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Synlett 2011(9): 1321-1323  
DOI: 10.1055/s-0030-1260552
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Copper(I)-Catalyzed Synthesis of Pyrazoles from Phenylhydrazones and Dialkyl Ethylenedicarboxylates in the Presence of Bases

Chaowei Ma, Yanmei Li, Ping Wen, Rulong Yan, Zhiyong Ren, Guosheng Huang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
Fax: +86(931)8912582; e-Mail: hgs@lzu.edu.cn;
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Publication History

Received 5 March 2011
Publication Date:
05 May 2011 (online)

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Abstract

An easy and efficient copper-catalyzed reaction for the synthesis of polysubstituted pyrazoles from phenylhydrazones and dialkyl ethylenedicarboxylates is described. This reaction can tolerate a range of functionalities, and the corresponding adducts can be obtained in moderate to good yields.

Key words

heterocycles - copper catalysis - hydrazones - dialkyl ethylenedicarboxylates - pyrazoles

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18

Typical Procedure for the Synthesis of Pyrazoles
An oven-dried reaction tube was charged with CuI (3.8 mg, 0.02 mmol), NaOAc (16.4 mg, 0.20 mmol), benzaldehyde phenylhydrazone (1a, 47.0mg, 0.24 mmol), and dimethyl acetylenedicarboxylate (2a, 28.4mg, 0.20 mmol). Then DME (2 mL) was added to the reaction system. The mixture was stirred at r.t. for 2 h. After removal of the solvent under reduced pressure, the crude product was purified by column chromatography on silica gel (EtOAc-PE, 1:8) to give 3aa (49.0 mg, 73%) as white solid (Table  [²] , entry 1); mp 152-154 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 7.75 (dd, J = 7.4, 1.8 Hz, 2 H), 7.54 (dd, J = 8.2, 1.4 Hz, 2 H), 7.50-7.40 (m, 6 H), 3.85 (s, 3 H), 3.82 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 163.37, 160.64, 151.98, 139.03, 136.82, 131.33, 129.16, 129.06, 128.87, 128.77, 128.16, 124.53, 114.13, 53.11, 52.12. IR (neat): 2952, 1733, 1499, 1447, 1266, 911, 732 cm-¹. HRMS: m/z calcd for C19H16N2O4 [M + H]+: 337.1183; found: 337.1175.