Ligand-Free CuI-Catalyzed Chemoselective S-Arylation of 2-Mercaptobenzimidazole with Aryl Iodides

Abstract

A practical and efficient strategy for the chemoselective C–S cross-coupling of 2-mercaptobenzimidazole derivatives with a range of substituted aryl iodides is described. Under the optimized conditions of 5 mol% CuI and 100 °C, a variety of S-arylated products were obtained in good to excellent yields (up to 92 %) without the need for assisting ligands.

Key words

2-mercaptobenzimidazole - ligand-free - S-arylation - copper(I) iodide - chemoselective

• References and Notes

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• 40 General Procedure for S-Arylation of 2-Mercaptobenzimidazoles A mixture of CuI (Sigma-Aldrich, 0.025 mmol, 5 mol%), anhydrous K₃PO₄ (0.65 mmol), 2-mercaptobenzimidazole (0.5 mmol), DMSO (0.2 mL), and aryl halide (0.75 mmol) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 100 °C for 24 h. The heterogeneous mixture was subsequently cooled to room temperature and diluted with dichloromethane. The combined organic extracts were dried with anhydrous Na₂SO₄, and the solvent was removed under reduced pressure. The crude product was loaded into the column using minimal amounts of dichloromethane and was purified by silica gel column chromatography to afford the S-arylated product. The identity and purity of products was confirmed by ¹H NMR and ¹³C NMR spectroscopic analysis. 2-(Phenylthio)-1H-benzo[d]imidazole (2aa) 101 mg (90% yield) of the coupled product was obtained as an off-white solid. ¹H NMR (400 MHz, DMSO-d): δ = 12.50 (br s, 1 H), 7.62 (dd, J = 25.6, 7.6 Hz, 2 H), 7.42–7.31 (m, 7 H). ¹³C NMR (100 MHz, DMSO-d): δ = 147.6, 135.4, 131.3, 130.1, 129.6, 122.8, 118.7, 110.4. HRMS: m/z calcd [M⁺]: 227.0641; found: 227.0644. 2-[(2-Fluorophenyl)thio]-1H-benzo[d]imidazole (2ab) 105 mg (86% yield) of the coupled product was obtained as an off-white solid. ¹H NMR (400 MHz, DMSO-d): δ = 12.77 (br s, 1 H), 7.58–7.48 (m, 3 H), 7.42–7.35 (m, 2 H), 7.28 (t, J = 5.6 Hz, 1 H), 7.16 (m, 2 H). ¹³C NMR (100 MHz, DMSO-d): δ = 160.8 (d, J = 240.0 Hz), 144.7 (d, J = 220.0 Hz), 134.7, 131.4 (d, J = 3.0 Hz), 125.5 (d, J = 3.0 Hz), 122.4, 119.8 (d, J = 340.0 Hz), 116.4, 116.2, 110.9. HRMS: m/z calcd [M⁺]: 245.0546; found: 245.0547. 2-[(2-Chlorophenyl)thio]-1H-benzo[d]imidazole (2ac) 114 mg (88% yield) of the coupled product was obtained as an off-white solid. ¹H NMR (400 MHz, DMSO-d): δ = 12.96 (br s, 1 H), 7.60 (dd, J = 7.6, 1.6 Hz, 3 H), 7.40–7.29 (m, 3 H), 7.21 (s, 2 H). ¹³C NMR (100 MHz, DMSO-d): δ = 144.4, 133.1, 131.9, 131.3, 130.0, 129.4, 128.2, 122.7, 118.5, 111.3. HRMS: m/z calcd [M⁺]: 261.0251; found: 261.0249. 2-[(2-Methoxyphenyl)thio]-1H-benzo[d]imidazole (2ad) 106 mg (83% yield) of the coupled product was obtained as an off-white solid. ¹H NMR (400 MHz, DMSO-d): δ = 12.64 (br s, 1 H), 7.49 (s, 2 H), 7.36 (t, J = 7.6 Hz, 2 H), 7.24–7.11 (m, 3 H), 6.96 (t, J = 7.6 Hz, 1 H), 3.82 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d): δ = 157.1, 146.3, 131.8, 129.7, 121.9, 121.3, 119.3, 111.9, 106.1, 56.0. HRMS: m/z calcd [M⁺]: 257.0746; found: 257.0743.