Regioselective Synthesis of 1-Alkyl- or 1-Aryl-1H-indazoles via Copper-Catalyzed Cyclizations of 2-Haloarylcarbonylic Compounds

Abstract

[reaction: see text] A general method for the one-step regioselective synthesis of 1-alkyl- or 1-aryl-1H-indazoles from ortho-halogenated alkanoylphenones, benzophenones, and arylcarboxylic acids, via copper-catalyzed amination, was developed by using 0.2% mol of CuO in the presence of K(2)CO(3). The reaction involves amination followed by intramolecular dehydration. Different functionalized alkyl aryl ketones, diaryl ketones, and benzoic acid derivatives were efficiently coupled with several hydrazines. Ligands commonly employed as catalysts for intermolecular amination were shown to be ineffective for this cyclization.

Rapid and halide compatible synthesis of 2-N-substituted indazolone derivatives via photochemical cyclization in aqueous media

“…Due to their versatility in pharmaceutical applications, many synthetic approaches have been developed for the construction of indazolone skeletons (Scheme 2), including CuO-mediated coupling of 2-haloarylcarboxylic acids with methylhydrazine, 10 cyclization of N-aryl-o-nitrobenzamides through Ti(VI) reagent or Zn(II) reagent, 11 Cu(I)-mediated intramolecular C-N bond formation or a base-mediated intramolecular SNAr reaction of 2-halobenzohydrazides, 12 Cu(I)-catalyzed oxidative C-N crosscoupling and dehydrogenative N-N formation sequence, 13 Rhcatalyzed C-H activation/C-N bond formation and Cucatalyzed N-N bond formation between azides and arylimidates, 14 Friedel-Cras cyclization of N-isocyanates using Masked N-isocyanate precursors, 15 PIFA-mediated intramolecular oxidative N-N bond formation by trapping of Nacylnitrenium intermediates, 16 and recently reported reaction of o-nitrobenzyl alcohol with primary amines in basic conditions. 17 These approaches are complementary providing avenue to access various substitution patterns, 18 however most methods rely on the requirements for transition-metal catalysts.…”

Two‐Step Synthesis of Blue Luminescent (Pyrrol‐3‐yl)‐1H‐(aza)indazoles Based on a Three‐Component Coupling–Cyclocondensation Sequence

“…Many syntheses of the indazole core are based upon cyclocondensation reaction of ortho ‐halo substituted aromatic aldehydes and ketones with corresponding hydrazine derivatives 1b. As variations of this general approach, a Cu II oxide catalyzed process was recently disclosed 14. With hydrazones as presumed and actual intermediates a Pd‐catalyzed version has been proposed, which only proceeds in modest yield 15.…”

Regioselective Synthesis of 1‐Substituted Indazole‐3‐carboxylic Acids

“…In general, the regioselective preparation of 1‐substituted indazoles is difficult to achieve, as 2‐substituted product will always form as a side product. To achieve regioselectivity, Vina et al reported a general Ullmann method in the presence of 0.2 mol% of CuO and K 2 CO 3 in good yields (16–83%). Huat et al reported selective 1‐functionalization with Cs 2 CO 3 (3 equiv) and DMF with 50–95% yields.…”