Cu-FeCl₃-Mediated One-Pot Multicomponent Reaction Leading to N-Aryl- and N-Alkyltriazoles in Water [1]

Abstract

A concise, convenient and mild route for the one-pot syntheses of N-aryl- and N-alkyltriazoles in water is reported. The methodology involves the three-component reaction comprising phenylacetylene, sodium azide and aryl/alkyl halide catalyzed by Cu(I) species generated in situ by a redox reaction between FeCl₃ and copper metal. Prominent features of our methodology are in­corporation of aryl fluoride to generate N-aryltriazoles, which are rather scarcely reported, use of water as reaction medium, and avoidance of hazardous aryl azide as a reactant.

multicomponent reaction - triazole - Cu-FeCl₃ - redox reaction

References and Notes

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19

General Procedure for the Preparation of 1-(2-Nitrophenyl)-4-phenyl-1 H -[1,2,3]triazole ( 3a): 1-Fluoro-2-nitrobenzene (2.0 mmol), phenylacetylene (2.2 mmol), sodium azide (2.2 mmol) and NaHCO₃ (2.2 mmol) were suspended in H₂O (10 mL) in a 50-mL round-bottomed flask equipped with a small magnetic stirring bar. To this was added copper powder (100 mg) and ferric chloride (100 mg). The mixture was then heated to reflux for 7 h. The reaction mixture was cooled and EtOAc (50 mL) was added. The suspension was passed through a bed of celite and the filtrate was partitioned in a separating funnel. The organic layer was separated, dried (Na₂SO₄) and concentrated to afford a residue, which was purified by silica gel chromatography using hexane-EtOAc (70:30) as eluent to afford 3a as a yellow solid. Yield: 72%; mp 144-145 °C. IR (KBr): 1604, 1534, 1351 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.12 (dd, J = 1.2, 7.9 Hz, 1 H, ArH), 8.09 (s, 1 H, ArH), 7.91-7.94 (m, 2 H, ArH), 7.81-7.84 (m, 1 H, ArH), 7.69-7.76 (m, 2 H, ArH), 7.46-7.51 (m, 2 H, ArH), 7.40-7.43 (m, 1 H, ArH). ¹³C NMR (75.5 MHz, CDCl₃): δ = 148.54, 144.60, 134.01, 130.91, 130.41, 129.96, 129.11, 128.81, 128.03, 126.15, 125.73, 121.18. MS (ES⁺): m/z = 267.1 [M⁺ + 1]. Anal. Calcd for C₁₄H₁₀N₄O₂: C, 63.15; H, 3.79; N, 21.04. Found: C, 63.26; H, 3.57; N, 21.40.
1-(4-fluoro-2-nitrophenyl)-4-phenyl-1H-[1,2,3]triazole (3b): Yield: 75%; mp 178-180 °C. IR (KBr): 1601, 1523, 1347 cm^-1. ¹H NMR (300 MHz, DMSO): δ = 9.14 (s, 1 H, ArH), 8.28 (dd, J = 2.4, 8.0 Hz, 1 H, ArH), 8.04-8.08 (m, 1 H, ArH), 7.89-7.94 (m, 3 H, ArH), 7.51 (t, J = 7.2 Hz, 2 H, ArH), 7.27-7.42 (m, 1 H, ArH), ¹³C NMR (75.5 MHz, DMSO): δ = 147.08, 144.75, 129.78, 129.60, 129.03, 128.43, 125.79, 125.37, 122.91, 121.60, 121.30, 113.80, 113.42. MS (ES⁺): m/z = 285.2.