Alkylation and Reduction of N-Alkyl-4-nitroindazoles with Anhydrous SnCl2 in Ethanol: Synthesis of Novel 7-Ethoxy-N-alkylindazole Derivatives

Rakib, El Mostapha; Abbassi, Najat; Hannioui, A.; Alaoui, Mdaghri; Benchidmi, M.; Essassi, El Mokhtar; Geffken, Detlef

doi:10.3987/com-11-12149

Cited by 19 publications

(6 citation statements)

References 22 publications

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“…In a previous study performed with 4-nitroindazole 1a at low temperature (0 °C), only the substituted compounds 2a and 4a were obtained in a total yield of 58% [39]. Therefore, the elimination process with higher activation energy than the substitution route [42] is favoured by the higher temperature used in the reactions reported in the present work.…”

Section: Introductionmentioning

confidence: 54%

“…The annular tautomerisation of two nitrogen atoms (N-1, N-2) present in the indazole ring, has been explored in synthetic and theoretical studies concerning the substitution of N-H-indazole [38]. More recently, it was reported by our group that the reactivity of N-1 and N-2 alkylated indazole isomers is strongly dependent on the reaction conditions, namely, solvent proticity and pH, as well as, electronic and steric effects [39,40].Herein it is described the synthesis of a series of N-bromoethyl-nitroindazoles and N-vinyl-nitroindazoles reacting the corresponding nitroindazoles with 1,2-dibromoethane. A detailed analysis of the reaction conditions allowed to develop a simple, fast and inexpensive protocol to obtain both the vinyl and the bromoethyl derivatives in just one step in reasonable amounts.…”

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A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions

et al. 2019

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The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N-(2-bromoethyl)and N-vinyl-nitro-1H-indazoles. The Cu(I)-catalysed azide-alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N-(2-bromoethyl)nitroindazoles into the corresponding azide. The reactivity in 1,3-dipolar cycloaddition reactions with nitrile imines generated in situ from ethyl hydrazono-α-bromoglyoxylates was studied with nitroindazoles bearing a vinyl unit. The corresponding nitroindazole-pyrazoline derivatives were obtained in good to excellent yields.Molecules 2020, 25, 126 2 of 18 antipyretic, antioxidant, antiparasitic, antimicrobial, antitumoral and anti-inflammatory activities, among others [5][6][7][21][22][23].Indazoles are another important group of N-heterocycles with significant biological activities as nitric oxide synthase (NOS) inhibitors, kinase inhibitors, anti-inflammatory, anticancer, antimicrobial, antifungal, antimalarial, and antileishmanial agents, among others.Some anticancer and anti-inflammatory drugs based in indazole scaffolds are commercially available [24][25][26][27][28][29][30]. Besides the biological properties presented by indazole derivatives, this family of N-heterocycles also showed potential to be used in other fields as corrosion inhibitors, components for OLEDs and battery applications, and as copolymerizing molecules for new materials [31][32][33][34].Following our interest on developing synthetic approaches to functionalize the indazole core [35,36], we decided to follow the 1,3-dipolar cycloaddition methodology to substitute nitroindazoles with triazole or pyrazoline moieties, aiming in such way to obtain new compounds with improved biological features for different applications. In the strategy envisaged it was considered that the alkylation of indazole with 1,2-dibromoethane using liquid-liquid phase transfer catalysis, could afford not only the N-1and N-2-bromoethylindazoles, but also the corresponding N-1and N-2-vinylindazoles [37]. The annular tautomerisation of two nitrogen atoms (N-1, N-2) present in the indazole ring, has been explored in synthetic and theoretical studies concerning the substitution of N-H-indazole [38]. More recently, it was reported by our group that the reactivity of N-1 and N-2 alkylated indazole isomers is strongly dependent on the reaction conditions, namely, solvent proticity and pH, as well as, electronic and steric effects [39,40].Herein it is described the synthesis of a series of N-bromoethyl-nitroindazoles and N-vinyl-nitroindazoles reacting the corresponding nitroindazoles with 1,2-dibromoethane. A detailed analysis of the reaction conditions allowed to develop a simple, fast and inexpensive protocol to obtain both the vinyl and the bromoethyl derivatives in just one step in reasonable amounts. One of the bromoethyl derivatives was used to afford the corresponding azide, and its reactivity in CuAAC reactions with different...

