Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2018; 29(20): 2689-2692
DOI: 10.1055/s-0037-1610330
DOI: 10.1055/s-0037-1610330
letter
Efficient Copper-Catalyzed Synthesis of Substituted Pyrazoles at Room Temperature
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)
![](https://www.thieme-connect.de/media/synlett/201820/lookinside/thumbnails/st-2018-k0523-l_10-1055_s-0037-1610330-1.jpg)
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.
Key words
pyrazoles - condensation reaction - copper catalysis - arylhydrazines - sulfonyl hydrazidesSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610330.
- Supporting Information
-
References and Notes
- 1a McDonald E, Jones K, Brough PA, Drysdale MJ, Workman P. Curr. Top. Med. Chem. 2006; 6: 1193
- 1b Elguero J, Goya P, Jagerovic N, Silva AM. S. Targets Heterocycl. Syst. 2002; 6: 52
- 1c Terrett NK, Bell AS, Brown D, Ellis P. Bioorg. Med. Chem. Lett. 1996; 6: 1819
- 1d Elguero J. In Comprehensive Heterocyclic Chemistry II . Vol. 3, Chap. 3.01. Katritzky AR, Rees CW, Scriven EF. V. Pergamon; Oxford: 1996: 1
- 1e Keter FK, Darkwa J. BioMetals 2012; 25: 9
- 1f Havrylyuk D, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R. J. Med. Chem. 2012; 55: 8630
- 1g Fustero S, Sánchez-Roselló M, Barrio P, Simón-Fuentes A. Chem. Rev. 2011; 111: 6984
- 2a McGrath NA, Brichacek M, Njardarson JT. J. Chem. Educ. 2010; 87: 1348
- 2b Ilardi EA, Vitaku E, Njardarson JT. J. Chem. Educ. 2013; 90: 1403
- 2c Bekhit AA, Abdel-Aziem T. Bioorg. Med. Chem. 2004; 12: 1935
- 2d Selvam C, Jachak SM, Thilagavathi R, Chakraborti AK. Bioorg. Med. Chem. Lett. 2005; 15: 1793
- 3a Knorr L. Ber. Dtsch. Chem. Ges. 1883; 16: 2597
- 3b Wang Z.-X, Qin H.-L. Green Chem. 2004; 6: 90
- 3c Katritzky AR. Handbook of Heterocyclic Chemistry . Pergamon; Oxford: 1985: 416
- 3d Hayter MJ, Bray DJ, Clegg JK, Lindoy LF. Synth. Commun. 2006; 36: 707
- 3e Sanchez-Carmona MA, Contreras-Cruz DA, Miranda LD. Org. Biomol. Chem. 2011; 9: 6506
- 3f Vaddula BR, Varma RS, Leazer J. Tetrahedron Lett. 2013; 54: 1538
- 3g Zakerinasab B, Nasseri MA, Hassani H, Samieadel MM. Res. Chem. Intermed. 2016; 42: 3169
- 3h Polshettiwar V, Varma RS. Tetrahedron Lett. 2008; 49: 397
- 4 Shao N, Chen T, Zhang T, Zhu H, Zheng Q, Zou H. Tetrahedron 2014; 70: 795
- 5 Zhang H, Wei Q, Zhu G, Qu J, Wang B. Tetrahedron Lett. 2016; 57: 2633
- 6 Hu J, Chen S, Sun Y, Yang J, Rao Y. Org. Lett. 2012; 14: 5030
- 7a McLaughlin M, Marcantonio K, Chen C.-y, Davies IW. J. Org. Chem. 2008; 73: 4309
- 7b Dishington A, Feron JL, Gill K, Graham MA, Hollingsworth I, Pink JH, Roberts A, Simpson I, Tatton M. Org. Lett. 2014; 16: 6120
- 8a Vanjari R, Guntreddi T, Kumar S, Singh KN. Chem. Commun. 2015; 51: 366
- 8b Wen J.-J, Tang H.-T, Xiong K, Ding Z.-C, Zhan Z.-P. Org. Lett. 2014; 16: 5940
- 8c Yu X, Huang N, Feng X, Yamamoto Y, Bao M. Synthesis 2014; 46: 2422
- 9a Stoit AR, Lange JH. M, den Hartog AP, Ronken E, Tipker K, van Stuivenberg HH, Dijksman JA. R, Wals HC, Kruse CG. Chem. Pharm. Bull. 2002; 50: 1109
- 9b Chen X, She J, Shang Z.-C, Wu J, Zhang P. Synth. Commun. 2009; 39: 947
- 9c Gosselin F, O’Shea PD, Webster RA, Reamer RA, Tillyer RD, Grabowski EJ. J. Synlett 2006; 3267
- 9d Heller ST, Natarajan SR. Org. Lett. 2006; 8: 2675
- 9e Kumar SV, Yadav SK, Raghava B, Saraiah B, Ila H, Rangappa KS, Hazra A. J. Org. Chem. 2013; 78: 4960
- 9f Rosa FA, Machado P, Vargas PS, Bonacorso HG, Zanatta N, Martins MA. P. Synlett 2008; 1673
- 9g Ma C, Li Y, Wen P, Yan R, Ren Z, Huang G. Synlett 2011; 1321
- 9h Martín R, Rodríguez Rivero M, Buchwald SL. Angew. Chem. Int. Ed. 2006; 45: 7079
- 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.