N,N-Bond-Forming Heterocyclization:  Synthesis of 3-Alkoxy-2H-indazoles

Abstract

A one-step heterocyclization of o-nitrobenzylamines to 3-alkoxy-2H-indazoles is reported. The electronic nature of the nitrophenyl group, the steric and electronic nature of the R1-functionalized benzylic amine, and the nature of the alcoholic solvent affect the efficiency of this heterocyclization reaction (approximately 40-90%).

Inhibition of myeloperoxidase: Evaluation of 2H-indazoles and 1H-indazolones

“…The 3-alkoxy-2 H -indazoles employed in this study were prepared by the versatile Davis-Beirut reaction (DBR) 23–29 on 2-nitrobenzylamine 3 , in turn prepared by one of two complimentary methods: (i) commercially available 2-nitrobenzyl bromide ( 1 ) was used to N -alkylate the requisite amine to form intermediate 3 (Scheme 1/Method A) or (ii) 3 was prepared by reductive amination of the requisite 2-nitrobenzaldehyde (Scheme 1/Method B). Regardless of the route to 3 , this 2-nitrobenzylamine intermediate need not be isolated.…”

Synthesis of indazole motifs and their medicinal importance: An overview

“…KOH (Scheme-55) [69]. All nitro substituted reactant gives very effective final yields are reported bellow.…”

A new effective route for the synthesis of substituted 2h-indazoles

“…It is important to underline that at present a wide range of precursors has been used to synthesize the 2H-indazole ring, in practice including all strategic routes for its synthesis. For example, 2H-indazoles have been synthesized from 2-azidobenzylideneamines [17] or 2-azidobenzoylamines [18,19], oxidative cyclization from N-acylhydrazones of 2-aminoacylbenzenes [20,21], reaction of carbenes with azobenzene [22,23], rearrangement of ortho-substituted azobenzenes [24,25], and reductive heterocyclization of ortho-nitrobenzylideneamines [26][27][28], and heterocyclization of ortho-nitrobenzylamines [29][30][31][32][33]. A variant of the formation of the 2H-indazole system from compounds containing the pyrazole unit have been described.…”

“…For example, oxidation of 4,5-tetramethylenepyrazoles with dichlorodicyanobenzoquinone gave substituted 2H-indazoles in high yield [34]. However, despite the abundance of variants for the construction of the 2H-indazole ring, the variation of substituents is practically limited to those in positions 2 and 3, and only in the papers [30,31,33] were syntheses of 2H-indazoles containing substituents in the annelated benzene ring reported. …”