Syntheses of 1-Aryl-5-nitro-1H-indazoles and a General One-Pot Route to 1-Aryl-1H-indazoles

Joel K Annor-Gyamfi; Krishna Kumar Gnanasekaran; Richard A Bunce

doi:10.3390/molecules23030674

Syntheses of 1-Aryl-5-nitro-1H-indazoles and a General One-Pot Route to 1-Aryl-1H-indazoles

Molecules. 2018 Mar 16;23(3):674. doi: 10.3390/molecules23030674.

Authors

Joel K Annor-Gyamfi¹, Krishna Kumar Gnanasekaran², Richard A Bunce³

Affiliations

¹ Department of Chemistry, Oklahoma State University, Stillwater, OK 74078-3071, USA. jannorg@okstate.edu.
² Department of Chemistry, Oklahoma State University, Stillwater, OK 74078-3071, USA. krishna.gnanasekaran@okstate.edu.
³ Department of Chemistry, Oklahoma State University, Stillwater, OK 74078-3071, USA. rab@okstate.edu.

Abstract

An efficient route to substituted 1-aryl-1H-indazoles has been developed and optimized. The method involved the preparation of arylhydrazones from acetophenone or benzaldehyde substituted by fluorine at C2 and nitro at C5, followed by deprotonation and nucleophilic aromatic substitution (S_NAr) ring closure in 45-90%. Modification of this procedure to a one-pot domino process was successful in the acetophenone series (73-96%), while the benzaldehyde series (63-73%) required a step-wise addition of reagents. A general one-pot protocol for 1-aryl-1H-indazole formation without the limiting substitution patterns required for the S_NAr cyclization has also been achieved in 62-78% yields. A selection of 1-aryl-1H-indazoles was prepared in high yield by a procedure that requires only a single laboratory operation.

Keywords: 1-aryl-1H-indazole; 1-aryl-5-nitro-1H-indazole; SNAr reaction; Ullmann reaction; arylhydrazone.

MeSH terms

Acetophenones / chemistry
Benzaldehydes / chemistry
Catalysis
Cyclization
Indazoles / chemical synthesis*
Indazoles / chemistry*
Molecular Structure

Substances

Acetophenones
Benzaldehydes
Indazoles
acetophenone
benzaldehyde