An Efficient One-Pot Synthesis of 3,5-Diaryl-4-bromopyrazoles by 1,3-Dipolar Cycloaddition of In Situ Generated Diazo Compounds and 1-Bromoalk-1-ynes

Abstract

A simple, highly efficient, one-pot synthesis of 3,5-di­aryl-4-bromopyrazoles via 1,3-dipolar cycloaddition of diazo compounds and alkynyl bromides has been developed. The diazo compounds and alkynyl bromides were generated in situ from tosylhydrazones and gem-dibromoalkenes, respectively. When ketone-derived hydrazones were used, 3,5-diaryl-4-bromo-3H-pyrazoles were obtained and the isomerization products 3,5-diaryl-4-bromo-1H-pyrazoles were formed when using aldehyde-derived hydrazones. The reaction system exhibited high regioselectivity and good functional group tolerance. Both electron-rich and electron-deficient­ substituents on the aromatic ring of the hydrazones or the gem-dibromoalkenes gave desired products in moderate to good yields (67–86%).

Key words

cycloaddition - diazo compounds - hydrazones - pyrazoles - gem-dibromoalkenes

• References

• 1a Elguero J. In Comprehensive Heterocyclic Chemistry . Vol. 5. Katritzky AR. Pergamon; Oxford: 1984: 277
• 1b Elguero J. Pyrazoles, In Comprehensive Heterocyclic Chemistry II . Vol. 3. Katritzky AR, Rees CW, Scriven EF. V. Pergamon; Oxford: 1996
• 1c Elguero J, Goya P, Jagerovic N, Silva AM. S. Pyrazoles as Drugs: Facts and Fantasies, In Targets in Heterocyclic Systems . Vol. 6. Attanasi OA, Spinelli D. Royal Society of Chemistry; Cambridge UK: 2002: 52
• 2a Candeias NR, Branco LC, Gois PM. P, Afonso CA. M, Trindade AF. Chem. Rev. 2009; 109: 2703
• 2b Fustero S, Sánchez-Roselló M, Barrio P, Simón-Fuentes A. Chem. Rev. 2011; 111: 6984
• 3a Goikhman R, Jacques TL, Sames D. J. Am. Chem. Soc. 2009; 131: 3042
• 3b Mateos C, Mendiola J, Carpintero M, Mínguez JM. Org. Lett. 2010; 12: 4924
• 3c Janin YL. Chem. Rev. 2012; 122: 3924
• 4a Kost AN, Grandberg II. Adv. Heterocycl. Chem. 1966; 6: 347
• 4b Katritzky AR, Wang MY, Zhang SM, Voronkov MV. J. Org. Chem. 2001; 66: 6787
• 4c Heller ST, Natarajan SR. Org. Lett. 2006; 8: 2675
• 4d Frizzo CP, Moreira DN, Guarda EA, Fiss GF, Marzari MR. B, Zanatta N, Bonacorso HG, Martins MA. P. Catal. Commun. 2009; 10: 1153
• 5a Padwa A. 1,3-Dipolar Cycloaddition Chemistry . Vol. I. John Wiley & Sons; New York: 1984
• 5b Vuluga D, Legros J, Crousse B, Bonnet-Delpon D. Green Chem. 2009; 11: 156
• 6a Ye T, McKervey MA. Chem. Rev. 1994; 94: 1091
• 6b Doyle MP, McKervey MA, Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds . Wiley-Interscience; New York: 1998
• 7 Aggarwal VK, Vicente JD, Bonnert RV. J. Org. Chem. 2003; 68: 5381
• 8 Wu LL, Ge YC, He T, Zhang L, Fu XL, Fu HY, Chen H, Li RX. Synthesis 2012; 44: 1577
