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A. Al-Etaibi et al. / Tetrahedron 67 (2011) 6259e6274
134.7, 134.3, 132.7, 130.7, 129.9, 129.4, 129.2, 128.7, 128.6, 128.4,
127.9, 61.8, 52.2. 1H NMR (400 MHz, DMSO-d6):
8.21 (s, 1H, NH,
128.4, 61.0, 52.1. HRMS¼460.0754 (C24H1735ClN4O2S requires
d
460.0755).
exchangeable), 8.14e8.12 (m, 2H), 8.07 (d, 2H, J 7.2), 7.73 (t, 1H, J
7.2), 7.60 (t, 4H, J 8.0), 7.50e7.49 (m, 3H), 7.40 (t, 2H, J 7.2), 7.34 (t,
1H, J 7.2), 6.30 (d, 1H, J 5.4), 5.21 (br d, 1H). 13C NMR (100 MHz,
4.5.9. trans-7-p-Chlorophenyl-8-p-methoxybenzoyl-3-phenyl-7,8-
dihydro-6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-one
8h. Colorless crystals, yield 0.4 g (82%), mp 255e256 ꢀC. MS: m/
z¼490 (Mþ, 100%), 492 (Mþ2, 41%). IR: 3232, 1663, 1598, 1571, 1513,
1463, 1418, 1319, 1296, 1261, 1223, 1171, 1111, 1013, 978, 827, 729. 1H
DMSO-d6):
d 193.4, 152.1, 150.0, 148.0, 136.4, 134.8, 134.4, 133.2,
131.6, 130.5, 129.6, 129.2, 129.1, 128.6, 128.5, 127.7, 58.4, 51.6.
HRMS¼426.1144 (C24H18N4O2S requires 426.1144).
NMR (600 MHz, CDCl3):
d 8.31e8.30 (m, 2H), 7.84 (d, 2H, J 7.2),
7.51e7.48 (m, 6H), 7.39 (d, 2H, J 8.4), 6.97 (d, 2H, J 9.0), 5.43 (d, 1H, J
4.5.4. trans-8-Benzoyl-3-p-methoxyphenyl-7-phenyl-7,8-dihydro-
6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-one 8b. Colorlessþcrys-
tals, yield 0.14 g (31%), mp 239e240 ꢀC. MS: m/z¼456 (M ). IR:
3208, 2916, 2846, 1671, 1598, 1509, 1454, 1325, 1300, 1261, 1222,
9.0), 4.83 (d, 1H, J 9.0), 3.90 (s, 3H). 13C NMR (150 MHz, CDCl3):
d
189.4, 165.0, 151.3, 150.8, 147.9, 135.9, 134.2, 132.6, 131.1, 130.7,
129.6, 129.3, 128.7, 128.4, 127.1, 114.5, 61.0, 55.7, 51.8.
HRMS¼490.0860 (C25H1935ClN4O3S requires 490.0860).
1178, 1109, 1022, 972, 849, 551. 1H NMR (400 MHz, CDCl3):
d 8.34 (d,
2H, J 8.8), 7.84 (d, 2H, J 8.0), 7.62 (t, 1H, J 7.6), 7.54 (dd, 2H, J 8.0, 2.0),
7.49e7.47 (m, 3H), 7.42e7.37 (m, 3H), 6.98 (d, 2H, J 8.8), 5.52 (d,1H, J
8.8), 4.83 (d, 1H, J 8.8), 3.87 (s, 3H, OCH3). 13C NMR (100 MHz,
4.5.10. trans-8-Benzoyl-7-p-methoxyphenyl-3-methyl-7,8-dihydro-
6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-one 8i. Pale yellow crys-
tals, yield 0.21 g (54%), mp 201e202 ꢀC. MS: m/z¼394 (Mþ). IR:
3247, 3062, 3004, 2959, 2838, 1674, 1608, 1514, 1466, 1377, 1306,
1254, 1213, 1180, 1113, 1031, 910, 837, 814, 731. 1H NMR (600 MHz,
CDCl3):
d 191.4, 161.7, 150.4, 150.3, 148.0, 135.8, 134.7, 134.3, 130.4,
129.8, 129.4, 129.2, 128.6, 127.9, 125.2, 113.8, 61.9, 55.4, 52.2.
HRMS¼456.1250 (C25H20N4O3S requires 456.1250).
