Base-Promoted Ecofriendly Synthesis of Trisubstituted Pyrazoles from α,β-Alkynyl N-Tosylhydrazones under Metal- and Solvent-Free Conditions

Abstract

A simple and green method is described for the synthesis of trisubstituted pyrazoles from α,β-alkynyl N-tosylhydrazones under metal- and solvent-free conditions. Notably, only diisopropylamine is required as a promoter, and the reaction can be easily performed at room temperature and on a gram scale.

Keywords

hydrazones - green chemistry - pyrazoles - cyclizations

• References and Notes


For a selected monograph and reviews, see:
• 1a Yet L. Prog. Heterocycl. Chem. 2009; 20: 190
• 1b Gulevich AV, Dudnik AS, Chernyak N, Gevorgyan V. Chem. Rev. 2013; 113: 3084
• 1c Fustero S, Sánchez-Roselló M, Barrio P, Simón-Fuentes A. Chem. Rev. 2011; 111: 6984
• 1d Dadiboyena S, Nefzi A. Eur. J. Med. Chem. 2011; 46: 5258
• 2 Ouyang G, Cai X.-J, Chen Z, Song B.-A, Bhadury PS, Yang S, Jin L.-H, Xue W, Hu D.-Y, Zeng S. J. Agric. Food Chem. 2008; 56: 10160
• 3 Bebernitz GR, Argentieri G, Battle B, Brennan C, Balkan B, Burkey BF, Eckhardt M, Gao J, Kapa P, Strohschein RJ, Schuster HF, Wilson M, Xu DD. J. Med. Chem. 2001; 44: 2601
• 4a Sridhar R, Perumal PT, Etti S, Shanmugam G, Ponnuswamy MN, Prabavathy VR, Mathivanan N. Bioorg. Med. Chem. Lett. 2004; 14: 6035
• 4b Liu J.-J, Sun J, Fang Y.-B, Yang Y.-A, Jiao R.-H, Zhu H.-L. Org. Biomol. Chem. 2014; 12: 998
• 5 Chang C.-P, Wu C.-H, Song J.-S, Chou M.-C, Wong Y.-C, Lin Y, Yeh T.-K, Sadani AA, Ou M.-H, Chen K.-H, Chen P.-H, Kuo P.-C, Tseng C.-T, Chang K.-H, Tseng S.-L, Chao Y.-S, Hung M.-S, Shia K.-S. J. Med. Chem. 2013; 56: 9920
• 6 Habeeb AG, Rao PN. P, Knaus EE. J. Med. Chem. 2001; 44: 3039
• 7 Abdel-Magid AF. ACS Med. Chem. Lett. 2014; 5: 730
• 8a DeWald HA, Lobbestael S, Poschel BP. H. J. Med. Chem. 1981; 24: 982
• 8b Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S, Graneto MJ, Lee LF, Malecha JW, Miyashiro JM, Rogers RS, Rogier DJ, Yu SS, Anderson GD, Burton EG, Cogburn JN, Gregory SA, Koboldt CM, Perkins WE, Seibert K, Veenhuizen AW, Zhang YY, Isakson PC. J. Med. Chem. 1997; 40: 1347
• 8c Barth F, Rinaldi-Carmona M. Curr. Med. Chem. 1999; 6: 745
• 8d Dale DJ, Dunn PJ, Golightly C, Hughes ML, Levett PC, Pearce AK, Searle PM, Ward G, Wood AS. Org. Process Res. Dev. 2000; 4: 17

