An Efficient Approach to the Synthesis of Coumarin-Bearing 2,3-Dihydro-4(1H)-Quinazolinone Derivatives Using a Piperidine and Molecular Iodine Dual-Catalyst System

Abstract

An efficient dual-catalyst system of piperidine and molecular iodine has been developed for the synthesis of 2-alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone derivatives by a four-component reaction of salicylaldehydes, β-keto esters, ammonium acetate, and isatoic anhydride. Good yields, mild reaction conditions, and easy purification are attractive features of the present method.

Key words

salicylaldehyde - β-keto ester - isatoic anhydride - ammonium acetate - 2-alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone - dual-catalyst system

• References and Notes

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• 25 To a solution of isatoic anhdyride (1 mmol) in DMF (2 mL) was added NH₄OAc (1 mmol), and the solution was stirred for 15 min at 60 °C. Then, salicylaldehyde 1 (1 mmol), β-keto ester 2 (1 mmol), and piperidine (0.1 mmol) were added, and the solution was stirred. After 10 min molecular iodine (0.15 mmol) was added to the reaction mixture, and the reaction was stirred about 5 h. Upon completion (monitored by TLC) the solvent was evaporated under reduced pressure, and the residue was recrystallized from EtOH to afford the pure product 3a–h. 2-Methyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone (3a) White powder; 0.257 g, 84% yield; mp 298 °C (decomp.). IR (KBr): 3441 and 3169 (2 NH), 1717 (C=O), 1664 (CONH), 1609, 1570 and 1525 (Ar), 1199 (CO) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 1.81 (s, 3 H, CH₃), 6.65 (t, ³ J _HH = 7.6 Hz, 1 H, CH of Ar), 6.86 (d, ³ J _HH = 8.0 Hz, 1 H, CH of Ar), 7.18 (s, 1 H, NH), 7.24 (td, ³ J _HH = 7.6 Hz, ⁴ J _HH = 1.6 Hz, 1 H, CH of Ar), 7.33 (t, ³ J _HH = 7.6 Hz, 1 H, CH of Ar), 7.39 (d, ³ J _HH = 8.4 Hz, 1 H, CH of Ar), 7.56 (d, ³ J _HH = 8.0 Hz, 1 H, CH of Ar), 7.60 (td, ³ J _HH = 7.6 Hz, ⁴ J _HH = 1.6 Hz, 1 H, CH of Ar), 7.73 (dd, ³ J _HH = 7.6 Hz, ⁴ J _HH = 1.2 Hz, 1 H, CH of Ar), 7.84 (1 H, s, CH⁴ of coumarin), 8.46 (s, 1 H, NH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 26.5 (CH₃), 69.2 (C² of quinazoline), 114.1 (C³ of coumarin), 114.6 (CH of Ar), 115.9 (CH of Ar), 117.5 (CH of Ar), 118.0 (C^4a of coumarin), 124.8 (CH of Ar), 127.2 (CH of Ar), 128.7 (CH of Ar), 131.0 (C^4a of quinazoline), 132.1 (CH of Ar), 133.5 (CH of Ar), 138.6 (CH⁴ of coumarin), 146.2 (C^8a of quinazoline), 152.7 (C^8a of coumarin), 159.0 (CO₂), 163.2 (CONH). MS: m/z = 264, 173, 145, 132, 118, 101, 89, 63. Anal. Calcd for C₁₈H₁₄N₂O₃: C, 70.58; H, 4.61; N, 9.15. Found: C, 70.81; H, 4.69; N, 8.99. 2-(8-Methoxy-2-oxo-2H-chromen-3-yl)-2-methyl-2,3-dihydro-4(1H)-quinazolinone (3b) Beige powder; 0.259 g, 77% yield; mp 247–249 °C. IR (KBr): 3345 and 3188 (2 NH), 1706 (C=O), 1650 (CONH), 1612 and 1478 (Ar), 1276 and 1184 (CO) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 1.81 (s, 3 H, CH₃), 3.88 (s, 3 H, OCH₃), 6.65 (t, ³ J _HH = 7.4 Hz, 1 H, CH of Ar), 6.85 (d, ³ J _HH = 8.0 Hz, 1 H, CH of Ar), 7.17 (s, 1 H, NH), 7.24–7.29 (m, 4 H, CH of Ar), 7.56 (dd, ³ J _HH = 7.8 Hz, ⁴ J _HH = 1.4 Hz, 1 H, CH of Ar), 7.81 (s, 1 H, CH⁴ of coumarin), 8.44 (s, 1 H, NH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 26.4 (CH₃), 56.1 (OCH₃), 69.2 (C² of quinazoline), 114.1 (C³ of coumarin), 114.3 (CH of Ar), 114.6 (CH of Ar), 117.5 (CH of Ar), 118.6 (C^4a of coumarin), 119.8 (CH of Ar), 124.8 (CH of Ar), 127.2 (CH of Ar), 131.2 (C^4a of quinazoline), 133.5 (CH of Ar), 138.8 (CH⁴ of coumarin), 142.1 (C^8a of coumarin), 146.1 (C^8a of quinazoline), 146.2 (C _ipso -OCH₃), 158.7 (CO₂), 163.2 (CONH). MS: m/z (%) = 336 (5) [M⁺], 321 (67), 161 (100), 120 (76), 92 (81), 76 (26), 65 (43). Anal. Calcd for C₁₉H₁₆N₂O₄: C, 67.85; H, 4.79; N, 8.33. Found: C, 77.69; H, 4.88; N, 8.21.
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