H₂O₂-Promoted Alkylation of Quinoxalin-2(1H)-ones with Styrenes and Dimethyl Sulfoxide

Abstract

A hydrogen peroxide (H₂O₂)-mediated quinoxaline-2(1H)-ones hydrocarbylation reaction has been reported. The reaction is achieved through the difunctionalization of styrene. In this transformation, methyl radical resulting from dimethyl sulfoxide firstly attacks styrenes to provide alkyl radicals which then undergo alkylation at the C3 position of quinoxalin-2(1H)-one. A green, convenient, and simple protocol for the synthesis of 3-alkylquinoxalin-2(1H)-ones was provided.

Key words

hydrocarbylation - quinoxaline-2(1H)-ones - difunctionalization

Publikationsverlauf

Eingereicht: 23. April 2021

Angenommen nach Revision: 12. Mai 2021

Accepted Manuscript online:
12. Mai 2021

Artikel online veröffentlicht:
14. Juni 2021

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• 11 Hydrocarbylation Products 3 – General Procedure Quinoxalin-2(1H)-ones 1 (0.3 mmol), styrene 2 (2 equiv), H₂O₂ (30% in water, 3 equiv), and DMSO (2 mL) were mixed and stirred at 120 ℃ in a sealed tube under N₂ for 12 h. After completion of the reaction, the reaction mixture was cooled to room temperature, water (10 mL) was added, followed by extraction diluted with ethyl acetate (3 × 10 mL). The combined organic portion was dried with anhydrous Na₂SO₄ and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a mixture of petroleum ether and ethyl acetate as eluent to afford various target compounds. Compound 3a was obtained in 81% yield (67.8 mg) according to the general procedure as a white solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.92 (dd, J = 8.0, 1.5 Hz, 1 H), 7.53–7.48 (m, 1 H), 7.47–7.43 (m, 2 H), 7.37–7.31 (m, 1 H), 7.29–7.23 (m, 3 H), 7.19–7.14 (m, 1 H), 4.58 (t, J = 7.7 Hz, 1 H), 3.62 (s, 3 H), 2.32 (m, 1 H), 2.09 (m, 1 H), 0.92 (t, J = 7.4 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 161.39, 154.65, 141.63, 133.00, 132.83, 130.13, 129.64, 128.70, 128.25, 126.51, 123.39, 113.44, 49.15, 29.10, 27.10, 12.42. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₈H₁₈N₂O: 279.1492; found: 279.1488.
• 12 Hydrocarbylation Products 4 – General Procedure Quinoxalin-2(1H)-ones 1 (0.3 mmol), styrene 2 (2 equiv), H₂O₂ (30% in water, 3 equiv), and DMSO (2 mL) were mixed and stirred at 120 °C in a sealed tube under N₂ for 12 h. After completion of the reaction, the reaction mixture was cooled to room temperature, water (10 mL) was added, followed by extraction diluted with ethyl acetate (3 × 10 mL). The combined organic portion was dried with anhydrous Na₂SO₄ and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a mixture of petroleum ether and ethyl acetate as eluent to afford various target compounds. Compound 4e was obtained in 72% yield (63.2 mg) according to the general procedure as a colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.95 (dd, J = 8.0, 1.5 Hz, 1 H), 7.51 (t, J = 7.8 Hz, 1 H), 7.37–7.33 (m, 1 H), 7.27–7.25 (m, 1 H), 7.22 (d, J = 2.7 Hz, 1 H), 7.17 (dd, J = 6.5, 2.4 Hz, 1 H), 7.07–7.03 (m, 2 H), 4.81 (t, J = 7.5 Hz, 1 H), 3.61 (s, 3 H), 2.64 (s, 3 H), 2.31–2.27 (m, 1 H), 2.04–1.99 (m, 1 H), 0.93 (t, J = 7.3 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 161.66, 140.20, 137.16, 132.75, 130.32, 130.09, 129.58, 126.94, 126.20, 125.72, 123.37, 113.44, 44.29, 29.07, 27.65, 20.05, 12.31. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₉H₂₀N₂O: 293.1648; found: 293.1641.