For selected monographs and reviews, see:
• 9a Yet L In Comprehensive Heterocyclic Chemistry III . Vol. 4. Katritzky AR, Ramsden CA, Scriven EF. V. R, Taylor JK. Chap. 4.01 Elsevier; Amsterdam: 2008: 1
• 9b Stanovnik B, Svete J In Science of Synthesis . Neier R. Thieme; Stuttgart: 2002
• 9c Kumari S, Paliwal S, Chauhan R. Synth. Commun. 2014; 44: 1521
• 9d Janin YL. Chem. Rev. 2012; 112: 3924
• 9e Stanovnik B, Svete J. Chem. Rev. 2004; 104: 2433
• 10a Padwa A. 1,3-Dipolar Cycloaddition Chemistry . Vol. 1. Wiley; New York: 1984
• 10b Padwa A, Pearson WH. Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Wiley; New York: 2002
• 10c Zhang F.-G, Wei Y, Yi Y.-P, Nie J, Ma J.-A. Org. Lett. 2014; 16: 3122
• 10d Merchant RR, Allwood DM, Blakemore DC, Ley SV. J. Org. Chem. 2014; 79: 8800
• 11a Zhao Y, Bacher A, Illarionov B, Fischer M, Georg G, Ye Q.-Z, Fanwick PE, Franzblau SG, Wan B, Cushman M. J. Org. Chem. 2009; 74: 5297
• 11b Gerstenberger BS, Rauckhorst MR, Starr JT. Org. Lett. 2009; 11: 2097
• 12a Anderson KW, Tundel RE, Ikawa T, Altman RA, Buchwald SL. Angew. Chem. Int. Ed. 2006; 45: 6523
• 12b Correa A, Bolm C. Angew. Chem. Int. Ed. 2007; 46: 8862
• 12c Zhu L, Guo P, Li G, Lan J, Xie R, You J. J. Org. Chem. 2007; 72: 8535
• 12d Deng X, Mani NS. Org. Lett. 2008; 10: 1307
• 12e Guillou S, Nesmes O, Ermolenko MS, Janin YL. Tetrahedron 2009; 65: 3529
• 12f Delaunay T, Genix P, Es-Sayed M, Vors J.-P, Monteiro N, Balme G. Org. Lett. 2010; 12: 3328
• 13a Xu S.-X, Hao L, Wang T, Ding Z.-C, Zhan Z.-P. Org. Biomol. Chem. 2013; 11: 294
• 13b Hao L, Hong J.-L, Zhu J.-J, Zhan Z.-P. Chem. Eur. J. 2013; 19: 5715

For recent examples, see:
• 14a Ji G, Wang X, Zhang S, Xu Y, Ye Y, Li M, Zhang Y, Wang J. Chem. Commun. 2014; 50: 4361
• 14b Kusakabe T, Sagae H, Kato K. Org. Biomol. Chem. 2013; 11: 4943
• 14c Suzuki Y, Naoe S, Oishi S, Fujii N, Ohno H. Org. Lett. 2012; 14: 326
• 14d Qian J, Liu Y, Zhu J, Jiang B, Xu Z. Org. Lett. 2011; 13: 4220
• 14e Zora M, Kivrak A. J. Org. Chem. 2011; 76: 9379
• 14f Zora M, Kivrak A, Yazici C. J. Org. Chem. 2011; 76: 6726
• 14g Willy B, Müller TJ. J. Org. Lett. 2011; 13: 2082
• 14h Waldo JP, Mehta S, Larock RC. J. Org. Chem. 2008; 73: 6666
• 15a Marković V, Joksović MD. Green Chem. 2015; 17: 842
• 15b Srivastava M, Rai P, Singh J, Singh J. New J. Chem. 2014; 38: 302
• 15c Srivastava M, Rai P, Singh J, Singh J. RSC Adv. 2013; 3: 16994
• 15d Kumari K, Raghuvanshi DS, Jouikov V, Singh KN. Tetrahedron Lett. 2012; 53: 1130
• 16 Chen S, Yuan F, Zhao H, Li B. RSC Adv. 2013; 3: 12616
• 17 Liu W, Zhao H, Li B, Chen S. Synlett 2015; 26: 2170
• 18 Pyrazoles 2; General Procedure i-Pr₂NH (0.6 mmol) and the appropriate N-tosylhydrazone 1 (0.3 mmol) were thoroughly ground with a pestle and mortar for 30 min. When the reaction was complete, the mixture was purified by crystallization from CH₂Cl₂ or by column chromatography (silica gel, EtOAc–PE) to give the pure pyrazole product 2. 3,5-Diphenyl-1-tosyl-1H-pyrazole (2a) White solid; yield: 103 mg (92%; gram scale: 81%); mp 122–124 °C. IR (KBr): 3029, 2921, 2855, 1594, 1558, 1459, 1382, 1195, 1177, 761, 660, 598 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 2.35 (s, 3 H), 6.60 (s, 1 H), 7.19 (d, J = 8.0 Hz, 2 H), 7.35–7.45 (m, 8 H), 7.62 (d, J = 8.0 Hz, 2 H), 7.84 (d, J = 7.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 21.69, 109.54, 126.48, 127.84, 128.04, 128.72, 129.33, 129.49, 129.62, 129.67, 130.02, 131.37, 134.88, 145.35, 149.48, 155.21. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₉N₂O₂S: 375.1167; found: 375.1161.