• 9a Li P, Zhao JJ, Wu CR, Larock RC, Shi F. Org. Lett. 2011; 13: 3340
• 9b Ma CW, Li YM, Wen P, Yan RL, Ren ZY, Huang GS. Synlett 2011; 1321
• 9c Li P, Wu CR, Zhao JJ, Rogness DC, Shi F. J. Org. Chem. 2012; 77: 3149
• 9d Fulton JR, Aggarwal VK, Vicente JD. Eur. J. Org. Chem. 2005; 1479
• 9e Shao ZH, Zhang HB. Chem. Soc. Rev. 2012; 41: 560
• 10 Atherton JH, Field R. J. Chem. Soc. 1968; 1507
• 11a Hanamoto T, Koga Y, Kido E, Kawanami T, Furuno H, Inanaga J. Chem. Commun. 2005; 2041
• 11b Hanamoto T, Suetake T, Koga Y, Kawanami T, Furuno H, Inanaga J. Tetrahedron 2007; 63: 5062
• 11c Hanamoto T, Iwamoto Y, Yamada K, Anno R. J. Fluorine Chem. 2007; 128: 1126
• 12 Makhsumov AG, Atakhodzhaeva MA, Talipova MA, Dzhuraev AD. Pharm. Chem. J. 1988; 22: 306
• 13a Berciano BP, Lebrequier S, Besselièvre F, Piguel S. Org. Lett. 2010; 12: 4038
• 13b Reddy GC, Balasubramanyam P, Salvanna N, Das B. Eur. J. Org. Chem. 2012; 471
• 13c Ackermann L, Kornhaass C, Zhu YJ. Org. Lett. 2012; 14: 1824
• 14 Zhao ZG, Wang ZX. Synth. Commun. 2007; 37: 137
• 15a Sibi MP, Itoh K. J. Am. Chem. Soc. 2007; 129: 8064
• 15b Zueva EM, Petrova MM, Herchel R, Trávníček Z, Raptis RG, Mathivathananc L, McGrady JE. Dalton Trans. 2009; 5924
• 16 Garg HG. J. Org. Chem. 1961; 26: 948
• 17a Pincock JA, Morchat R, Arnold DR. J. Am. Chem. Soc. 1973; 95: 7536
• 17b Arnold DR, Humphreys RW, Leigh WJ, Palmer GE. J. Am. Chem. Soc. 1976; 98: 6225
• 17c Pincock JA, Mathur NC. J. Org. Chem. 1982; 47: 3699
• 17d Jefferson EA, Warkentin J. J. Org. Chem. 1994; 59: 455
• 17e Quiclet-Sire B, Zard SZ. Chem. Commun. 2006; 1831
• 17f Ahmed SA, Al-Raqa SY. Monatsh. Chem. 2010; 141: 357
• 17g Xing J, Wang XR, Yan CX, Cheng Y. J. Org. Chem. 2011; 76: 4746
• 17h Wang XR, Xing J, Yan CX, Cheng Y. Org. Biomol. Chem. 2012; 10: 970
• 18a Elguero J, Marzin C, Roberts JD. J. Org. Chem. 1974; 39: 357
• 18b Chenon MT, Coupry C, Grant DM, Pugmire RJ. J. Org. Chem. 1977; 42: 659
• 18c Begtrup M, Boyer G, Cabildo P, Cativiela C, Claramunt RM, Elguero J, García JL, Toiron C, Vedsø P. Magn. Reson. Chem. 1993; 31: 107
• 18d de Paz JL. G, Elguero J, Foces-Foces C, Llamas-Saiz A, Aguilar-Parrilla F, Klein O, Limbach H.-H. J. Chem. Soc., Perkin Trans. 2 1997; 101
• 18e Ramos M, Alkorta I, Eiguero J. Tetrahedron 1997; 53: 1403
• 18f Jarończyk M, Dobrowolski JC, Mazurek AP. J. Mol. Struct.: THEOCHEM 2004; 673: 17
• 19a Zhou L, Ye F, Ma JC, Zhang Y, Wang JB. Angew. Chem. Int. Ed. 2011; 50: 3510
• 19b Libermann D, Moyeux M, Rouaix A, Maillard J, Hengl L, Himbert J. Bull. Soc. Chim. Fr. 1953; 957
• 20a Rao ML. N, Jadhav DN, Dasgupta P. Org. Lett. 2010; 12: 2048
• 20b Ramirez F, Desai NB, McKelvie N. J. Am. Chem. Soc. 1962; 84: 1745