Month 2012
Isomeric 3‐Isoxadiazolylcoumarins and Their Derivatives
7‐N,N‐Diethylamino‐3‐(3‐phenyl‐1,2,4‐oxadiazol‐5‐yl)-
EXPERIMENTAL
coumarin (5f). This compound was obtained as light‐green fine‐
crystalline powder. Yield 38%, m.p. 205–206°C; 1H NMR
(DMSO‐d6): δ 1.12 (t, 6H, J = 7.2 Hz, 2CH2CH3), 3.47
(q, 4H, J = 6.8 Hz, 2CH2CH3), 6.08 (s, 1H, H‐8), 6.30 (d, 1H,
J = 8.7 Hz, H‐6), 7.24 (d, 1H, J = 8.9 Hz, H‐5), 7.55 (m,
3H), 8.07 (m, 2H), 8.82 (s, 1H, H‐4). Anal. Calcd. for
C21H19N3O3: C, 69.79; H, 5.30; N, 11.63. Found: C, 69.83; H,
5.43; N, 11.88.
Melting points were measured with a Buchi B‐520 melting
point apparatus. NMR spectra were recorded on a Varian
Mercury 400 spectrometer in DMSO‐d6 and CDCl3 using
TMS as an internal standard (chemical shifts in ppm). Mass
spectral analysis was performed on a PE SCIEX API 150EX
mass spectrometer. IR spectra were recorded on Tensor 27
spectrometer in KBr. UV spectra were recorded on a “Specord
M40” spectrometer in ethanol.
General procedure for the preparation of 3‐(3‐aryl‐1,2,4‐
oxadiazol‐5‐yl)coumarins, 5a–l: Method A. A mixture of an
appropriate coumarin‐3‐carboxylic acid 3 (10 mmol) and CDI
(0.16 g, 10 mmol) in dry N,N‐dimethylformamide (2 mL) was
kept at 70–80°C for 20 min. Then corresponding amidoxime 4
(11 mmol) was added to a reaction mixture and temperature
was raised up to 110°C. At this temperature, solution was kept
for 3 h. Then solution was cooled, and the formed precipitate
of compound 5 was washed with isopropanol (2 × 5 mL). An
additional purification of compound 5 was performed by crys-
tallization from N,N‐dimethylformamide–isopropanol solvent
system at a suitable ratio.
3‐[3‐(4‐Methoxyphenyl)‐1,2,4‐oxadiazol‐5‐yl]coumarin (5g).
This compound was obtained as white fine‐crystalline powder.
Yield 72%, m.p. 207°C; IR: 1748, 1612, 1588, 1572, 1424,
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1264 cm−1; H NMR (DMSO‐d6): δ 3.85 (s, 3H, OCH3), 7.13
(d, 2H, J = 8.1 Hz), 7.45 (t, 1H, J = 7.3 Hz, H‐6), 7.55
(d, 1H, J = 7.6 Hz, H‐8), 7.84 (t, 1H, J = 7.4 Hz, H‐7), 8.01
(d, 3H, J = 8.1 Hz, H‐5 + Ar‐H), 9.30 (s, 1H, H‐4); ms (m/z)
321(M+), 199, 150, 135. Anal. Calcd. for C18H12N2O4:
C, 67.50; H, 3.78; N, 8.75. Found: C, 67.64; H, 3.87; N, 8.97.
5,6‐Benzo‐3‐[3‐(4‐methoxyphenyl)‐1,2,4‐oxadiazol‐5‐yl]-
coumarin (5h). This compound was obtained as yellow fine‐
crystalline powder. Yield 62%, m.p. 198°C; IR: 1772, 1624, 1608,
1584, 1548, 1476, 1264 cm−1; 1H NMR (DMSO‐d6): δ 3.86
(s, 3H, OCH3), 7.12 (d, 2H, J = 9.3 Hz), 7.63 (d, 1H, J = 8.7 Hz),
7.68 (t, 1H, J = 6.1 Hz), 7.80 (t, 1H, J = 7.2 Hz), 8.05 (d, 2H,
J = 9.3 Hz), 8.08 (d, 1H, J = 7.1 Hz), 8.36 (d, 1H, J = 9.8 Hz),
8.69 (d, 1H, J = 8.7 Hz), 9.67 (s, 1H, H‐4). Anal. Calcd. for
C22H14N2O4: C, 71.35; H, 3.81; N, 7.56. Found: C, 71.51; H,
3.98; N, 7.47.
