Catalyst-Free One-Pot Synthesis of Novel Heteroarylamine Substituted Furo[3,2-c]coumarins

Abstract

A high-yielding cyclocondensation of 4-hydroxycoumarin, phenylglyoxal monohydrate, and heteroarylamines proceeds without catalysis, which gives novel functionalized furo[3,2-c]coumarins and heteroarylamino alkylation of coumarin products in acetonitrile under reflux, is reported for the first time. This tandem process involves sequentially an aldol condensation, Michael addition, a ring closure, and dehydration reaction.

Key words

furo[3,2-c]coumarin - phenylglyoxal monohydrate - 4-hydroxycoumarin - heteroarylamine - multicomponent reaction

• References and Notes

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• 12 General Procedure for the Synthesis of Compounds 4 and 6 A mixture of 4-hydroxycoumarin (1.0 mmol), phenylglyoxal monohydrate (1.0 mmol), and heteroarylamine (1.0 mmol) was heated in CH₃CN (10 mL) under reflux with stirring for the requisite time (Schemes 1 and 3). After completion of the reaction (monitoring by TLC), the reaction mixture was allowed to cooled room temperature and the precipitated product was separated by filtration, washed with cold CH₃CN, and dried to give the crude product. The crude product was stirred for 5 min in boiling THF, and the resulting precipitate was filtered. The final products 4 and 6 thus obtained were found to be pure upon TLC examination. Selected Analytical Data
  2-Phenyl-3-(pyridin-2-ylamino)-4H-furo[3,2-c]chromen-4-one (4a) White powder; yield 300 mg (85%); mp >350 °C. IR (KBr): 3309, 3058, 1662, 1600, 1515, 1460, 1407, 1276, 1199, 1137, 1058 cm^–1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 7.21–7.45 (m, 7 H, NH, ArH), 7.55 (t, 1 H, J = 7.5 Hz, ArH), 7.78–7.91 (m, 5 H, ArH), 8.28 (d, 1 H, J = 6.6 Hz, ArH) ppm. ¹H NMR (300 MHz, DMSO-d ₆ + D₂O): δ = 7.22–7.44 (m, 6 H, ArH), 7.55 (t, 1 H, J = 7.5 Hz, ArH), 7.73–7.88 (m, 5 H, ArH), 8.22 (d, 1 H, J = 6.6 Hz, ArH) ppm. ¹³C NMR (75 MHz, DMSO-d ₆): δ = 112.37, 116.52, 116.58, 116.65, 121.08, 122.23, 123.11, 125.43, 127.55, 127.96, 129.01, 129.27, 129.66, 132.03, 132.64, 132.68, 132.69, 139.46, 154.71, 163.09 ppm. MS (EI, 70 eV): m/z (%) = 354 (100) [M]⁺, 337, 297, 269, 234, 205, 177, 121, 78. Anal. Calcd for C₂₂H₁₄N₂O₃: C, 74.57; H, 3.95; N, 7.90. Found: C, 74.65; H, 3.86; N, 7.93. 3-[1-(6-Methylpyridin-2-ylamino)-2-oxo-2-phenylethyl]-4-hydroxy-2H-chromen-2-one (6a) White powder; yield 332 mg (83%); mp 320 °C (dec.). IR (KBr): 3216, 3058, 2919, 1700, 1654, 1504, 1415, 1338, 1249, 1103, 1045 cm^–1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.52 (s, 3 H, CH₃), 6.33 (s, 1 H, methine-H), 6.61 (d, 1 H, J = 7.2 Hz, ArH), 7.10 (d, 1 H, J = 8.1 Hz, ArH), 7.18–7.49 (m, 7 H, NH, ArH), 7.68–7.92 (m, 4 H, ArH), 9.22 (br, 1 H, OH) ppm. ¹H NMR (300 MHz, DMSO-d ₆ + D₂O): δ = 2.49 (s, 3 H, CH₃), 6.31 (s, 1 H, methine-H), 6.60 (d, 1 H, J = 6.9 Hz, ArH), 7.07 (d, 1 H, J = 8.1 Hz, ArH), 7.16–7.47 (m, 6 H, ArH), 7.67–7.92 (m, 4 H, ArH) ppm. ¹³C NMR (75 MHz, DMSO-d ₆): δ = 19.42, 55.03, 98.37, 107.75, 111.60, 116.34, 117.40, 121.47, 123.35, 125.20, 128.13, 128.57, 131.84, 133.24, 135.36, 142.40, 147.28, 153.05, 153.92, 173.39, 194.99 ppm. MS (EI, 70 eV): m/z (%) = 278 [M – 108]⁺, 249, 221, 201, 173, 121, 108, 105 (100), 92, 77. Anal. Calcd for C₂₃H₁₈N₂O₄: C, 71.50; H, 4.66; N, 7.25. Found: C, 71.44; H, 4.69; N, 7.33.
• 13 Shao J. Ke D. Shu K. Chen E. Yu Y. Chen W. Synlett 2018; 29: 922