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Synthesis 2008(3): 387-394  
DOI: 10.1055/s-2008-1032030
PAPER
© Georg Thieme Verlag Stuttgart · New York

Solution-Phase and Solid-Phase Synthesis of 1-Pyrazol-3-ylbenzimidazoles

Jaime Portillaa, Jairo Quiroga*a, Rodrigo Aboníaa, Braulio Insuastya, Manuel Noguerasb, Justo Cobob, Ernesto G. Mata*c
a Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A. A. 25360, Cali, Colombia
e-Mail: jaiquir@gmail.com;
b Departamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071 Jaén, Spain
c Instituto de Química Orgánica de Síntesis (CONICET - UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina
Fax: +54(341)4370477; e-Mail: mata@iquios.gov.ar;
Further Information

Publication History

Received 21 September 2007
Publication Date:
10 January 2008 (online)

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Abstract

The facile solution and solid-phase synthesis of 1-pyrazol-3-ylbenzimidazoles from 4-fluoro-3-nitrobenzoate derivatives and 5(3)-amino-3(5)-subtituted-1H-pyrazoles is reported. The key step is the unexpected nucleophilic aromatic displacement of the activated fluorine by the exocyclic amino group of the pyrazole ring leading to 4-pyrazolylamino-3-nitrobenzoate derivatives, which are easily converted into the corresponding 1-pyrazol-3-ylbenzimidazoles in very high isolated yield. These novel methodologies would be very useful for the generation of libraries of diverse 1-heteroaryl derivatives of benzimidazoles.

Key words

solid-phase synthesis - combinatorial chemistry - heterocycles - benzimidazoles - pyrazoles

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