Abstract
An efficient and convenient solution-phase synthesis of a 1H-1,2,4-triazole library with potential agrochemical activity is reported employing microwave-assisted organic synthesis (MAOS) and continuous-flow microfluidic synthetic methods starting from commercially available 3,5-dibromo-1H-1,2,4-triazole (1). MAOS was used for the synthesis of 5-amino-3-bromo-1,2,4-triazole analogs 3 and for their 3-aryl derivatives 4 via Suzuki–Miyaura coupling with polymer-supported catalyst. A microfluidic hydrogenation reactor integrated into an automated parallel synthesis platform was built and utilized for the reductive dehalogenation reactions providing 5-aminotriazoles (5).
Graphical Abstract
References
New Report Global Biopesticides Market (2010–2015) Shifting Trends in Agrochemical Industry Published By MarketsandMarkets, http://www.marketsandmarkets.com
Shaber SH, Flynn KE, Fujimoto TT (1993) (Heterocyclylalkyl) ethyl-1,2,4-triazoles. EP0529973
Turan-Zitouni G, Kaplancikli ZA, Özdemir A, Chevallet P, Kandilci HB, Gümüşel B (2007) Studies on 1,2,4-triazole derivatives as potential anti-inflammatory agents. Arch Pharm 340(11): 586–590. doi:10.1002/ardp.200700134
Sung KS, Lee ARJ (1992) Synthesis of [(4,5-disubstituted-4H-1,2,4-triazol-3-yl)thio]alkanoic acids and their analogues as possible antiinflammatory agents. J Heterocyclic Chem 29: 1101–1109. doi:10.1002/jhet.5570290512
Prasad AR, Rao AN, Ramalingan T, Sattur PB (1988) Synthesis and biological activity 4-amino-3-aryloxyalkyl-5-mercapto-1,2,4-triazoles. Indian Drugs 25(7): 301–304
Wade PC, Vogt BR, Kissick TP, Simpkins JM, Palmer DM, Millonig RC (1982) 1-Acyltriazoles as antiinflammatory agents. J Med Chem 25: 331–333. doi:10.1021/jm00345a021
Maxwell JR, Wasdahl DA, Weltson DC, Stenberg VI (1984) Synthesis of 5-aryl-2H-tetrazoles, 5-aryl-2H-tetrazole-2-acetic acids, and [(4-phenyl-5-aryl-4H-1,2,4-triazol-3-yl)thio]acetic acids as possible superoxide scavengers and antiinflammatory agents. J Med Chem 27: 1565–1570. doi:10.1021/jm00378a007
Zarguil A, Boukhris S, El Efrit ML, Souizi A, Essassi EM (2008) Easy access to triazoles, triazolopyrimidines, benzimidazoles and imidazoles from imidates. Tetrahedron Lett 49: 5883–5886. doi:10.1016/j.tetlet.2008.07.134
Libnow S, Wille S, Christiansen A, Hein M, Reinke H, Köckerling M, Miethchen R (2006) Synthesis and reactivity of halogenated 1,2,4-triazole nucleoside analogues with high potential for chemical modifications. Synthesis 496–508. doi:10.1055/s-2006-926281
Zumbrunn A (1998) The first versatile synthesis of 1-alkyl-3-fluoro-1H-[1,2,4]triazoles. Synthesis 1357–1361. doi:10.1055/s-1998-6080
Glunz PW, Wurtz N, Cheng X (2006) Heterocyclic compounds as inhibitors of factor VIIA. WO2006062972A2
Jones R, Gödörházy L, Szalay D, Gerencsér J, Dormán G, Ürge L, Darvas F (2005) A novel method for high-throughput reduction of compounds through automated sequential injection into a continuous-flow microfluidic reactor. QSAR Comb Sci 24: 722–727. doi:10.1002/qsar.200540212
Clapham B, Wilson NS, Michmerhuizen MJ, Blanchard DP, Dingle DM, Nemcek TA, Pan JY, Sauer DR (2008) J Comb Chem 10: 88–93. doi:10.1021/cc700178a
Author information
Authors and Affiliations
Corresponding author
Additional information
This manuscript is dedicated to Professor Árpád Furka on the occasion of his 80th birthday.
Rights and permissions
About this article
Cite this article
Szommer, T., Lukács, A., Kovács, J. et al. Parallel synthesis of 1,2,4-triazole derivatives using microwave and continuous-flow techniques. Mol Divers 16, 81–90 (2012). https://doi.org/10.1007/s11030-012-9357-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11030-012-9357-2