3‐(3‐Phenyl‐1,2,4‐oxadiazol‐5‐yl)coumarin (5a). This com-
pound was obtained as white fine‐crystalline powder. Yield
45%, m.p. 170–171°C; IR: 1756, 1700, 1608, 1580, 1444,
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1388, 1360, 1224 cm−1; H NMR: δ 7.46 (dt, 1H, J = 6.9 Hz,
J = 1.2 Hz, H‐6), 7.52 (d, 1H, J = 8.0 Hz, H‐8), 7.61 (m,
3H), 7.80 (dt, 1H, J = 8.2 Hz, J = 1.3 Hz, H‐7), 8.04 (dd,
1H, J = 8.1 Hz, J = 1.6 Hz, H‐5), 8.50 (m, 2H), 9.18 (s, 1H,
H‐4). Anal. Calcd. for C17H10N2O3: C, 70.34; H, 3.47; N,
9.65. Found: C, 70.39; H, 3.27; N, 9.67.
6‐Bromo‐3‐[3‐(4‐methoxyphenyl)‐1,2,4‐oxadiazol‐5‐yl]-
coumarin (5i). This compound was obtained as white cotton‐like
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solid. Yield 65%, m.p. 262–264°C; H NMR (DMSO‐d6): δ 3.84
5,6‐Benzo‐3‐(3‐phenyl‐1,2,4‐oxadiazol‐5‐yl)coumarin (5b).
This compound was obtained as yellow fine‐crystalline pow-
der. Yield 55%, m.p. 226–228°C; IR: 1744. 1564, 1552, 1444,
(s, 3H, OCH3), 7.14 (d, 2H, J = 9.4 Hz), 7.48 (d, 1H,
J = 9.3 Hz, H‐8), 7.92 (dd, 1H, J = 9.0 Hz, J = 2.5 Hz, H‐7),
8.00 (d, 2H, J = 9.4 Hz), 8.28 (d, 1H, J = 2.3 Hz, H‐5), 9.08
(s, 1H, H‐4). Anal. Calcd. for C18H11BrN2O4: C, 54.16; H,
2.78; N, 7.02. Found: C, 54.34; H, 2.99; N, 6.87.
7‐Methoxy‐3‐[3‐(4‐methoxyphenyl)‐1,2,4‐oxadiazol‐5‐yl]-
coumarin (5j). This compound was obtained as yellow fine‐
crystalline powder. Yield 68%, m.p. 221–222°C; IR: 1744, 1602,
1568, 1372, 1284, 1260 cm−1; 1H NMR (DMSO‐d6): δ 3.81
(s, 3H, OCH3), 3.90 (s, 3H, OCH3), 7.12 (d, 2H, J = 9.0 Hz),
7.12 (m, 2H, H‐6,8), 7.94 (d, 1H, J = 9.0 Hz, H‐5), 8.00
(d, 2H, J = 9.7 Hz), 9.15 (s, 1H, H‐4). Anal. Calcd. for
C19H14N2O5: C, 65.14; H, 4.03; N, 8.00. Found: C, 65.35;
H, 4.13; N, 8.13.
1400, 1368, 1340, 1224 cm−1 1H NMR (DMSO‐d6): δ 7.63
;
(m, 5H), 7.81 (t, 1H, J = 6.9 Hz), 8.14 (m, 3H), 8.38 (d, 1H,
J = 8.3 Hz), 8.70 (d, 1H, J = 8.3 Hz), 9.69 (s, 1H, H‐4).
Anal. Calcd. for C21H12N2O3: C, 74.11; H, 3.55; N, 8.23.
Found: C, 74.23; H, 3.63; N, 8.41.
6‐Bromo‐3‐(3‐phenyl‐1,2,4‐oxadiazol‐5‐yl)coumarin (5c). This
compound was obtained as yellow fine‐crystalline powder.
