Synlett 2018; 29(20): 2689-2692
DOI: 10.1055/s-0037-1610330
letter
© Georg Thieme Verlag Stuttgart · New York

Efficient Copper-Catalyzed Synthesis of Substituted Pyrazoles at Room Temperature

Haifeng Wang*
School of Chemistry & Chemical Engineering, Zhoukou Normal University, Zhoukou, 466001, Henan, P. R. of China   Email: [email protected]
,
Xiangli Sun
,
Shuangling Zhang
,
Guanglu Liu
,
Chunjie Wang
,
Lili Zhu
,
Hui Zhang
› Author Affiliations
The work is supported by a high-level personal fund of Zhoukou Normal University (No. ZKNUC2017040).
Further Information

Publication History

Received: 15.09.2018

Accepted after revision: 22 October 2018

Publication Date:
15 November 2018 (online)


Abstract

An efficient method for the synthesis of pyrazoles through a copper-catalyzed condensation reaction has been developed. The new catalytic system not only maintained a broad substrate scope but was also active under acid-free reaction conditions, overcoming the conventional requirement for an acid-catalyzed system. Furthermore, the copper catalyst enabled this reaction to be performed at room temperature and in a short reaction time.

Supporting Information

 
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  • 10 3,5-Dimethyl-1-phenyl-1H-pyrazole (3a); Typical ProcedureCu(NO3)2·3 H2O (10 mol%) was added to a stirred solution of PhNHNH2 (1a; 0.5 mmol) and pentane-2,4-dione (2; 0.6 mmol) in CH3CN (2 mL) at r.t., and the resulting solution was stirred at r.t. for 1 h. When the reaction was complete, the mixture was concentrated to remove MeCN, and the residue was dissolved in CH2Cl2 (30 mL). The organic layer was washed with H2O (3 × 10 mL), dried (Na2SO4), filtered, concentrated, and purified by column chromatography [silica gel, PE–EtOAc (20:1)] to give a colorless oil; yield: 75 mg (87%). 1H NMR (400 MHz, CDCl3): δ = 7.46–7.40 (m, 4 H), 7.36–7.32 (m, 1 H), 6.01 (s, 1 H), 2.32 (s, 3 H), 2.31 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 148.94, 139.99, 139.35, 128.98, 127.21, 124.75, 106.94, 13.53, 12.37. HRMS (ESI): m/z [M + H]+ calcd for C11H13N2: 173.1073; found: 173.1074.
  • 11 3,5-Dimethyl-1-tosyl-1H-pyrazole (5a); Typical ProcedurePentane-2,4-dione (2; 0.6 mmol) and Cu(NO3)2·3H2O (10 mol%) were added to a round-bottomed flask containing a solution of TsNHNH2 (4a, 0.5 mmol) in CH3CN (2 mL), and the mixture was stirred for 15 min. The mixture was then concentrated to remove MeCN, and the residue was dissolved in CH2Cl2 (30 mL). The organic layer was washed with H2O (3 × 10 mL), dried (Na2SO4), filtered, concentrated, and purified by column chromatography [silica gel, PE–EtOAc (20:1)] to give a white solid; yield 101 mg (81%); mp 97–98 °C. 1H NMR (400 MHz, CDCl3): δ = 7.83 (d, J = 8.3 Hz, 2 H), 7.31 (d, J = 8.1 Hz, 2 H), 5.90 (s, 1 H), 2.49 (s, 3 H), 2.41 (s, 3 H), 2.20 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 153.46, 145.22, 144.15, 135.48, 129.96, 127.63, 110.81, 21.71, 13.90, 13.16. HRMS (ESI): m/z [M + H]+ calcd for C12H15N2O2S: 251.0849; found: 251.0846.