Unusual Product from Condensative Cyclization: Pyrano[3,2-f]quinolin-3,10-diones from 6-Amino-5-[(trimethylsilyl)ethynyl]-2H-chromen-2-one and Aryl Aldehydes

Abstract

A new efficient and simple route for the synthesis of 8,9-dihydro-3H-pyrano[3,2-f]quinoline-3,10(7H)-dione derivatives has been accomplished via sulfuric acid promoted condensation-­cyclization of 6-amino-5-[(trimethylsilyl)ethynyl]-2H-chromen-2-one and aromatic aldehydes. The products can be oxidized to the corresponding 10-methoxy-8-aryl-3H-pyrano[3,2-f]quinolin-3-one derivatives by FeCl₃˙6H₂O in methanol.

Key words

condensation-cyclization - 8,9-dihydro-3H-pyrano[3,2-f]-quinoline-3,10(7H)-dione - iron(III) chloride - 10-methoxy-8-phenyl-3H-pyrano[3,2-f]quinolin-3-one

References and Notes

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16

General Procedure for the Preparation of Compound 5a A mixture of 6-amino-5-[(trimethylsilyl)ethynyl]-2H-chromen-2-one (3, 50 mg, 0.194 mmol), benzaldehyde (4a, 21 mg, 0.194 mmol) and concd H₂SO₄ (19 mg, 0.194 mmol) was refluxed in MeOH for 2.5 h. After completion of the reaction as monitored by TLC, the reaction mixture was cooled, and the solvent was removed under vacuum and diluted with H₂O (50 mL). The mixture was extracted with EtOAc (3 × 25 mL). The combined organic extract was washed with a sat. solution of NaHCO₃, followed by brine solution, and dried over anhyd Na₂SO₄. The solvent was distilled off. The crude product was purified by column chromatography over silica gel (60-120 mesh) using PE-EtOAc (75:25) mixture as eluent to give 8-phenyl-8,9-dihydro-3H-pyrano[3,2-f]quinoline-3,10 (7H)-dione (5a); yield 77%, orange color solid; mp 160-162 ˚C. IR (KBr): ν_max = 1299, 1656, 1713, 3318 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 2.72-2.78 (m, 1 H), 2.87 (dd, J = 14.0, 16.0 Hz, 1 H), 4.69 (s, 1 H), 4.71 (dd, J = 4.0, 14.0 Hz, 1 H), 6.41 (d, J = 10.0 Hz, 1 H), 6.83 (d, J = 9.2 Hz, 1 H), 7.25 (d, J = 9.2 Hz, 1 H), 7.28-7.40 (m, 5 H), 9.28 (d, J = 10.0 Hz, 1 H) ppm. ^¹³C NMR (100 MHz): δ = 47.1, 58.0, 110.7, 117.8, 118.2, 120.9, 124.4, 126.5, 128.7, 129.1, 140.0, 142.1, 148.0, 150.1, 160.3, 194.3 ppm. MS: m/z = 292.1 [M + H]⁺. Anal. Calcd (%) for C₁₈H₁₃NO₃: C, 74.22; H, 4.50; N, 4.81. Found: C, 74.49; H, 4.43; N, 4.70.

17

General Procedure for the Preparation of Compound 6a A solution of 8-phenyl-8,9-dihydro-3H-pyrano[3,2-f]quinoline-3,10 (7H)-dione (5a, 50 mg, 0.172 mmol) in MeOH (15 mL), FeCl₃˙6H₂O (116 mg, 0.430 mmol) was added, and the mixture was refluxed on a water bath for 4 h. After completion of the reaction as monitored by TLC, the reaction mixture was cooled and diluted with H₂O (50 mL). This was extracted with EtOAc (3 × 25 mL). The combined organic extract was washed with brine solution and dried over anhyd Na₂SO₄. The solvent was distilled off. The resulting crude product was purified by column chromatog-raphy over silica gel (60-120 mesh) using PE-EtOAc mixture (1:1) as eluent to give 10-methoxy-8-phenyl-3H-pyrano[3,2-f]quinolin-3-one (6a); yield 99%; pale yellow solid; mp 224-226 ˚C. IR (KBr): ν_max = 1297, 1563, 1704, 3356 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 4.22 (s, 3 H), 6.52 (d, J = 10.0 Hz, 1 H), 7.40 (s, 1 H), 7.47-7.57 (m, 3 H), 7.67 (d, J = 9.2 Hz, 1 H), 8.12-8.15 (m, 2 H), 8.26 (d, J = 9.6 Hz, 1 H), 9.31 (d, J = 10.0 Hz, 1 H) ppm. ^¹³C NMR (100 MHz, CDCl₃): δ = 55.9, 100.7, 113.1, 115.2, 115.4, 121.0, 127.3, 128.9, 129.7, 134.7, 139.0, 143.8, 147.5, 153.9, 158.1, 160.3, 164.3 ppm. HRMS: m/z calcd for C₁₉H₁₃NO₃ [M + H]⁺: 304.0968; found: 304.0938.