A Novel Three-Component, One-Pot Synthesis of 1,2-Dihydro-1-aryl­naphtho[1,2-e][1,3]oxazine-3-one Derivatives under Microwave-Assisted and Thermal Solvent-Free Conditions

Abstract

1,2-Dihydro-1-arylnaphtho[1,2-e][1,3]oxazine-3-one derivatives were synthesized in moderate to high yields using a ­novel, facile, and one-pot condensation of β-naphthol, aromatic ­aldehydes and urea under microwave-assisted and thermal solvent-free conditions.

naphthoxazinone - microwave - solvent-free - naphthol - multi-component

References and Notes

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Typical procedure for the preparation of 1,2-dihydro-1-phenylnaphtho[1,2- e ][1,3]oxazine-3-one (4a) under thermal solvent-free conditions: A mixture of β-naphthol (1 mmol), benzaldehyde (1 mmol), urea (1.5 mmol) and PTSA (0.3 mmol) was finely mixed together. The reaction mixture was placed in a screw-capped vial and heated at 160 °C for 1.5 h. After cooling, the reaction mixture was washed with H₂O and then recrystallized from EtOAc-hexane (1:3) to afford the pure product 4a as a white powder (58%).

<A NAME="RD27006ST-12">12</A>

Typical procedure under microwave-assisted conditions: A mixture of β-naphthol (1 mmol), benzaldehyde (1 mmol) and urea (1.5 mmol) were finely mixed together. The reaction mixture was placed in a screw-capped vial and irradiated for 6 min with a power of 900 W. After cooling, the reaction mixture was washed with H₂O and then recrystallized from EtOAc-hexane (1:3) to afford the pure product 4a (81%); mp 218-220 °C; IR (KBr): 3295, 1730, 1517 cm^-1; ¹H NMR (300 MHz, DMSO-d ₆): δ = 6.19 (d, J = 2.1 Hz, 1 H, CH), 7.24-8.00 (m, 11 H, Ar-H), 8.87 (br s, 1 H, NH); ¹³C NMR (75 MHz, DMSO-d ₆): δ = 54.20, 114.50, 117.32, 123.57, 125.54, 127.42, 127.81, 128.47, 129.08, 129.32, 129.41, 130.68, 130.86, 143.34, 147.85, 149.77; MS (ESI): m/z (%) = 275 (7) [M⁺], 231 (100), 202 (35), 51 (24).

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Selected characterization data: 1,2-Dihydro-1-(4-methylphenyl)naphtho[1,2- e ][1,3]oxazine-3-one (4b): mp 166-16 °C; IR (KBr): 3230, 3139, 1717 cm^-1; ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.21 (s, 3 H, CH₃), 6.13 (d, J = 2.4 Hz, 1 H, CH), 7.10-7.99 (m, 10 H, Ar-H), 8.81 (s, 1 H, NH); ¹³C NMR (75 MHz, DMSO-d ₆): δ = 21.06, 53.98, 114.61, 117.29, 123.56, 125.49, 127.32, 127.76, 129.05, 129.33, 129.89, 130.59, 130.85, 137.78, 140.43, 147.80, 149.81; MS (ESI): m/z (%) = 290 (10) [M⁺ + H], 231 (100), 202 (20).
1,2-Dihydro-1-(4-chlorophenyl)naphtho[1,2- e ][1,3]oxazine-3-one (4f): mp 208-210 °C; IR (KBr): 3224, 3146, 1734 cm^-1; ¹H NMR (300 MHz, DMSO-d ₆): δ = 6.24 (s, 1 H, CH), 7.31-8.01 (m, 10 H, Ar-H), 8.91 (s, 1 H, NH); ¹³C NMR (75 MHz, DMSO-d ₆): δ = 53.42, 114.02, 117.34, 123.50, 125.62, 127.91, 128.06, 129.13, 129.23, 129.37, 129.42, 130.87, 133.06, 142.22, 147.90, 149.61; MS (ESI): m/z (%) = 309 (5) [M⁺], 265 (60), 231 (100), 202 (27), 115 (15).
1-{[2-Hydroxynaphthalen-1-yl](phenyl) methyl} urea (intermediate 5): mp 190-192 °C; IR (KBr): 3463, 3406, 3347, 3219, 1664 cm^-1; ¹H NMR (300 MHz, CD₃SOCD₃): δ = 5.82 (s, 2 H, NH₂, exchanges with D₂O), 6.91-7.81 (m, 13 H), 9.94 (br s, 1 H, OH); ¹³C NMR (75 MHz, CD₃SOCD₃): δ = 48.56, 119.05, 120.58, 122.72, 123.27, 126.22, 126.81, 128.26, 128.69, 129.0, 129.33, 132.71, 144.77, 153.51, 159.01; MS (ESI): m/z (%): 275 (5) [M⁺ - NH₃], 231 (100), 202 (15), 144 (100).