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

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

References and Notes

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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.