Recent synthetic approaches to 1 H - and 2 H -indazoles (microreview)
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Recent synthetic approaches to 1H- and 2H-indazoles (microreview) Gaurav S. Rai1, Jayesh J. Maru1* 1
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad-380009, Navrangpura, India; е-mail: [email protected]
Published in Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(8), 973–975
Submitted April 2, 2020 Accepted April 29, 2020
The work summarizes latest strategies for the synthesis of 1H- and 2H-indazoles published during the last five years. The strategies include transition metal catalyzed reactions, reductive cyclization reactions, and synthesis of 2H-indazoles via consecutive formation of C–N and N–N bonds without catalyst and solvent from 2-azidobenzaldehydes and amines. This review article gives a brief outline of optimized synthetic schemes with relevant examples. Introduction Indazole-containing heterocyclic compounds have a wide variety of medicinal applications as antihypertensive, anticancer, antidepressant, anti-inflammatory, and antibacterial agents.1 Several recently marketed drugs contain indazole structural motif. Indazoles can also be employed as selective inhibitors of phosphoinositide 3-kinase δ for the treatment of respiratory disease.2 Thus, much effort has been spent in recent years to develop synthetic approaches to indazoles, including reactions under catalyst- and solventfree conditions,3 Cu2O-mediated cyclization of o-haloarylN-tosylhydrazones,4 Ag-catalyzed nitration–annulation with tert-butyl nitrite,5 iodine-mediated intramolecular aryl and sp3 C–H amination,6 and metal-free reaction of aryl-
hydrazones with montmorillonite K-10 under O2 atmosphere.7 Literature presents several classic noncatalytic pathways toward the synthesis of indazoles such as condensation of o-fluorobenzaldehydes or their O-methyloximes with hydrazine,8 selective activation of the oxime group in o-aminobenzoximes in the presence of methanesulfonyl chloride and triethylamine,9 and intramolecular electrophilic amination of 2-aminophenyl ketoximes.10 However, lower yields as well as undesirable byproducts are the major concerns for the metal-free synthetic approaches. Metal-catalyzed synthesis generally produces good to excellent yields, with minimal formation of byproducts.
Transition metal catalyzed approach A Cu(OAc)2-catalyzed facile synthesis of 1H-indazoles by N–N bond formation employing oxygen as the terminal oxidant has been described.11 First, 2-(methylamino)benzonitrile 1 with an organometallic reagent formed N–H ketimine species 2 followed by Cu(OAc)2-catalyzed reaction to form N–N bond in DMSO under O2 atmosphere, to afford a wide variety of 1H-indazoles 3 in good to excellent yields. Jayesh J. Maru is assistant professor at the Department of Chemistry, School of Sciences, Gujarat University (Ahmedabad, India). He defended his PhD thesis, conducted under the guidance of associate professor G. R. Patel, in 2015 at Hemchandracharya, North Gujarat University. His scientific interests include chemistry of heterocyclic compounds, novel strategies for the synthesis of
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