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

Publikationsverlauf

Eingereicht: 22. September 2023

Angenommen nach Revision: 13. Dezember 2023

Accepted Manuscript online:
13. Dezember 2023

Artikel online veröffentlicht:
18. Januar 2024

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• 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.