Selective Catalytic Aerobic Photooxidation of Thioethers to Sulfoxides

Abstract

A convenient visible-light-promoted oxidation of thioethers to sulfoxides is developed utilizing eosin Y as the photocatalyst and molecular oxygen from air as the oxidant. This photochemical protocol features good functional group tolerance and excellent chemoselectivity. Under the developed mild conditions, a wide variety of sulfides are converted into the corresponding sulfoxides in excellent yields (up to 93%). Moreover, this protocol can easily be amplified to gram scale, showing good practical value.

Key words

photocatalysis - oxidation - eosin Y - sulfoxides - thioethers

Publikationsverlauf

Eingereicht: 23. Februar 2025

Angenommen nach Revision: 08. April 2025

Accepted Manuscript online:
08. April 2025

Artikel online veröffentlicht:
22. Mai 2025

• References and Notes

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• 37 Photooxidation of Sulfides to Sulfoxides To a tube equipped with a stir bar were added the corresponding thioether (1.0 mmol, 1.0 equiv), eosin Y (4 mol%), and MeCN/H₂O (2 mL/0.2 mL). The mouth of the reaction tube was open to air and the reaction mixture was stirred under irradiation with a blue LED (4.8 W) at room temperature (25 °C). After 4 h, the crude mixture was concentrated under vacuum. The residue was purified by rapid chromatography on silica gel to give sulfoxides 2a–am, 4a, and 4b.
• 38 Methyl Phenyl Sulfoxide (2a) Yield: 66 mg (93%); white solid. ¹H NMR (600 MHz, CDCl₃): δ = 7.47–7.45 (m, 2 H), 7.33–7.29 (m, 3 H), 2.51 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 145.3, 130.5, 128.9 (2 C), 123.0 (2 C), 43.5. HRESIMS: m/z [M + H]⁺ calcd for C₇H₉OS: 141.0374; found: 141.0370.
• 39 Phenyl benzenesulfinothioate (4a) Yield: 49 mg (46%); white solid. ¹H NMR (600 MHz, CDCl₃): δ = 7.59–7.55 (m, 3 H), 7.48–7.46 (m, 1 H), 7.43–7.41 (m, 2 H), 7.36–7.32 (m, 4 H). ¹³C NMR (150 MHz, CDCl₃): δ = 143.1, 136.7 (2 C), 133.8, 131.5, 129.6 (2 C), 128.9 (2 C), 128.0, 127.7 (2 C). HRESIMS: m/z [M + H]⁺ calcd for C₁₂H₁₁OS₂: 235.0251; found: 235.0564.
• 40 4-Methoxyphenyl 4-Methoxybenzenesulfinothioate (4b) Yield: 60 mg (57%); yellow solid. ¹H NMR (600 MHz, CDCl₃): δ = 7.49 (d, J = 7.8 Hz, 2 H), 7.26 (d, J = 7.2 Hz, 2 H), 6.85 (d, J = 7.2 Hz, 2 H), 6.84 (d, J = 7.8 Hz, 2 H), 3.85 (s, 3 H), 3.82 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 163.6, 162.3, 138.5 (2 C), 135.0, 130.0 (2 C), 119.0, 115.0 (2 C), 113.9 (2 C), 55.8, 55.6. HRESIMS: m/z [M + H]⁺ calcd for C₁₄H₁₅O₃S₂: 295.0463; found: 295.0460.
• 41 Gram-Scale Synthesis of Benzylmethylsulfoxide (2am) Benzyl methyl sulfide (1am) (1.10 g, 8 mmol, 1.0 equiv) and eosin Y (207.3 mg, 0.324 mmol, 4 mol%) were added to a 50 mL round-bottom flask equipped with a stir bar. MeCN/H₂O (30 mL, 10:1 v/v) was then added to dissolve solids. The reaction mixture was stirred under 4.8 W blue LEDs at room temperature for 6 h under an air atmosphere. The distance from the light source to the flask was about 5 cm. After completion of the reaction, the mixture was diluted with water (200 mL). The aqueous layer was extracted with ethyl acetate (3 × 150 mL). The combined organic layer was washed with brine, dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was further purified by column chromatography using petroleum ether and ethyl acetate as the eluent (20:1 v/v) to afford product 2am (1.10 g, 89% yield). ¹H NMR (600 MHz, CDCl₃): δ = 7.55 (d, J = 6.6 Hz, 2 H), 7.47–7.42 (m, 3 H), 2.88–2.82 (m, 1 H), 2.74–2.68 (m, 1 H), 1.13 (t, J = 1.2 Hz, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 143.3, 130.9, 129.1 (2 C), 124.1 (2 C), 50.3, 5.9. HRESIMS: m/z [M + H]⁺ calcd for C₈H₁₁OS: 155.0531; found: 155.0521.
• 42 Modafinil (6) To a tube equipped with a stir bar were added diphenylmethylthioacetamide (5) (0.39 mmol, 1.0 equiv), eosin Y (4 mol%), and MeOH/H₂O (2 mL/0.2 mL). The mouth of the reaction tube was open to air and the reaction mixture was stirred under irradiation with a blue LED (4.8 W) at room temperature (25 °C). After 4 h, the crude mixture was concentrated under vacuum. The residue was purified by rapid chromatography on silica gel to give modafinil (6) (91 mg, 86% yield) as a white solid. ¹H NMR (600 MHz, methanol-d ₄): δ = 7.90 (s, 1 H), 7.57–7.54 (m, 5 H), 7.44–7.41 (m, 5 H), 7.39–7.37 (m, 1 H), 5.35 (s, 1 H), 3.50–3.40 (m, 2 H). ¹³C NMR (150 MHz, DMSO-d ₆): δ = 166.3, 137.2, 134.9, 129.7, 129.0, 128.5, 128.0, 127.9, 68.8, 56.1. HRESIMS­: m/z [M + H]⁺ calcd for C₁₅H₁₆NO₂S: 274.0902; found: 274.0900.
• 43 Zhang JL, Wang LM, Liu Q, Yang Z, Huang Y. Chem. Commun. 2013; 49: 11662