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Section: Introductionmentioning

confidence: 54%

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A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions

et al. 2019

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“…Compound 5 a – i formation is supported by a combination of reactions and characterization data detailed in the synthesis process. Spectroscopy studies, including techniques like NMR, IR, and mass spectrometry, provide crucial insights into the compound‘s structural confirmation and purity [53–58] …”

Section: Resultsmentioning

confidence: 99%

Exploration of N‐(6‐Indazolyl) benzenesulfonamide Derivatives as Potential Antioxidants and Antimicrobial Agents: Integrating Synthesis, In Silico Docking, and Bioactivity Profiling

Yadav,

Rao,

Kumar

et al. 2023

ChemistrySelect

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A new series of N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl) benzenesulfonamide derivatives (4 a–i) and N‐(1‐(2‐chloropyrimidin‐4‐yl)‐6‐ethoxy‐1H‐indazol‐5‐yl) benzenesulfonamide derivatives (5 a–i) was synthesized via reduction of 1‐(2‐halopyrimidin‐4‐yl)‐5‐nitro‐1H‐indazole (3) with SnCl2 followed by reaction with various aryl sulphonyl chlorides in pyridine. The structures were confirmed using IR, 1H‐NMR, 13C‐NMR, and mass spectral methods. Compounds 4 a–i and 5 a–i were evaluated for antifungal and antibacterial activities against Gram‐negative and Gram‐positive bacteria. They also exhibited antioxidant potential in DPPH (IC50=0.094‐0.467 μmol/ml) and ABTS assays (IC50=0.101–0.496 μmol/ml). Remarkably, N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐2‐nitrobenzenesulfonamide displayed the highest antibacterial activity, while N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐4‐methoxybenzenesulfonamide showed excellent antifungal potential. Compound N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐2‐nitrobenzenesulfonamide exhibited the most significant antioxidant activity. In this study, molecular dynamics simulations were utilized to rigorously examine the stability of ligand‐protein complexes, demonstrating a consistent and robust binding of the most potent compound within the target proteins′ binding sites. Computational assessments were further employed to predict the drug‐likeness and ADMET properties of the synthesized compounds. The results unequivocally confirmed the remarkable antioxidant and antimicrobial potential of all derivatives, a finding substantiated by comprehensive molecular docking analyses that revealed intricate interactions involving hydrogen bonds, electrostatic forces, and hydrophobic contacts. These findings collectively provide invaluable insights into the complex molecular structure and receptor target site dynamics, laying a strong foundation for the development of novel active antioxidant and antimicrobial agents with promising pharmaceutical implications.

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“…The starting materials and products 1, [30] 1’, [36] 5 , [21] 6 [37] , 10 [32] and 11 [32] were prepared as described in the literature.…”

Section: Supporting Informationmentioning

confidence: 99%

Palladium‐Catalyzed Site‐Selective C7 Oxidative Arylation of 4‐EWG‐1H‐Indazoles

Ouazzani Chahdi,

Boujdi,

El Brahmi

et al. 2023

Asian J Org Chem

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An efficient palladium‐catalyzed oxidative arylation of substituted 1H‐indazole with various arenes and heteroarenes as coupling partners is reported. A site selective C7 oxidative arylation was perfectly achieved with a directing electron‐withdrawing groups (EWG) located at the C4 position of the 1H‐indazole. The desired products are obtained in moderate to good yields from 4‐NO2 or 4‐CO2Me 1H‐indazoles and various (hetero)aryls as coupling partners in the presence of Pd(OAc)2 as catalyst, phenanthroline as ligand, Ag2CO3 as oxidant and NaOH as the base. Density functional theory was also conducted for reaction mechanism comprehension. This approach provides a highly effective, direct, and atom economical way to build C7‐ (het)arylated 1H‐indazole compounds.

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Alkylation and Reduction of N-Alkyl-4-nitroindazoles with Anhydrous SnCl2 in Ethanol: Synthesis of Novel 7-Ethoxy-N-alkylindazole Derivatives

Cited by 19 publications

References 22 publications

A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions

A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions

Exploration of N‐(6‐Indazolyl) benzenesulfonamide Derivatives as Potential Antioxidants and Antimicrobial Agents: Integrating Synthesis, In Silico Docking, and Bioactivity Profiling

Palladium‐Catalyzed Site‐Selective C7 Oxidative Arylation of 4‐EWG‐1H‐Indazoles

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