Coumarin-Based Bioactive Compounds
the synthesized compounds was confirmed by thin layer chromatogra-
phy (TLC) using various solvents of different polarities. Merck silica gel
60 F254 plates were applied for analytical TLC. Melting points were
determined on a Kofler hot stage apparatus and are uncorrected.
Nuclear magnetic resonance spectra were recorded using a Bruker
500 spectrometer (Bruker, Rheinstetten, Germany), and chemical shifts
are expressed as d (ppm) with tetramethylsilane as internal standard.
The IR spectra were obtained on a Nicolet 550-FTIR spectrometer
(potassium bromide disks). Elemental analyses were carried out on a
CHN-O-rapid elemental analyzer (GmbH, Hanau, Germany) for C, H,
and N, and the results are within €0.4% of the theoretical values.
118.5, 118.9, 119.1, 120.2, 124.9, 126.7, 132.5, 137.5, 144.2, 144.4,
147.3, 153.1, 157.5, 163.2, 196.2; Anal. calcd for C17H12O5: C,
68.92; H, 4.08; Found: C, 68.70; H, 4.37.
3-(2-Hydroxy-5-methoxybenzylidene)chroman-
2,4-dione (3d)
Colorless solid (0.88 g, 35%); mp 158–160 ꢀC; IR (KBr,1 ⁄ cm) mmax
3443 (OH), 1703 (C=O); 1H NMR (CDCl3) d 3.99 (s, 3H), 6.88 (t,
J = 7.5 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H),
7.20 (d, J = 7.5 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.53 (m, 2H), 7.94
(s, 1H), 11.72 (bs, 1H, OH); 13C NMR (125 MHz, CDCl3) d 56.3,
115.3, 118.5, 118.9, 119.1, 120.2, 124.9, 126.7, 132.5, 137.5, 144.2,
144.4, 147.3, 153.1, 157.5, 163.2, 196.2; Anal. calcd for C17H12O5:
C, 68.92; H, 4.08; Found: C, 68.73; H, 4.31.
General procedure for synthesis of 3-(2-
hydroxybenzylidene)chroman-2,4-dione
derivatives (3)
A mixture of 4-hydroxycoumarin derivative 2 (10 mmol) and appropri-
ate 2-hydroxybenzaldehyde (12 mmol) in ethanol (15 mL) was refluxed
for 0.5–1 h. The progress of reaction was followed by TLC. After com-
pletion of the reaction, the mixture was allowed to cool and crystals
of corresponding product were formed. Immediately, the precipitated
solid was filtered off and washed with ethanol. If after the cooling of
mixture, appropriate crystals or solid did not form, the solvent was
evaporated under reduced pressure, and the residue was purified by
silica gel column chromatography to give the pure product 3.
7-Hydroxy-3-(2-hydroxybenzylidene)chroman-
2,4-dione (3e)
Yellow solid (0.84 g, 30%); mp 240–242 ꢀC; IR (KBr, 1 ⁄ cm) mmax 3260
(OH), 1685 (C = O); 1H NMR (DMSO-d6) d 6.32 (s, 1H), 6.37 (d,
3
3
3J = 8.8 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H), 7.48 (d, J = 7.5 Hz, 1H),
7.63 (d, 3J = 8.8 Hz, 1H), 7.70 (t, 3J = 7.5 Hz, 1H), 7.82 (d,
3J = 7.5 Hz, 1H), 8.26 (s, 1H), 11.48 (s, 1H, OH); 13C NMR (125 MHz,
DMSO-d6) d 102.9, 109.0, 114.3, 116.7, 118.8, 125.3, 128.4, 129.9,
133.5, 135.0, 142.8, 154.1, 158.5, 163.8, 165.7, 192.4; Anal. calcd for
C16H10O5: C, 68.09; H, 3.57; Found: C, 68.23; H, 3.31.
3-(2-Hydroxybenzylidene)chroman-2,4-dione (3a)
Yellow crystal (0.79 g, 30%); mp 173–175 ꢀC; IR (KBr, 1 ⁄ cm) mmax
3431 (OH), 1721 (C = O); 1H NMR (CDCl3) d 6.89 (td, 3J = 7.5 Hz,
4J = 1.0 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H), 7.38 (td, 3J = 7.5 Hz,
4J = 1.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.54 (m, 2H), 7.60 (dd,
3J = 7.5 Hz, 4J = 1.0 Hz, 1H), 7.67 (td, 3J = 7.5 Hz, 4J = 1.0 Hz,
1H), 7.97 (s, 1H), 11.73 (s, 1H, OH); 13C NMR (125 MHz, CDCl3) d
117.0, 117.9, 118.6, 119.1, 125.1, 126.4, 129.0, 132.5, 133.6, 137.5,
144.2, 154.5, 158.0, 163.2, 195.8. Anal. calcd for C16H10O4: C,
72.18; H, 3.79; Found: C, 72.36; H, 3.97.