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Yield 40%, m.p. 222°C; H NMR (DMSO‐d6): δ 7.46 (d, 1H,
J = 9.5 Hz, H‐8), 7.60 (m, 3H), 7.91 (dd, 1H, J = 8.7 Hz,
J= 2.6 Hz, H‐7), 8.06 (m, 2H), 8.26 (d, 1H, J = 2.1 Hz,
H‐5), 9.15 (s, 1H, H‐4). Anal. Calcd. for C17H9BrN2O3:
C, 55.31; H, 2.46; N, 7.59. Found: C, 55.33; H, 2.39; N, 7.76.
7‐Methoxy‐3‐[3‐phenyl‐1,2,4‐oxadiazol‐5‐yl]coumarin (5d).
This compound was obtained as yellow fine‐crystalline pow-
der. Yield 59%, m.p. 207–208°C; IR: 1752, 1732, 1600, 1560,
8‐Methoxy‐3‐[3‐(4‐methoxyphenyl)‐1,2,4‐oxadiazol‐5‐yl]-
coumarin (5k).
This compound was obtained as pale yellow
fine‐crystalline powder. Yield 53%, m.p. 224–225°C; IR: 1752,
1608, 1576, 1468, 1440, 1428, 1356, 1292 cm−1; 1H NMR
(DMSO‐d6): δ 3.84 (s, 3H, OCH3), 3.98 (s, 3H, OCH3), 7.15
(d, 2H, J = 9.5 Hz), 7.39 (t, 1H, J = 7.7 Hz, H‐6), 7.48 (dd,
1H, J = 9.2 Hz, J = 1.5 Hz, H‐7), 7.57 (dd, 1H, J = 7.3 Hz,
J = 1.8 Hz, H‐5), 8.02 (d, 2H, J = 9.5 Hz), 9.12 (s, 1H, H‐4).
Anal. Calcd. for C19H14N2O5: C, 65.14; H, 4.03; N, 8.00.
Found: C, 65.25; H, 4.13; N, 7.89.
1368, 1228 cm−1 1H NMR (DMSO‐d6): δ 3.90 (s, 3H,
;
OCH3), 7.08 (d, 1H, J = 9.4 Hz, H‐6), 7.08 (s, 1H, H‐8), 7.59
(m, 3H), 7.91 (d, 1H, J = 8.8 Hz, H‐5), 8.08 (m, 2H), 9.05 (s,
1H, H‐4). Anal. Calcd. for C18H12N2O4: C, 67.50; H, 3.78;
N, 8.75. Found: C, 67.43; H, 3.99; N, 8.78.
8‐Methoxy‐3‐(3‐phenyl‐1,2,4‐oxadiazol‐5‐yl)coumarin (5e).
This compound was obtained as yellow fine‐crystalline pow-
der. Yield 60%, m.p. 224–225°C; IR: 1760, 1608, 1576, 1468,
7‐N,N‐Diethylamino‐3‐[3‐(4‐methoxyphenyl)‐1,2,4‐oxadiazol‐
5‐yl]coumarin (5l). This compound was obtained as yellow
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1444, 1356, 1252 cm−1; H NMR (DMSO‐d6): δ 3.92 (s, 3H,
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fine‐crystalline powder. Yield 43%, m.p. 218–219°C; H NMR
OCH3), 7.40 (d, 1H, J = 8.0 Hz), 7.41 (t, 1H, J = 8.1 Hz,
H‐6), 7.60 (m, 4H), 8.08 (m, 2H), 9.02 (s, 1H, H‐4). Anal.
Calcd for C18H12N2O4: C, 67.50; H, 3.78; N, 8.75. Found: C,
67.64; H, 3.62; N, 8.56.
(DMSO‐d6): δ 1.14 (t, 6H, J = 8.4 Hz, 2CH2CH3), 3.49
(q, 4H, J = 6.7 Hz, 2CH2CH3), 3.83 (s, 3H, OCH3), 6.60
(s, 1H, H‐8), 6.83 (dd, 1H, J = 10.1 Hz, J = 2.5 Hz, H‐6),
7.11 (d, 2H, J = 11.7 Hz), 7.74 (d, 1H, J = 10.0 Hz, H‐5),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet