Regiospecific Synthesis of Novel Furo[4,5-c]coumarins in a One-Pot Reaction

Abstract

A new and expedient assembly of an interesting class of amido-substituted furo[4,5-c]coumarins has been successfully achieved through a one-pot sequential coupling and cyclization strategy starting from 4-hydroxycoumarin, aryl glyoxals and benz­amide. All the reactions showed selectivity towards furo[4,5-c]coumarin, instead of the corresponding isoxazolo-substituted coumarins.

Key words

library construction - coumarins - glyoxals - benzamide

• References and Notes

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• 22 Synthesis of 2-Phenyl-3-benzamidofuro[4,5-c]coumarin (4a); Typical Procedure: A solution of phenylglyoxal monohydrate (1 mmol) and benzamide (1.1 mmol) in AcOH (10 mL) was stirred and heated at 70 °C for 30 min, then the 4-hydroxycoumarin (1 mmol) was added. The reaction mixture was heated at reflux (110 °C) and the progress of the reaction was monitored by TLC (EtOAc–hexane, 1:1). Upon completion, the reaction mixture was poured onto ice, and the precipitate was filtered off and thoroughly washed with water. The pure product 4a (85%) was obtained by recrystallization from EtOH as pale-yellow crystals; mp 216–218 °C. IR (KBr): 3347, 2924, 1678, 1613, 1565, 1344 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.75 (s, 1 H), 8.02 (d, J = 7.6 Hz, 1 H), 7.92 (d, J = 7.2 Hz, 2 H), 7.88 (d, J = 8.0 Hz, 2 H), 7.65 (t, J = 7.6 Hz, 1 H), 7.57–7.45 (m, 5 H), 7.38 (t, J = 8.0 Hz, 2 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 166.5, 163.5, 161.6, 152.4, 135.3, 133.5, 132.9, 131.6, 131.6, 128.6, 128.3, 128.2, 127.5, 127.4, 124.2, 123.8, 116.5, 115.9, 102.1. Anal. Calcd for C₂₄H₁₅NO₄: C, 75.58; H, 3.96; N, 3.67. Found: C, 75.69; H, 3.87; N, 3.61. MS: m/z = 381.1.