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Synlett 2011(15): 2214-2222  
DOI: 10.1055/s-0030-1261202
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Multicomponent Synthesis of Fully Substituted Pyrazoles and Bispyrazoles Catalyzed by Zinc Triflate

Shirin Safaei, Iraj Mohammadpoor-Baltork*, Ahmad Reza Khosropour*, Majid Moghadam, Shahram Tangestaninejad, Valiollah Mirkhani
Catalysis Division, Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran
Fax: +98(311)6689732; e-Mail: imbaltork@sci.ui.ac.ir; e-Mail: arkhosropour@sci.ui.ac.ir;
Further Information

Publication History

Received 20 April 2011
Publication Date:
30 August 2011 (online)

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Abstract

A variety of fully substituted pyrazoles were easily prepared through a three-component condensation of aldehydes, arylhydrazines, and ethyl acetoacetate in the presence of catalytic amounts of zinc triflate [Zn(OTf)2] under solvent-free conditions. Selective synthesis of symmetrical and unsymmetrical bispyrazoles from dialdehydes in high yields can be considered as a notable advantage of this method.

Key words

pyrazoles - aldehydes - arylhydrazines - zinc triflate - solvent-free

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General Procedure for the Synthesis of Fully Substituted Pyrazoles A mixture of aldehyde 1 (1 mmol) and arylhydrazine 2 (1 mmol) was stirred for 20 min, then ethyl acetoacetate 3 (1.5 mmol) and Zn(OTf)2 (0.02 mmol) were added, and the mixture was stirred at 120 ˚C for the appropriate time according to Table  [²] . The progress of the reaction was monitored by TLC (eluent: n-hexane-EtOAc, 10:1). After completion of the reaction, the mixture was cooled to r.t., and the crude product was purified by chromatography on silica gel (eluent: n-hexane-EtOAc, 10:1) or by recrystallization from EtOH to afford the pure product.

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General Procedure for the Synthesis of Fully Substituted Bispyrazoles A mixture of dialdehyde 5 (1 mmol) and arylhydrazine 2 (2 mmol) was stirred for 20 min (for unsymmetrical bispyrazoles, a mixture of dialdehyde 5 (1 mmol) and arylhydrazine 2 (1 mmol) was stirred for 20 min, then arylhydrazine 6 (1 mmol) was added and stirred for further 20 min). Ethyl acetoacetate 3 (4 mmol) and Zn(OTf)2 (0.04 mmol) were added, and the mixture was heated at 120 ˚C for the appropriate time (Table  [³] ). The progress of the reaction was monitored by TLC (eluent: n-hexane-EtOAc, 10:1). After completion of the reaction, the mixture was cooled to r.t., and the crude product was purified by chromatography on silica gel (eluent: n-hexane-EtOAc, 10:1) or by recrystallization from EtOH to give the pure product.

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CCDC 817131 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033;
e-mail: deposit@ccdc.cam.ac.uk].