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

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

References and Notes

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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: [phone];
e-mail: [e-mail]].