6-Fluoro-3-(2-hydroxybenzylidene)chroman-2,4-
dione (3f)
Yellow crystal (0.99 g, 35%); mp 156–158 ꢀC; IR (KBr, 1 ⁄ cm) mmax
1
3
3429 (OH), 1722 (C = O); H NMR (CDCl3) d 7.04 (dd, J = 9.0 Hz,
4J = 4.5 Hz, 1H), 7.23 (dd, 3J = 8.5 Hz, 4J = 3.0 Hz, 1H), 7.28 (dt,
3J = 8.5 Hz, 4J = 3.0 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.44 (d,
J = 7.2 Hz, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.68 (t, J = 7.2 Hz, 1H),
7.99 (s, 1H), 11.53 (s, 1H, OH); 13C NMR (125 MHz, CDCl3) d 116.9,
117.1, 117.7, 120.0, 120.1, 125.2, 125.4, 129.2, 134.0, 144.7, 147.3,
153.8, 155.7, 157.3, 159.4, 195.5; Anal. calcd for C16H9FO4: C,
67.61; H, 3.19; Found: C, 67.28; H, 3.41.
3-(5-Bromo-2-hydroxybenzylidene)chroman-2,4-
dione (3b)
Yellow crystal (1.20 g, 35%); mp 194–196 ꢀC; IR (KBr, 1 ⁄ cm) mmax
3440 (OH), 1721 (C = O); 1H NMR (CDCl3) d 6.89 (td, 3J = 7.5 Hz,
4J = 1.0 Hz, 1H), 7.06 (dd, 3J = 8.5 Hz, 4J = 1.0 Hz, 1H), 7.30 (d,
J = 8.5 Hz, 1H), 7.50 (dd, 3J = 8.0 Hz, 4J = 2.0 Hz, 1H), 7.55 (td,
6-Fluoro-3-(2-hydroxy-3-
methoxybenzylidene)chroman-2,4-dione (3g)
Yellow crystal (0.94 g, 30%); mp 193–195 ꢀC; IR (KBr, 1 ⁄ cm) mmax
4
1
3J = 7.5 Hz, J = 2.0 Hz, 1H), 7.52 (m, 2H), 7.86 (s, 1H), 11.65 (s, 1H,
3417 (OH), 1718 (C = O); H NMR (CDCl3) d 4.02 (s, 3H), 7.05 (m,
OH); 13C NMR (125 MHz, CDCl3) d 117.7, 118.7, 119.2, 119.3, 127.4,
131.1, 132.3, 136.3, 137.7, 142.6, 153.3, 157.3, 163.2, 195.6. Anal.
calcd for C16H9BrO4: C, 55.68; H, 2.63; Found: C, 55.89; H, 2.34.
1H), 7.19 (d, J = 8.0 Hz, 1H), 7.23 (m, 2H), 7.32 (m, 2H), 7.99 (s,
3
1H), 11.49 (s, 1H, OH); 13C NMR (125 MHz, CDCl3) d 56.4, 115.5,
116.9, 117.1, 118.4, 119.9, 120.0, 120.3, 125.1, 125.2, 126.2, 144.9,
147.3, 153.8, 155.7, 157.3, 159.4, 195.5; Anal. calcd for C17H11FO5:
C, 64.97; H, 3.53; Found: C, 65.10; H, 3.39.
3-(2-Hydroxy-3-methoxybenzylidene)chroman-
2,4-dione (3c)
Colorless solid (0.88 g, 35%); mp 217–219 ꢀC; IR (KBr, 1 ⁄ cm) mmax
3428 (OH), 1723 (C = O); 1H NMR (CDCl3) d 3.99 (s, 3H), 6.88 (t,
J = 7.5 Hz, 1H), 7.05 (d, J = 8.2 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H),
7.20 (d, J = 7.5 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.53 (m, 2H), 7.94
(s, 1H), 11.72 (s, 1H, OH); 13C NMR (125 MHz, CDCl3) d 56.3, 115.3,
General procedure for synthesis of 5-(2-
hydroxyphenyl)-2,3-dihydro-1H-chromeno[4,3-
e][1,4]thiazepin-6(5H)-one derivatives (5)
A mixture of 3-(2-hydroxybenzylidene)chroman-2,4-dione derivatives
3 (0.5 mmol) and 2-aminoethanethiol hydrochloride (1.5 mmol) was
Chem Biol Drug Des 2011; 78: 580–586
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