S.B. Ferreira et al. / European Journal of Medicinal Chemistry 46 (2011) 3071e3077
3075
J ¼ 1.2 and 7.8 Hz, H-10), 8.01 (1H, dd, J ¼ 1.9 and 8.0 Hz, H-7). 13
C
6.2 Hz, OCH2CH3), 2.15 (1H, dddd, J ¼ 2.1, 3.7, 6.1 and 12.5 Hz, H-3a),
2.22 (1H, dddd, J ¼ 3.5, 6.5, 7.3 and 12.5 Hz, H-3b), 2.58 (1H, ddd,
J ¼ 3.7, 6.5 and 9.1 Hz, H-4a), 2.69 (1H, ddd, J ¼ 3.5, 6.1 and 9.1 Hz H-
4b), 4.09 (2H, dd, J ¼ 1.8 and 6.2 Hz, OCH2CH3), 5.11 (1H, dd, J ¼ 2.1
and 7.3 Hz, H-2), 7.05e7.15 (2H, m, H-ar), 7.40e7.47 (2H, m, H-ar),
7.53 (1H, ddd, J ¼ 1.5, 7.7 and 9.2 Hz, H-8), 7.59 (1H, ddd, J ¼ 1.5, 7.7
and 9.2 Hz, H-9), 7.83 (1H, dd, J ¼ 1.2 and 7.7 Hz, H-10), 8.12 (1H, dd,
NMR (CDCl3, 75 MHz):
d 18.2 (C-4), 28.2 (C-3), 79.2 (C-2), 113.8 (C-
4a), 123.8 (C-10), 127.1 (C-7), 128.6 (C-8), 128.8 (C-20), 129.8 (C-6a),
130.7 (C-30), 131.9 (C-90), 134.2 (C-40), 134.8 (C-10), 137.7 (C-10a),
162.5 (10b), 178.3 and 179.2 (C-5 and C-6). HRMS (ESI) calcd for
C21H18O3: 324.0553, Found: 324.8102.
4.2.3. 2-p-tolyl-3,4-Dihydro-2H-benzo[h]chromene-5,6-dione (3)
Compound 3 was obtained as an orange solid, 20% yield,
J ¼ 1.5 e 7.7 Hz, H-7). 13C NMR (CDCl3, 75 MHz):
d 14.4 (CH3), 19.4 (C-
4), 27.0 (C-3), 64.2 (OCH2CH3), 74.5 (C-2), 115.8 (C-4a), 115.0 (C-10),
124.9 (C-7), 125.1 (C-8), 129.2 (C-20), 129.6 (C-6a), 130.2 (C-30), 132.4
(C-90), 131.9 (C-10a), 134.5 (C-10), 160.6 (C-40), 163.1 (C-10b), 179.4
and 180.2 (C-5 and C-6). HRMS (ESI) calcd for C21H18O4: 334.1205,
Found: 334.1502.
