A Metal-Free and Microwave-Assisted Efficient Synthesis of Diaryl Sulfones

Abstract

An efficient and general protocol for the synthesis of diaryl sulfones via the metal-free coupling of readily available diaryliodonium salts and arenesulfinates in PEG-400 under microwave irradiation has been developed. Utilizing this metal-free and eco-friendly protocol, we have prepared various diaryl sulfones in high yields and shorter reaction times under mild conditions. Furthermore, the coupling of diaryliodonium with arenesulfinate salts with and without copper iodide provides a convenient access to various diaryl sulfones with high selectivity.

Key words

diaryl sulfones - diaryliodonium salts - arenesulfinate salts - microwave irradiation - polyethylene glycol (PEG-400)

• References and Notes

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• 23 General Procedure for the Synthesis of Diaryl Sulfones 5 The diaryliodonium salts were prepared according to the reported methods.²⁹ A mixture of diaryliodonium salt 3a–h (0.2 mmol) and arenesulfinate salt 4a–c (0.2 mmol) in PEG-400 (0.1 mL) was placed in a sealed microwave vial and irradiated in MW (power 200 W) at 50 °C for 10 min. After completion, H₂O (1 mL) was added, and the reaction mixture was extracted with EtOAc (3 × 5 mL). The combined organic extract was washed with H₂O (4 mL) and dried over anhyd Na₂SO₄. The solvent was evaporated in vacuo, the solid thus obtained was washed with hexane and dried to afford 8a–m in high yields.
• 24 General Procedure for the Copper-Catalyzed Preparation of Diaryl Sulfones 5 A mixture of diaryliodonium salts 3e–g (0.2 mmol) and sodium p-toluenesulfinate 4a (0.2 mmol) in PEG-400 (0.1 mL). A catalytic amount of CuI (10 mol%) was added, and the reaction mixture was placed in a sealed microwave vial and irradiated in MW (power 200 W) at 50 °C for 15 min. After completion of the reaction, 20% Na₂CO₃ solution (2 mL) was added. The aqueous layer was extracted with EtOAc (3 × 5 mL), washed with H₂O (7 mL), and dried over anhyd. Na₂SO₄. The solvents were evaporated under reduced pressure, and the residue so obtained was purified by column chromatography on silica gel (100–120 mesh) eluting with hexane–EtOAc (4:1) afforded the desired diaryl sulfones 5. Spectral Data for Selected Compounds
  Phenyl Tolyl Sulfone (5a) Yield 96%; white solid; mp 119–121 °C (lit.⁷ mp 119–122 °C). IR (KBr): 1303, 1149 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.36 (s, 3 H), 7.34 (d, 2 H, J = 8.0 Hz), 7.58–7.50 (m, 3 H), 7.76 (d, 2 H, J = 8.1 Hz), 7.87 (d, 2 H, J = 7.3 Hz). ESI-MS: m/z calcd for C₁₃H₁₃O₂S [M + H]⁺: 233.1; found: 233.1. Bistolyl Sulfone (5b) Yield 92%; white solid; mp 157–159 °C (lit.⁷ mp 158–159 °C). IR (KBr): 1288, 1149 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.35 (s, 6 H,), 7.29 (d, 4 H, J = 8.0 Hz), 7.72 (d, 4 H, J = 7.7 Hz), ESI-MS: m/z calcd for C₁₄H₁₅O₂S [M + H]⁺: 247.1; found: 247.2. p -Bromophenyl Tolyl Sulfone (5c) Yield 82%; white solid; mp 131–133 °C (lit.