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

Abstract

A two-stage synthesis of 2H-indazoles has been established, based on consecutive reactions of reduction of 2-alkyl-, 2-cyclopropyl-, and 2-arylcarbonylazobenzenes to phenylazo-substituted benzyl alcohols and intramolecular heterocyclization of the reduction products under the influence of organic acids.In recent years there has been a considerably strengthened interest in the synthesis and study of the medicobiological properties of derivatives of 2H-indazoles, resulting from the observation in a series of compounds which are seldom encountered in nature, a class of heterocycles with a wide range of biological activity: antiangiogenic [1], anticarcinogenic and anti-inflammatory [2,3], antimicrobial [4], antifungal [5,6], cytotoxic [7], and antihelminthic [8]. In addition compounds of this class show potential as inhibitors of NO-synthetases [9, 10], protein kinases [11,12], tubulin [13], modulators of X-receptors of the liver [14], and they also show properties of male contraceptives [15,16].The discovery of the biological activity of the 2H-indazoles caused the real problem of the synthesis of new derivatives of this class of heterocycles. 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.

Synthesis of quinolin-2-ones by an intramolecular Knoevenagel condensation and by tandem Michael–Knoevenagel heterocyclization

“…Yield 84%; mp 90-91 o C (EtOH). 1 1-(7-Amino-2,3-dihydro-1,4-benzodioxin-6-yl)butan-1-one (6) was synthesized by the reduction of 1-(7-nitro-2,3-dihydro-1,4-benzodioxin-6-yl)butan-1-one by the procedure of [28]. Yield 77%; mp 65-66 o C (EtOH).…”

“…Most of the ortho-acylanilines 1-5, 7-14, 17-19 used were synthesized as described in [23][24][25][26][27][28], but 6-amino-7-butyroyl-1,4-benzodioxane (6), 6-amino-7-(2-iodobenzoyl)-1,4-benzodioxane (15), and 2-amino-4,5-dimethoxyacetophenone (16), were obtained by the reduction of the corresponding nitro compounds (see EXPERIMENTAL). All the R-acylaminobenzenes 20-49 had not been obtained previously, their yields and physicochemical characteristics are given in Tables 1-3.…”