m.p. ¼ 165e167 ꢂC. IR (KBr, cmꢁ1):
n 1697, 1647, 1605, 1590, 1572,
1393, 1301, 1280, 1158, 1076, 922, 771; 1H NMR (CDCl3, 300 MHz):
d
2.06 (1H, dddd, J ¼ 2.4, 3.6, 5.6 and 12.7 Hz, H-3a), 2.31 (1H, dddd,
J ¼ 3.1, 6.2, 7.8 and 12.7 Hz, H-3b), 2.40 (3H, s, CH3), 2.59 (1H, ddd,
J ¼ 3.6, 6.2 and 8.7 Hz, H-4a), 2.77 (1H, ddd, J ¼ 3.1, 5.6 and 8.7 Hz,
H-4b), 5.24 (1H, dd, J ¼ 2.4 and 7.8 Hz, H-2), 7.25 (2H, d, J ¼ 7.7 Hz,
H-meta tolyl), 7.32 (2H, d, J ¼ 7.7 Hz, H-ortho tolyl), 7.51 (1H, ddd,
J ¼ 1.4, 7.5 and 8.7 Hz, H-8), 7.62 (1H, ddd, J ¼ 1.4, 7.5 and 9.0 Hz, H-
9), 7.81 (1H, dd, J ¼ 1.2 and 7.8 Hz, H-10), 8.01 (1H, dd, J ¼ 1.4 and
4.2.7. 2-Methyl-2-phenyl-3,4-dihydro-2H-benzo[h]chromene-5,6-
dione (7)
Compound 7 was obtained as an orange solid, 20% yield,
m.p. ¼ 155e157 ꢂC. IR (KBr, cmꢁ1):
n
1606, 1647, 1603, 1387, 1305,
d 1.78 (3H, s, CH3), 2.05 (1H,
7.5 Hz, H-7); 13C NMR (CDCl3, 75 MHz):
d
18.7 (C-4), 21.4 (CH3), 28.6
1359, 919. 1H NMR (CDCl3, 300 MHz):
(C-3), 80.4 (C-2), 114.3 (C-4a), 124.3 (C-10), 126.1 (C-7), 128.9 (C-8),
129.7 (C-20-phenyl), 130.2 (C-6a), 131.0 (C-30-phenyl), 132.4 (C-90),
135.1 (C-10-phenyl), 136.7 (C-40-phenyl), 138.7 (C-10a), 163.2 (C-
10b), 178.8 and 179.8 (C-5 and C-6). HRMS (ESI) calcd for C20H16O3:
304.1099, Found: 304.1012.
ddd, J ¼ 3.1, 5.3 and 12.9 Hz, H-3a), 2.24 (1H, ddd, J ¼ 3.0, 6.0 and
12.9 Hz, H-3b), 2.42 (1H, ddd, J ¼ 3.1, 6.0 and 7.9 Hz, H-4a), 2.60 (1H,
ddd, J ¼ 3.0, 5.3 and 7.9 Hz, H-4b), 7.29e7.38 (5H, m, 2-phenyl), 7.55
(1H, ddd, J ¼ 1.2, 7.5 and 9.0 Hz, H-8), 7.71 (1H, ddd, J ¼ 1.2, 7.5 and
9.0 Hz, H-9), 8.00 (1H, dd, J ¼ 1.0 and 7.5 Hz, H-10), 8.10 (1H, dd,
J ¼ 1.0 and 7.5 Hz, H-7). 13C NMR (CDCl3, 75 MHz):
d 16.5 (C-4), 29.4
4.2.4. 2-(4-Methoxyphenyl)-3,4-dihydro-2H-benzo[h]chromene-
5,6-dione (4)
(CH3), 31.1 (C-3), 82.9 (C-2), 114.2 (C-4a), 124.1 (C-10), 124.2 (C-7),
127.8 (C-40-phenyl), 129.0 (C-8), 129.1 (C-20-phenyl), 131.0 (C-30-
phenyl), 135.2 (C-10-phenyl), 130.3 (C-6a), 132.4 (C-10a), 143.2 (C-9),
161.9 (10b), 178.6 and 179.7 (C-5 and C-6). HRMS (ESI) calcd for
C20H16O3: 304.1099, Found: 304.3501.
