A convenient synthesis and structural analysis of novel 4,5,6,7-tetrahydro-1H-indazoles

Abstract

isopropyl esters has been synthesized by adopting a conventional method from cyclic -keto esters. 1 H, 13 C NMR, and IR spectra for all the compounds were investigated. HMBC, HSQC, COSY, and NOESY spectra of the representative compounds were studied. The stereochemistry of a six-membered ring of the fused indazoles resembled that of keto esters. From the HMBC correlations the indazole structure was confirmed as 1H-indazole.The universal requirements on heterocyclic compounds for their potential activities against microorganisms and significance in the pharmaceutical field prompted us to synthesize indazoles from cyclic keto esters. Several pathways have been described for the synthesis of indazoles [1][2][3][4][5].Recently we reported the synthesis and structural studies of r-2,c-4-bis(alkoxycarbonyl)-t-3-arylc-5-hydroxy-t-5-methylcyclohexanone by the condensation of acetoacetic esters with different aromatic aldehydes in the presence of methylamine [6][7][8]. The conformation of the two isopropyl groups of compound 1 was also studied with the help of X-ray crystallography of t-2-aryl-c-4-hydroxy-4-methyl-6-oxocyclohexane-r-1,c-3-dicarboxylic acid diisopropyl ester [9]. The present paper describes the use of the above compounds [8] assynthons for the preparation of 4,5,6,7-tetrahydro-1H-indazole. The synthesis of 4,5-trans-2-alkyl-4-hetaryl-5-ethoxycarbonyl(acetyl)-6-hydroxy-6-methyl-4,5,6,7-tetrahydro-2H-indazole has been reported [10]. Nevertheless, the published NMR spectral data apliesmoreto1H-indazolethan to 2H-indazole. N(2)-Substituted tetrahydroindazoles have been reported in [11].Synthesis of 4,5,6,7-1H-indazoles involves two steps. The first step, condensation of isopropyl acetoacetate with aromatic aldehydes in the presence of methylamine in ethanol, yielded cyclic -keto esters 1-7. They were treated with hydrazine hydrate in ethanol under reflux to give compounds 8-14 (Scheme). The mechanism of this second step was different from the expected one. Dehydration was faster than cyclization, and the cyclic intermediates formed in the reaction course were unstable and easily underwent amido-imidol tautomerism, yielding stable 1H-indazoles.

Synthesis of 4, 5-Dihydro-N(2)-Phenylindazole from Diversely Substituted Cyclic-β-Keto Esters and Its Structural Analysis

“…Characteristic reaction behavior of hydrazine as an effective nucleophile is exploiting for several reactions, especially for the synthesis of azole based compounds. In our previous reports hydrazine with cyclic-β-keto esters profited (1H)-Tetrahdydroindazole in high yield has been discussed [21][22]. In case of phenyl hydrazine, nucleophilicity is reduced due to the presence of aromatic ring.…”

Crystal structure of 3,6,6-trimethyl-4-oxo-1-(pyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazol-7-aminium chloride and its monohydrate

“…The broad application spectrum of tetrahydroindazoles has led to the development of synthetic methodologies. Thus, traditional approaches using a combination of either ,unsaturated ketones (Nakhai & Bergman, 2009) or dicarbonyl compounds (Murugavel et al, 2010), or tricarbonyl compounds (Kim et al, 2010;Scala et al, 2015) with hydrazines have been significantly updated and improved. In addition, the microwave-assisted synthesis of tetrahydroindazoles has been reported (Silva et al, 2006;Polo et al, 2016).…”

Synthesis, spectroscopic, topological, hirshfeld surface analysis, and anti-covid-19 molecular docking investigation of isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate

“…Heterocyclic compounds are planar rings of carbon atoms containing at least one heteroatom such as O, N, P and/or S in their structures 1 , 2 . They are of interest to scientists and researchers because of their applications in different areas of materials and pharmaceutical research 3 , 4 , 5 , 6 . Nitrogen heterocyclic compounds are important building blocks in the many bioactive natural products and commercial drugs.…”