¹ mp 132–134 °C). IR (KBr): 1319, 1149 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.36 (s, 3 H) 7.38 (d, 2 H, J = 8.1 Hz), 7.62 (d, 2 H, J = 8.6 Hz), 7.83–7.74 (4 H, m). ESI-MS: m/z calcd for C₁₃H₁₂BrO₂S [M + H]⁺: 313.0; found: 313.0. p -Chlorophenyl Tolyl Sulfone (5d) Yield 83%; white solid; mp 116–118 °C (lit.¹ mp 119–120 °C). IR (KBr): 1319, 1149 cm^–1. ESI-MS: m/z calcd for C₁₃H₁₂ClO₂S [M + H]⁺: 267.0; found: 267.1. 2,4,6-Trimethylphenyl Tolyl Sulfone (5e) Yield 89%; white solid; mp 116–117 °C (lit.³⁰ mp 115–117 °C). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 143.18, 142.89, 139.90, 139.07, 133.60, 131.84, 129.25, 125.67, 22.18, 21.03, 20.42. ESI-MS: m/z calcd for C₁₆H₁₉O₂S [M + H]⁺: 275.1; found: 275.2. p -Tolylsulfonylbenzoic Acid (5f) Yield 91%; white solid; mp 120–121 °C. IR (KBr): 3055-2553, 1689, 288, 1157 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.33 (3 H, s,), 7.31 (2 H, d, J = 7.5 Hz), 7.76 (2 H, d, J = 7.5 Hz), 7.93 (2 H, d, J = 7.9 Hz), 8.07 (2 H, d, J = 7.7 Hz). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 165.94, 144.85, 144.37, 137.27, 134.90, 130.13, 129.85, 127.35, 127.01, 20.67. p -Fluorophenyl Tolyl Sulfone (5g) Yield 88%; white solid; mp 85–87 °C (lit.¹ mp 85–86 °C). ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.35 (s, 3 H), 7.47–7.42 (m, 4 H), 7.85 (d, 2 H, J = 6.6 Hz), 8.04 (dd, 2 H, J = 9.0, 5.1 Hz). Diphenyl Sulfone (5h) Yield 88%; white solid; mp 128–130 °C (lit.⁷ mp 127–129 °C). IR (KBr): 1303, 1149 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.59–7.51 (m, 6 H), 7.89 (d, 4 H, J = 8.6 Hz). p -Chlorophenyl Phenyl Sulfone (5j) Yield 96%; white solid; mp 77–79 °C (lit.³⁰ mp 77–78 °C). ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.64 (d, 2 H, J = 7.8 Hz), 7.71 (d, 3 H, J = 8.6 Hz), 7.98 (d, 4 H, J = 8.2 Hz). ESI-MS: m/z calcd for C₁₂H₁₀ClO₂S [M + H]⁺: 253.0; found: 253.1. 2,4,6-Trimethylphenyl Phenyl Sulfone (5k) Yield 91%; white solid; mp 78–80 °C (lit.³⁰ mp 79–81 °C). ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.30 (s, 3 H), 2.56 (s, 6 H), 7.11 (s, 2 H), 7.42 (t, 2 H, J = 7.8 Hz), 7.53 (t, 1 H, J = 7.4 Hz), 7.73 (d, 2 H, J = 7.7 Hz). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 143.33, 141.25, 133.16, 131.58, 131.30, 129.72, 121.68, 113.42, 26.45, 20.21. ESI-MS: m/z calcd for C₁₅H₁₇O₂S [M + H]⁺: 261.1; found: 261.1 2-Thienyl Tolyl Sulfone (5l) Yield 82%; white solid; mp 116–118 °C (lit.⁷ mp 118–120 °C). ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.34 (s, 3 H), 7.30 (d, 2 H, J = 8.0 Hz), 7.50–7.46 (m, 2 H, J = 7.4 Hz), 7.75 (d, 2 H, J = 8.0 Hz), 7.84 (d, 1 H, J = 7.5 Hz). Methyl Phenyl Sulfone (5m) Yield 83%; white solid; mp 145–146 °C (lit.⁸ mp 144–145 °C). ¹H NMR (400 MHz, DMSO-d ₆): δ = 3.12 (s, 3 H), 7.63 (t, 2 H, J = 8.17 Hz), 7.71 (t, 1 H, J = 5.4 Hz), 7.94 (d, 2 H, J = 7.2 Hz). Methyl p-Tolyl Sulfone (5n) Yield 83%; white solid: mp 87 °C (lit.^6a mp 144–145 °C). ¹H NMR (400 MHz, DMSO-d ₆): δ = 2.44 (s, 3 H), 3.12 (s, 3 H), 7.43 (d, 2 H, J = 8.0 Hz), 7.80 (d, 2 H J = 8.1 Hz). Methyl p-Methoxyphenyl Sulfone (5p) Yield 84%; white solid: mp 119 °C (lit.^6a mp 118–120 °C). ¹H NMR (400 MHz, DMSO-d ₆): δ = 3.10 (s, 3 H), 3.87 (s, 3 H), 7.12 (d, 2 H, J = 8.8 Hz), 7.85 (d, 2 H, J = 8.8 Hz).
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