CDCl3):
d 7.83 (dd, 2H, J 8.4, 1.2), 7.63 (tt, 1H, J 7.2, 1.2), 7.49 (t, 2H, J
7.8), 7.44 (d, 2H, J 9.0), 7.16 (s, 1H, NH), 6.91 (d, 2H, J 9.0), 5.46 (d, 1H,
4.5.5. trans-8-Benzoyl-3-methyl-7-phenyl-7,8-dihydro-6H-[1,2,4]tri-
azino[3,4-b][1,3,4]thiadiazin-4-one 8c. Pale yellow crystals, yield
0.19 g (51%), mp 154e155 ꢀC. MS: m/z¼364 (Mþ). IR: 3251, 1669,
1594, 1529, 1463, 1378, 1303, 1214, 1172, 1111, 967, 807, 739, 692. 1H
J 9.0), 4.75 (d, 1H, J 9.0), 3.68 (s, 3H), 2.65 (s, 3H). 13C NMR (150 MHz,
CDCl3):
d 191.6, 160.5, 154.1, 151.2, 148.7, 134.6, 134.4, 129.2, 129.15,
128.6, 127.5, 114.7, 61.2, 55.3, 51.9, 17.7. HRMS¼394.1094
(C20H18N4O3S requires 394.1094).
NMR (400 MHz, CDCl3):
7.53e7.50 (m, 4H), 7.40e7.37 (m, 3H), 7.21 (s, 1H), 5.48 (d, 1H, J 8.8),
4.79 (d, 1H, J 8.8), 2.52 (s, 3H). 13C NMR (100 MHz, CDCl3):
191.4,
d 7.81 (d, 2H, J 8.8), 7.61 (t, 1H, J 7.2),
4.5.11. trans-7-p-Chlorophenyl-4-oxo-3-phenyl-7,8-dihydro-6H-
[1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carboxylic acid ethyl ester
8k. Colorless crystals from EtOH, yield 0.086 g (20%), mp 227 ꢀC.
MS: m/z¼428 (Mþ, 100%), 430 (Mþ2, 35%). IR: 3232, 2971, 1722,
1677, 1516, 1490, 1470, 1452, 1319, 1187, 1114, 1090, 1034, 864, 689.
d
154.2, 151.2, 148.7, 135.8, 134.6, 134.3, 129.8, 129.4, 129.2, 128.6,
127.9, 61.7, 52.0, 17.7. HRMS¼364.0989 (C19H16N4O2S requires
364.0988).
1H NMR (400 MHz, CDCl3):
d
8.28e8.25 (m, 2H), 7.48e7.43 (m, 8H),
4.59 (d, 1H, J 9.2), 4.53 (d, 1H, J 9.2), 4.23e4.10 (m, 2H), 1.22 (t, 3H, J
7.2). 13C NMR (100 MHz, CDCl3):
167.0, 151.3, 150.8, 147.8, 136.2,
133.4, 132.6, 130.7, 129.7, 129.2, 128.6, 128.4, 62.9, 61.3, 51.3, 13.9. 1H
NMR (400 MHz, DMSO-d6): 8.44 (d, 1H, J 2.4, exchangeable),
4.5.6. trans-8-Benzoyl-3-benzyl-7-p-methoxyphenyl-7,8-dihydro-
6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-one 8d. Colorlessþcrys-
tals, yield 0.26 g (58%), mp 156e157 ꢀC. MS: m/z¼470 (M ). IR:
3241, 3060, 1675, 1608, 1514, 1455, 1309, 1252, 1219, 1176, 1116,
d
d
1028, 977, 835, 816, 721, 689. 1H NMR (400 MHz, CDCl3):
d 7.79 (d,
8.12e8.09 (m, 2H), 7.52e7.46 (m, 7H), 5.30 (d, 1H, J 5.2), 5.15 (dd,
2H, J 7.6), 7.58 (t, 1H, J 7.6), 7.46e7.36 (m, 6H), 7.29 (t, 2H, J 7.2),
7.24e7.22 (m, 1H), 7.13 (s, 1H), 6.83 (d, 2H, J 8.8), 5.44 (d, 1H, J 8.8),
4.67 (d, 1H, J 8.8), 4.16 (s, 2H), 3.74 (s, 3H, OCH3). 13C NMR (100 MHz,
1H, J 5.2, 2.4), 4.19 (q, 2H, J 7.2), 1.19 (t, 3H, J 7.2). 13C NMR (100 MHz,
DMSO-d6):
129.3, 128.8, 128.2, 128.1, 62.3, 57.1, 49.5, 13.9. HRMS¼428.0704
(C20H1735ClN4O3S
requires 428.0704). Anal. Calcd for
d 168.0, 151.6, 149.7, 147.7, 134.6, 133.4, 132.9, 130.1,
CDCl3):
d 191.4, 160.4, 155.3, 151.7, 148.1, 136.1, 134.6, 134.3, 129.4,
129.2, 129.1, 128.6, 128.5, 127.2, 126.9, 114.6, 60.9, 55.3, 51.9, 37.7.
