July 2010
2-Bromo-1-(1-alkyl-1H-benzo[d]imidazol-2-yl)-1-ethanone (7) To a
solution of 1-(1-alkyl-1H-benzo[d]imidazol-2-yl)-1-ethanones 6 (0.01 mol)
in acetic acid (15 ml) at reflux, drop wise added a solution of bromine
(0.01 mol) in acetic acid. Then the reaction mixture was maintained under
similar conditions for 3 h with constant stirring. After completion of the re-
action, the mixture was cooled into room temperature, poured into ice cold
water and washed with aq. Sodium bicarbonate solution, dried and recrystal-
lized from ethanol.
955
(1H, d, Jϭ7.6 Hz), 3.84 (3H, s), 2.56 (3H, s), 2.43 (3H, s). MS m/z: 189
(Mϩϩ1).
1-(1-Benzyl-5-methyl-1H-benzo[d]imidazol-2-yl)-1-ethanone (6b): Or-
ange solid, yield 78%, mp 92—94 °C. IR (KBr) cmϪ1: 3045, 2974, 2922,
1707, 1636, 1625. 1H-NMR (CDCl3) d: 7.39 (1H, s), 7.37 (2H, d,
Jϭ7.2 Hz), 7.31 (1H, d, Jϭ7.8 Hz), 7.29 (2H, dd, Jϭ7.4 Hz), 7.27 (1H, d,
Jϭ7.2 Hz), 7.12 (1H, dd, Jϭ8.0 Hz), 5.62 (2H, s), 2.56 (3H, s), 2.43 (3H, s).
MS m/z: 265 (Mϩϩ1).
4-(1H-Benz[d]imidazol-2yl)-3-alkyl-2,3-dihydro-1,3-thiazol-2-amines
1-(5-Chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-1-ethanone (6c): Or-
ange solid, yield 84%, mp 124—126 °C. IR (KBr) cmϪ1: 3064, 2975, 2921,
1714, 1635, 1616, 762. 1H-NMR (CDCl3) d: 7.52 (1H, s), 7.23 (1H, d,
Jϭ6.8 Hz), 7.22 (1H, d, Jϭ7.2 Hz), 3.84 (3H, s), 2.56 (3H, s). MS m/z: 209
(Mϩϩ1).
1-(1-Benzyl-5-chloro-1H-benzo[d]imidazol-2-yl)-1-ethanone (6d): Brown
solid, yield 81%, mp 70—72 °C. IR (KBr) cmϪ1: 3054, 2982, 2919, 1712,
1642, 1632, 754. 1H-NMR (CDCl3) d: 7.54 (1H, s), 7.40 (2H, d, Jϭ7.6 Hz),
7.29 (2H, dd, Jϭ7.4 Hz), 7.12 (1H, dd, Jϭ8.0 Hz), 7.25 (2H, d, Jϭ7.8 Hz),
5.62 (2H, s), 2.56 (3H, s). MS m/z: 285 (Mϩϩ1).
(8) To
a solution of 2-bromo-1-(1-alkyl-1H-benzo[d]imidazol-2-yl)-1-
ethanone 7 (0.01 mol) in dimethylformamide (DMF) (20 ml) was added the
solution of thiourea (0.01 mol) in DMF (15 ml). The reaction mixture was
then stirred at room temperature for 2 h. When the reaction was completed
(monitored by TLC), the reaction mixture was poured into ice cold water to
separate the product in solid form, dried and recrystallized from ethanol.
1-(1H-Benzo[d]imidazol-2-yl)-1-ethanol (3a): Yellow solid, yield 90%,
1
mp 180—182 °C. IR (KBr) cmϪ1: 2971, 1623, 1458, 1215, 1103. H-NMR
(CDCl3) d: 10.30 (1H, br s), 7.52 (2H, d, Jϭ7.8 Hz), 7.32 (2H, d, Jϭ1.9 Hz),
4.8 (1H, s), 3.05 (1H, q, Jϭ7.4 Hz), 1.62 (3H, d, Jϭ7.2 Hz). MS m/z: 163
(Mϩϩ1).
2-Bromo-1-(1,5-dimethyl-1H-benzo[d]imidazol-2-yl)-1-ethanone
(7a):
Yellow solid, yield 77%, mp 106—106 °C. IR (KBr) cmϪ1: 3045, 2975,
2921, 1708, 1632, 1641, 545. 1H-NMR (CDCl3) d: 7.65 (1H, s), 7.56 (1H, d,
Jϭ8.0 Hz), 7.38 (1H, d, Jϭ8.2 Hz), 4.27 (2H, s), 3.76 (3H, s), 2.43 (3H, s).
