Efficient Ligand-Free, Copper-Catalyzed N-Arylation of Sulfonamides

Abstract

An efficient and convenient protocol has been developed for the N-arylation of sulfonamides with differently substituted aryl iodides using ligand-free copper iodide to afford the arylated products in good to excellent yields (up to 91%).

Key words

ligand-free - copper - sulfonamides - N-arylation

References and Notes

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19

Representative Procedure for N-Arylation of Sulfonamides
A mixture of CuI (Sigma-Aldrich, 99.99%, 0.0735 mmol) and Cs₂CO₃ (2.94 mmol) was dissolved in DMF (0.75 mL). Then, aryl halide (2.21 mmol) and sulfonamide (1.47 mmol) were added to this reaction vial, and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 135 ˚C for 24 h, then the heterogeneous mixture was cooled to r.t. and diluted with CH₂Cl₂. The resulting solution was directly filtered through a pad of Celite. The combined organic extracts were dried with anhyd Na₂SO₄, and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chroma-tography to afford the N-arylated product. The identity and purity of the products was confirmed by ^¹H NMR and ^¹³C NMR spectroscopic analysis. Following the general procedure using p-toluenesulfonamide (1.47 mmol) and iodobenzene (2.94 mmol) provided 314 mg (86%) of the coupling product 3a as a yellowish solid after purification by flash chromatography (hexane-EtOAc, 85:15) of the crude oil. ^¹H NMR (400 MHz, CDCl₃): δ = 7.70 (d, J = 8.3 Hz, 2 H), 7.22-7.18 (m, 4 H), 7.11-7.06 (m, 3 H), 2.34 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 143.8, 136.7, 136.0, 129.6, 129.2, 127.3, 125.1, 121.3, 21.5. Anal. Calcd for C₁₃H₁₃NO₂S: C, 63.13; H, 5.30; N, 5.66; S, 12.97. Found: C, 62.68; H, 5.29; N, 5.53; S, 12.72.