantioselectivities.

ChemInform Abstract: Synthesis of Polysubstituted Pyrazoles by a Platinum‐Catalyzed Sigmatropic Rearrangement/Cyclization Cascade.

AbstractThe method tolerates various functional groups, thus offering a convenient access to highly functionalized pyrazoles including medicinally relevant 3‐trifluoromethyl substituted derivatives [cf.

Synthesis of polysubstituted pyrazoles by a platinum-catalyzed sigmatropic rearrangement/cyclization cascade.

A highly efficient Pt-catalyzed [3,3] sigmatropic rearrangement/cyclization cascade of N-propargylhydrazones is reported. The process provides expedient access to a variety of highly functionalized pyrazoles. The substrate has good substituted group compatibility, and the bioactive 3-CF3 pyrazoles could be synthesized easily with this method.

ChemInform Abstract: Functionalized Pyrazoles as Agents in C—C Cross‐Coupling Reactions.

ChemInform Abstract: Functionalized Pyrazoles as Agents in C—C Cross‐Coupling Reactions.

Reactions of vinyl sulfone with α-diazo-β-ketosulfone and Bestmann–Ohira reagent for the regioselective synthesis of highly functionalized pyrazoles

The 1,3-dipolar cycloaddition of diazomethylsulfone anion, generated in situ from α-diazo-β-ketosulfone, with vinyl sulfone proceeds in a regioselective manner to provide sulfonylpyrazoles. Similar reaction of diazomethylphosphonate anion, derived from Bestmann–Ohira reagent, with vinyl sulfone leads to phosphonylpyrazoles. The sulfonyl group of vinyl sulfone undergoes chemoselective elimination in these reactions.

ChemInform Abstract: Tandem Synthesis of Highly Functionalized Pyrazole Derivatives from Terminal Alkynes, Sulfonyl Azides, Diethyl Azadicarboxylate, and Sodium Arylsulfinates.

AbstractThis is a one‐pot multicomponent reaction which yields either highly functionalized pyrazole derivatives or hydrazinedicarboxylates.

ChemInform Abstract: Synthesis of Ynone Trifluoroborates Toward Functionalized Pyrazoles.

AbstractCoupling of novel ynone trifluoroborates like (III) with hydrazines provides a new, efficient, and regioselective approach to pyrazole trifluoroborates as precursors of diverse pyrazole derivatives.

Synthesis of Ynone Trifluoroborates toward Functionalized Pyrazoles

The synthesis of a range of novel ynone trifluoroborates has been achieved, in a two-pot process from propargylic alcohols. These alkynes have been subsequently used in the formation of a range of pyrazole trifluoroborate salts via cyclization with hydrazines. The products are generated with high levels of regiocontrol and in excellent yields and represent versatile synthetic intermediates.

Tandem synthesis of highly functionalized pyrazole derivatives from terminal alkynes, sulfonyl azides, diethyl azadicarboxylate, and sodium arylsulfinates

The reaction between ketenimine intermediates [generated from terminal alkynes and sulfonyl azides], diethyl azadicarboxylate, and sodium arylsulfinates in N, N-dimethylformamide at room temperature, affords ethyl 2,3-dihydro-3-oxo-4-phenyl-2-tosyl-5-(tosylamino)pyrazole-1-carboxylates in moderate-to-good yields. When diisopropyl azadicarboxylate was used as the ester component, diisopropyl 1-arylsulfonyl-2-{[aryl(alkyl)sulfonyl]-2-phenylethanimidoyl}-1,2-hydrazinedicarboxylates were obtained.

ChemInform Abstract: Sc(OTf)3‐Catalyzed, Solvent‐Free Domino Synthesis of Functionalized Pyrazoles under Controlled Microwave Irradiation.

AbstractOptimized conditions are developed for the three‐component reaction to give highly functionalized pyrazoles for drug development.

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

The nitropolychlorobutadienes 3, 4 are valuable building blocks for various amination and successive heterocyclization products. Nucleophilic substitution reactions of the partially protected, bioactive amines 1, 2 with either vinyl, imidoyl or carbonyl chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succeeded. Deprotection of 21, 12 and 28 proved to be only partially feasible.