Ligand-Free Copper(I) Chloride Catalyzed N-Arylation of 1,2,4-Triazole with Aryl Bromides

Abstract

An efficient protocol was developed for the N-arylation of 1,2,4-triazole by using substituted aryl bromides catalyzed by CuCl under ligand-free conditions. This method afforded the products in good to excellent yields (up to 88%) under the optimized conditions.

Key words

triazoles - copper catalysis - arylation - bromobenzene - ligand-free - N-heterocycles

Publication History

Received: 22 September 2023

Accepted after revision: 13 December 2023

Accepted Manuscript online:
13 December 2023

Article published online:
18 January 2024

• References and Notes

• 1a Oshiro Y, Sato S, Kurahashi N, Tanaka T, Kikuchi T, Tottori K, Uwahodo Y, Nishi T. J. Med. Chem. 1998; 41: 658
• 1b Belfield AJ, Brown GR, Foubister AJ. Tetrahedron 1999; 55: 11399
• 1c Tao C.-Z, Li J, Fu Y, Liu L, Guo Q.-X. Tetrahedron Lett. 2008; 49: 70
• 1d Romero M, Harrak Y, Basset J, Orúe JA, Pujol MD. Tetrahedron 2009; 65: 1951
• 1e Monnier F, Taillefer M. Angew. Chem. Int. Ed. 2009; 48: 6954
• 2 Olesiejuk M, Kudelko A, Świątkowski M. Materials 2020; 13: 5627
• 3 Aggarwal R, Sumran G. Eur. J. Med. Chem. 2020; 205: 112652
• 4 Kaur R, Ranjan Dwivedi A, Kumar B, Kumar V. Anti-Cancer Agents Med. Chem. 2016; 16: 465
• 5 Liao L, Jiang C, Chen J, Shi J, Li X, Wang Y, Zhang J. Eur. J. Med. Chem. 2020; 190: 112114
• 6 Chu X.-M, Wang C, Wang W.-L, Liang L.-L, Liu W, Gong K.-K, Sun K.-L. Eur. J. Med. Chem. 2019; 166: 206
• 7 Cao X, Wang W, Wang S, Bao L. Eur. J. Med. Chem. 2017; 139: 718
• 8 Chang L, Xiao M, Yang L, Wang S, Wang S.-Q, Bender A, Hu A, Zhen Z.-S, Yu B, Liu H.-M. Bioorg. Med. Chem. 2018; 26: 5006
• 9a Ma H.-C, Jiang X.-Z. J. Org. Chem. 2007; 72: 8943
• 9b Guo X, Rao HH, Fu H, Jiang YY, Zhao YF. Adv. Synth. Catal. 2006; 348: 2197
• 9c Huang Y.-Z, Gao J, Ma H, Miao H, Xu J. Tetrahedron Lett. 2008; 49: 948
• 9d Haneda S, Adachi Y, Hayashi M. Tetrahedron 2009; 65: 10459
• 9e Xu H. Mini-Rev. Org. Chem. 2009; 6: 367
• 9f Verma AK, Singh J, Larock RC. Tetrahedron 2009; 65: 8434
• 9g Rao RK, Naidu AB, Jaseer EA..Sekar G. Tetrahedron 2009; 65: 4619
• 10 Antilla JC, Baskin JM, Barder TE, Buchwald SL. J. Org. Chem. 2004; 69: 5578
• 11 Taywade A, Chavan S, Ulhe A, Berad B. Synth. Commun. 2018; 48: 1443
• 12 Song R.-J, Deng C.-L, Xie Y.-X, Li J.-H. Tetrahedron Lett. 2007; 48: 7845
• 13a Bai D.-X, Lim RS.-E, Ng H.-F, Teo Y.-C. Synth. Commun. 2021; 51: 1398
• 13b Teo Y.-C, Tan Y.-R, Saanvi K, Loh C.-K, Tan S.-N. Synth. Commun. 2023; 53: 1143
• 14 1-Phenyl-1H-1,2,4-triazole (Table [2], Entry 1); Typical Procedure A reaction vial was charged sequentially with CuCl (0.030 g, 0.30 mmol, 20 mol%), K₃PO₄ (0.637 g, 3.0 mmol, 2.0 equiv), 1,2,4-triazole (0.104 g, 1.5 mmol, 1.0 equiv), DMF (750 μL), and PhBr (529 μL, 4.5 mmol, 3.0 equiv). The vial was sealed tightly with a screw cap and its contents were mixed for 5 min at r.t. then stirred and heated in a silicone oil bath in a closed system under air at 135 °C for 18 h. The mixture was then cooled to r.t. and diluted with CH₂Cl₂ (3 × 10 mL). The resulting mixture was dried (Na₂SO₄), filtered, and concentrated under a vacuum. The crude product was collected and purified by column chromatography (silica gel) to give a white solid; yield: 154.6 mg (71%). ¹H NMR (400 MHz, CDCl₃): δ = 8.56 (s, 1 H), 8.11 (s, 1 H), 7.68 (d, J = 8.4 Hz, 2 H), 7.52 (t, J = 7.8 Hz, 2 H), 7.41 (t, J = 7.4 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 152.6, 140.9, 137.0, 129.8, 128.3, 120.1. Anal. Calcd for C₈H₇N₃: C, 66.19; H, 4.86; N, 28.95. Found: C, 65.75; H, 5.05; N, 28.73. 1-(3-Chlorophenyl)-1H-1,2,4-triazole (Table [2], Entry 6) White solid; yield: 237 mg (88%). ¹H NMR (400 MHz, CDCl₃): δ = 8.56 (s, 1 H), 8.11 (s, 1 H), 7.73 (t, J = 2.2 Hz, 1 H), 7.57–7.59 (m, 1 H), 7.45 (t, J = 8.0 Hz, 1 H), 7.36–7.39 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 152.9, 140.9, 137.9, 135.7, 130.9, 128.3, 120.4, 117.9. Anal. Calcd for C₈H₆ClN₃: C, 53.50; H, 3.37; N, 23.40. Found: C, 53.94; H, 3.53; N, 23.31.