Synlett, Table of Contents Synlett 2018; 29(20): 2685-2688DOI: 10.1055/s-0037-1610323 letter © Georg Thieme Verlag Stuttgart · New York Synthesis of 1,4-Disubstituted 1H-1,2,3-Triazoles from 4-(1-Adamantyl)benzyl Azide through a 1,3-Dipolar Cycloaddition Reaction Oussama Bencheikh le Hocine a Department of Chemistry, Faculty of Sciences, Université des Frères Mentouri Constantine 1, Constantine 25000, Algeria Email: dtebbani2002@yahoo.fr , Dahmane Tebbani* a Department of Chemistry, Faculty of Sciences, Université des Frères Mentouri Constantine 1, Constantine 25000, Algeria Email: dtebbani2002@yahoo.fr , Artur M. S. Silva * b QOPNA, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal Email: artur.silva@ua.pt › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract A series of new 1,4-disubstituted 1H-1,2,3-triazole derivatives were synthesized by an efficient copper-catalyzed 1,3-dipolar cycloaddition reaction of 4-(1-adamantyl)benzyl azide with several terminal alkynes. The copper catalyst was used to provide 1,4-disubstituted 1,2,3-triazoles regioselectively in good yields. Key words Key wordstriazoles - 1,3-dipolar cycloaddition - copper catalysis - one-pot process - adamantylbenzyl azide - click chemistry Full Text References References and Notes 1 Demaray JA, Thuener JE, Dawson MN, Sucheck SJ. Bioorg. Med. Chem. Lett. 2008; 18: 4868 2 Wang X.-L, Wan K, Zhou C.-H. Eur. J. Med. Chem. 2010; 45: 4631 3 Banday AH, Shameem SA, Ganai BA. Org. Med. Chem. 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Protoc. 2010; 5: 607 32 Click Synthesis of 1,2,3-Triazoles 5a–s: General Procedure Cu(OAc)2·H2O (24 mg, 0.1 equiv) and NaAsc (23 mg, 0.1 equiv) were added to a stirred solution of 4-(1-adamantyl)benzyl azide (3; 0.32 g, 1.2 mmol) and the appropriate terminal alkyne 4 (1.2 mmol) in DMF (5 mL). The mixture was then stirred for 2–3 h at r.t. until the starting material was completely consumed (TLC). Sat. brine was added to the mixture and the crude product was extracted with EtOAc (3 × 10 mL). The combined extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography [silica gel, EtOAc–PE (1:3)]. 33 {1-[4-(1-Adamantyl)benzyl]-1H-1,2,3-triazol-4-yl}methanol (5b) White solid; yield: 314 mg (81%); mp 168 °C. IR (run as NaCl discs): 3200, 1025, 2900, 2847 cm−1. 1H NMR: δ = 7.46 (s, 1 H, triazole-H), 7.39 (d, J = 8.4 Hz, 2 H, Ar-H), 7.26 (d, J = 8.3 Hz, 2 H, Ar-H), 5.48 (s, 2 H, CH2–N), 4.75 (s, 2 H, CH2–O), 2.80 (s, 1 H, OH), 2.09–2.17 (m, 3 H, ad-H), 1.92 (br d, 6 H, ad-H), 1.81–1.80 (m, 6 H, ad-H). 13C NMR: δ = 152.3 (Ar-Cq), 143.9 (triazole-Cq), 131.5 (1 C, Ar-Cq), 128.1, 125.8 (4 C, Ar-C), 121.7 (1 C, Ar-C), 120.2 (triazole-CH), 56.6 (CH2–O), 54.1 (s, CH2–N), 43.2 (3 C, CH2, ad-C), 36.8 (3 C, CH2, ad-C), 36.3 (ad-Cq), 28.9 (3 C, CH, ad-C). HRMS (ESI+): m/z [M + H]+ calcd for C20H26N3O: 324.2077; found: 324.2068. 34a Wang Q, Chan TR, Hilgraf R, Fokin VV, Sharpless KB, Finn MG. J. Am. Chem. Soc. 2003; 125: 3192 34b Meldal M, Tornøe CW. Chem. Rev. 2008; 108: 2952 Supplementary Material Supplementary Material Supporting Information