Compound 4 was obtained as an orange solid, 17% yield,
m.p. ¼155e157 ꢂC.IR(KBr, cmꢁ1):
n
1605,1572,1525,1280,1249,1170,
2.11 (1H, dddd, J ¼ 2.4, 3.6, 5.7
921, 774; 1H NMR (CDCl3, 300 MHz):
d
and 13.0 Hz, H-3a); 2.31 (1H, dddd, J ¼ 3.2, 6.2, 7.8 and 13.0 Hz, H-3b);
2.61 (1H, ddd, J ¼ 3.6, 6.2 and 8.7 Hz, H-4a), 2.76 (1H, ddd, J ¼ 3.2, 5.7
and 8.7 Hz, H-4b), 3.85 (3H, s, OCH3), 5.20 (1H, dd, J ¼ 2.4 and 7.8 Hz,
C-2), 6.96e6.99 (2H, m, H-ar), 7.34e7.37 (2H, m, H-ar), 7.51 (1H, ddd,
J ¼ 1.4, 7.5 and 8.7 Hz, H-8), 7.60 (1H, ddd, J ¼ 1.4, 7.5 and 9.0 Hz, H-9),
7.80 (1H, dd, J ¼ 1.2 and 7.8 Hz, H-10), 8.08 (1H, dd, J ¼ 1.4 and 7.5 Hz,
4.2.8. 2-(2,4-Dimethylphenyl)-3,4-dihydro-2H-benzo[h]chromene-
5,6-dione (8)
Compound 8 was obtained as an orange solid, 27% yield,
m.p. ¼ 164e167 ꢂC. IR (KBr, cmꢁ1):
n
1694, 1646, 1603, 1574, 1394,
2.07 (1H,
1283, 1231, 1160, 914, 728. 1H NMR (CDCl3, 300 MHz):
d
H-7). 13C NMR (CDCl3, 75 MHz):
d
18.4 (C-4), 28.0 (C-3), 55.2 (OCH3),
dddd, J ¼ 2.4, 2.8, 5.6 and 11.8 Hz, H-3a), 2.31 (1H, dddd, J ¼ 3.7, 6.5,
7.8 and 11.8 Hz, H-3b), 2.36 (3H, s, CH3), 2.38 (3H, s, CH3), 2.63 (1H,
ddd, J ¼ 2.8, 6.5 and 8.0 Hz, H-4a), 2.85 (1H, ddd, J ¼ 3.7, 5.6 and
8.0 Hz, H-4b), 5.35 (1H, dd, J ¼ 2.4 and 7.8 Hz, C-2), 7.08e7.13 (2H,
m, H-ar), 7.33 (1H, d, J ¼ 7.8 Hz, H-ar), 7.51 (1H, ddd, J ¼ 0.9, 7.5 and
8.7 Hz, H-8), 7.61 (1H, ddd, J ¼ 1.4, 7.5 and 9.0 Hz, H-9), 7.71 (1H, dd,
J ¼ 0.9 and 7.8 Hz, H-10), 8.06 (1H, dd, J ¼ 1.4 and 7.5 Hz, H-7). 13C
79.9 (C-2), 113.8 (C-4a), 114.0 (C-10), 123.9 (C-7), 127.2 (C-8), 128.5
(C-20), 129.8 (C-6a), 130.6 (C-30), 131.2 (C-90), 132.0 (C-10a), 134.7
(C-10),159.6 (C-40),162.9(C-10b),178.4and 179.4(C-5 and C-6). HRMS
(ESI) calcd for C21H18O3: 320.1049, Found: 320.3596.
4.2.5. 2-(4-Fluorophenyl)-3,4-dihydro-2H-benzo[h]chromene-5,6-
dione (5)
NMR (CDCl3, 75 MHz): d 19.2 (CH3), 19.2 (C-4), 21.2 (CH3), 27.5 (C-3),
Compound 5 was obtained as an orange solid, 26% yield,
77.9 (C-2),114.2 (C-4a),124.3 (C-10),125.8 (C-7),127.3 (C-40-phenyl),
128.9 (C-8), 130.9 (C-20-phenyl), 131.8 (C-30-phenyl), 134.6 (C-10-
phenyl),130.2 (C-6a),132.4 (C-10a),163.5 (10b),178.7 and 179.8 (C-5
and C-6). HRMS (ESI) calcd for C21H18O3: 318.1256, Found:
318.3792.