HRMS¼470.1407 (C26H22N4O3S requires 470.1407).
C20H17ClN4O3S: C 56.01; H 4.00; N 13.06; S 7.48. Found: C 56.30; H
4.30; N 12.89; S 7.59.
4.5.7. trans-8-p-Methoxybenzoyl-7-p-methoxyphenyl-3-phenyl-7,8-
dihydro-6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-one
8f. Colorless crystals, yield 0.46 g (94%), mp 242e243 ꢀC. MS: m/
z¼486 (Mþ). IR: 3237, 2933, 2837,1668,1598,1513,1322,1259,1173,
4.5.12. 2-Benzoylmethylsulfanyl-3-benzylideneaminoquinazolin-
4(3H)-one 11. Colorless crystalþs from EtOH, yield 0.36 g (90%), mp
181e182 ꢀC. MS: m/z¼399 (M ). IR: 3060, 2921, 1677, 1605, 1580,
1551, 1469, 1452, 1318, 1291, 1273, 1204, 768, 755, 690. 1H NMR
913, 744. 1H NMR (600 MHz, CDCl3):
d 8.32e8.30 (m, 2H), 7.84 (d,
(400 MHz, CDCl3):
d 9.58 (s, 1H), 8.21 (dd, 1H, J 8.0, 1.2), 8.16e8.13
2H, J 9.0), 7.50e7.44 (m, 6H), 6.95 (d, 2H, J 9.0), 6.91 (d, 2H, J 9.0),
5.48 (d, 1H, J 9.0), 4.78 (d, 1H, J 9.0), 3.89 (s, 3H, OCH3), 3.80 (s, 3H,
(m, 2H), 7.93 (dd, 2H, J 8.4, 1.6), 7.67e7.48 (m, 7H), 7.36 (dt, 1H, J 8.0,
1.2), 7.19 (dd, 1H, J 8.4, 0.8), 4.62 (s, 2H). 13C NMR (100 MHz, CDCl3):
OCH3). 13C NMR (150 MHz, CDCl3):
d 189.8, 164.8, 160.5, 151.7, 150.7,
d
194.5, 162.5, 159.4, 156.9, 146.1, 136.8, 134.5, 133.5, 133.2, 132.3,
147.9, 132.8, 131.1, 130.6, 129.2, 128.6, 128.4, 127.5, 127.4, 114.7, 114.4,
61.2, 55.7, 55.3, 51.8. HRMS¼486.1356 (C26H22N4O4S requires
486.1356).
129.0, 128.9, 128.7, 128.5, 127.3, 126.0, 125.8, 120.3, 38.8.
HRMS¼399.1035 (C23H17N3O2S requires 399.1035).
4.6. Cyclization of 7e,j and 11: general procedure
4.5.8. trans-8-Benzoyl-7-p-chlorophenyl-3-phenyl-7,8-dihydro-
6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-one 8g. Yelþlow crystals,
yield 0.42 g (92%), mp 225e226 ꢀC. MS: m/z¼460 (M , 100%), 462
(Mþ2, 42%). IR: 3241, 1693, 1660, 1595, 1508, 1464, 1328, 1297, 1252,
1182, 1155, 1094, 1063, 932, 789, 767, 690, 662. 1H NMR (400 MHz,
A mixture of each of compounds 7e, j, 11 (1 mmol), triethyl-
amine (1.5 mmol) in ethanol (5 mL) was heated under reflux for
0.5 h. The solvent was then removed in vacuo and the remaining
residue was crystallized from ethanol to give the corresponding
products 8e,j and 12, respectively.
CDCl3):
7.54e7.50 (m, 8H), 7.39 (d, 2H, J 7.2), 5.48 (d, 1H, J 9.0), 4.85 (d, 1H, J
9.0). 13C NMR (100 MHz, CDCl3):
191.1, 151.1, 151.0, 147.9, 136.0,
134.9, 134.2, 134.1, 132.6, 130.7, 129.7, 129.32, 129.3, 128.7, 128.6,
d 8.32e8.30 (m, 2H), 7.86 (d, 2H, J 7.6), 7.67 (t, 1H, J 7.6),
d
4.6.1. trans-8-Benzoyl-7-p-methoxyphenyl-3-phenyl-7,8-dihydro-
6H-[1,2,4]tiazino[3,4-b][1,3,4]thiadiazin-4-one 8e. Yellow crystals,