A Novel Condensation–Cyclization Reaction of 4-Chloro-3-formylcoumarin with Amidoximes: Facile Synthesis of Coumarin-Fused Pyrimidinones

Abstract

Coumarin-fused heterocyclic compounds are important materials with wide applications in biological and drug design. We report here a novel condensation–cyclization reaction of 4-chloro-3-formylcoumarin with amidoximes. The reaction gave a novel conjunction and hybrid compound of coumarin with pyrimidinones. Condensation–cyclization reactions of amidoximes with 4-chloro-3-formylcoumarin under catalyst-free conditions gave various coumarin derivatives of pyrimidinones in good to excellent yield.

Key words

coumarins - amidoximes - condensation–cyclization - pyrimidines - 4-chloro-3-formylcoumarin

• References and Notes

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• 26 Amidoximes 1 were synthesized in high yields according to our reported method consisting of addition of hydroxylamine to the nitrile group in alcohol solution (see NMR spectra in the Supporting Information).²⁴ The 4-chloro-3-formylcoumarin (2) was synthesized according to our reported method.²⁸
• 27 General Procedure for the Condensation Cyclization Reaction of Amidoxime 1 with 4-Chloro-3-formylcoumarin (2) Amidoxime 1 (1 mmol) was added to a solution of 4-chloro-2-oxo-2H-chromene-3-carbaldehyde (2, 1 mmol) in DMF (2 mL). The reaction mixture stirred at 80 °C for 2 h and then cooled to room temperature. Ice-water (3 mL) was added to the reaction mixture, and the formed solid was filtrated. The obtained solid was washed with ethyl acetate (3 × 2 mL) and dried on air. All products are pure and gave satisfactory spectral data in accordance with the assigned structures (see the Supporting Information). 2-Phenyl-3H-chromeno[4,3-d]pyrimidine-4,5-dione (3a) Yellow solid (94%, 270 mg, 237–239 °C). ¹H NMR (400 MHz, DMSO-d ₆): δ = 9.15 (s, 1 H), 8.66–8.62 (m, 2 H), 8.49 (dd, J = 8.0, 1.7 Hz, 1 H), 7.78 (ddd, J = 8.6, 7.3, 1.6 Hz, 1 H), 7.74–7.68 (m, 1 H), 7.67–7.61 (m, 2 H), 7.56 (dtd, J = 8.1, 3.6, 1.1 Hz, 2 H).¹³C{¹H} NMR (101 MHz, DMSO-d ₆): δ = 159.5, 157.9, 152.9, 146.0, 144.2, 133.9, 132.8, 131.3, 130.9, 128.6, 125.9, 124.8, 117.8, 117.7, 115.4. HRMS (ESI): m/z calcd for C₁₇H₁₀N₂O₃Na [M + Na]: 313.0589; found: 313.0587.
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