m.p. ¼ 142e147 ꢂC. IR (KBr, cmꢁ1):
n
1573, 1607, 1513, 1394, 1280,
2.07 (1H, dddd,
1229, 1156, 922; 1H NMR (CDCl3, 300 MHz):
d
J ¼ 2.4, 3.2, 5.6 and 12.8 Hz, H-3a), 2.34 (1H, dddd, J ¼ 3.1, 6.5, 7.8
and 12.8 Hz, H-3b), 2.61 (1H, ddd, J ¼ 3.2, 6.5 and 8.7 Hz, H-4a), 2.75
(1H, ddd, J ¼ 3.1, 5.6 and 8.7 Hz, H-4b), 5.24 (1H, dd, J ¼ 2.4 and
7.8 Hz, H-2), 7.15 (2H, t, J ¼ 8.5 Hz, 2CHar-F), 7.39e7.44 (2H, m, H-
ar), 7.53 (1H, ddd, J ¼ 1.2, 7.2 and 8.7 Hz, H-8), 7.64 (1H, ddd, J ¼ 1.4,
7.8 and 9.2 Hz, H-9), 7.83 (1H, dd, J ¼ 1.1 and 6.5 Hz, H-10), 8.01 (1H,
4.2.9. 4-(4-Nitrophenyl)-2-p-tolyl-3,4-dihydro-2H-benzo[h]
chromene-5,6-dione (9)
Compound 9 was obtained as an orange solid, 24% yield,
m.p. ¼ 232e235 ꢂC. IR (KBr, cmꢁ1): 1696, 1645, 1600, 1570, 1513,
1344, 1287, 1233, 1168, 1091, 912, 736, 702. 1H NMR (300 MHz,
dd, J ¼ 1.1 and 6.3 Hz, H-7). 13C NMR (CDCl3, 75 MHz):
d 18.3 (C-4),
28.3 (C-3), 79.4 (C-2), 113.8 (C-4a), 115.4 and 115.7 (d, J ¼ 21.4 Hz, C-
30), 123.8 (C-10), 127.5 (C-7), 127.6 (C-8), 128.6 (C-10), 129.8 (C-6a),
130.7 (C-30), 131.8 (C-20), 134.7 (C-90), 135.7 (C-40), 137.7 (C-10a),
162.6 (C-10b), 178.4 and 179.2 (C-5 and C-6). HRMS (ESI) calcd for
C21H18O3: 308.0849, Found: 308.3243.
CDCl3):
d
2.19 (1H, dt, J ¼ 2.4 and 14.4 Hz, H-3a syn isomer) and 2.27
(1H, dt, J ¼ 11.2 and 14.4 Hz, H-3a anti isomer), 2.38 and 2.39 (3H, s,
CH3), 2.55 (1H, ddd, J ¼ 5.9, 12.0 and 14.4 Hz, H-3b syn isomer) and
2.61 (1H, ddd, J ¼ 2.2, 7.1 and 14.4 Hz, H-3b anti isomer), 4.31 (1H,
dd, J ¼ 7.1 and 11.0 Hz, H-4 anti isomer) and 4.48 (1H, dd, J ¼ 2.4 and
5.9 Hz, H-4 syn isomer), 5.07 (1H, dd, J ¼ 2.4 and 12.0 Hz, H-2 syn
isomer) and 5.31 (1H, dd, J ¼ 2.2 and 11.2 Hz, H-2 anti isomer), 7.25
(1H, d, J ¼ 8.1 Hz, H-meta p-tolyl), 7.35 (1H, d, J ¼ 8.1 Hz, H-ortho p-
tolyl), 7.38 and 7.47 (1H, d, J ¼ 8.8 Hz, H-ortho 4-nitrophenyl),
7.56e7.94 (1H, m, H-7), 7.56e7.94 (1H, m, H-8), 8.11 (1H, d,
4.2.6. 2-(4-Ethoxyphenyl)-3,4-dihydro-2H-benzo[h]chromene-5,6-
dione (6)
Compound 6 was obtained as an orange solid, 22% yield,
m.p. ¼ 145e147 ꢂC. IR (KBr, cmꢁ1):
n 1610, 1642, 1601, 1390, 1300,
1365, 939. 1H NMR (CDCl3, 300 MHz): 1.45 (3H, dd, J ¼ 1.8 and