MS m/z: 268 (Mϩϩ1).
1-(5-Methyl-1H-benzo[d]imidazol-2-yl)-1-ethanol (3b): Dark yellow
solid, yield 90%, mp 160—162 °C. IR (KBr) cmϪ1: 3038, 2701, 1629, 1449,
1
1316, 1101. H-NMR (CDCl3) d: 11.61 (1H, br s), 7.32 (2H, d, Jϭ8.0 Hz),
7.24 (1H, d, Jϭ1.9 Hz), 4.85 (1H, s), 3.05 (1H, q, Jϭ7.8 Hz), 2.30 (3H, s),
1-(1-Benzyl-5-methyl-1H-benzo[d]imidazol-2-yl)-2-bromo-1-ethanone
1.52 (3H, d, Jϭ7.4 Hz). MS m/z: 177 (Mϩϩ1).
(7b): Pale brown solid, yield 84%, mp 65—67 °C. IR (KBr) cmϪ1: 3055,
1
1-(5-Chloro-1H-benzo[d]imidazol-2-yl)-1-ethanol (3c): Brown solid,
yield 65%, mp 171—173 °C. IR (KBr) cmϪ1: 2981, 1623, 1444, 1210, 1082.
1H-NMR (CDCl3) d: 12.50 (1H, s), 7.55 (2H, d, Jϭ7.2 Hz), 7.20 (1H, d,
Jϭ2.1 Hz), 4.91 (1H, s), 3.10 (1H, q, Jϭ7.8 Hz), 1.56 (3H, d, Jϭ7.2 Hz).
MS m/z: 197 (Mϩϩ1).
2964, 2923, 1707, 1623, 1635, 561. H-NMR (CDCl3) d: 7.67 (1H, s), 7.62
(2H, d, Jϭ8.0 Hz), 7.58 (1H, d, Jϭ7.8 Hz), 7.40 (1H, d, Jϭ7.8 Hz), 7.24
(2H, dd, Jϭ7.6 Hz), 7.12 (1H, dd, Jϭ7.4 Hz), 5.58 (2H, s), 4.27 (2H, s), 2.43
(3H, s). MS m/z: 344 (Mϩϩ1).
2-Bromo-1-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-1-ethanone
(7c): Brown-yellow solid, yield 65%, mp 78—80 °C. IR (KBr) cmϪ1: 3062,
1-(5-Nitro-1H-benzo[d]imidazol-2-yl)-1-ethanol (3d): Brown solid, yield
75%, mp 148—150 °C. IR (KBr) cmϪ1: 3342, 3215, 3024, 2865, 2240,
1
2973, 2926, 1710, 1624, 1638, 714, 568. H-NMR (CDCl3) d: 7.80 (1H, s),
1
1420, 1248. H-NMR (CDCl3) d: 10.63 (1H, br s) 7.91 (1H, d, Jϭ1.9 Hz),
7.46 (1H, d, Jϭ7.6 Hz), 7.32 (1H, d, Jϭ7.4 Hz), 4.27 (2H, s), 3.76 (3H, s).
MS m/z: 288 (Mϩϩ1).
7.76 (2H, d, Jϭ7.4 Hz), 5.16 (1H, s), 3.06 (1H, q, Jϭ7.5 Hz), 1.64 (3H, d,
Jϭ7.5 Hz). MS m/z: 208 (Mϩϩ1).
1-(1-Benzyl-5-chloro-1H-benzo[d]imidazol-2-yl)-2-bromo-1-ethanone
(7d): Pale yellow solid, yield 65%, mp 78—80 °C. IR (KBr) cmϪ1: 3068,
1-(1H-Benzo[d]imidazol-2-yl)-1-ethanone (4a): Yellow solid, yield 78%,
mp 189—191 °C. IR (KBr) cmϪ1: 3289, 3059, 3015, 1674, 1580, 1445,
1235, 1147. 1H-NMR (CDCl3) d: 13.02 (1H, s), 7.85 (1H, d, Jϭ7.8 Hz),
7.52 (1H, d, Jϭ7.6 Hz), 7.32 (2H, t, Jϭ7.4 Hz), 2.74 (3H, s). MS m/z: 161
(Mϩϩ1).
1
2973, 2928, 1708, 1632, 1614, 710, 556. H-NMR (CDCl3) d: 7.83 (1H, s),
7.62 (2H, d, Jϭ7.8 Hz), 7.49 (1H, d, Jϭ7.6 Hz), 7.43 (1H, d, Jϭ8.0 Hz),
7.24 (2H, dd, Jϭ7.8 Hz), 7.12 (1H, dd, Jϭ7.6 Hz), 5.58 (2H, s), 4.27 (2H, s).
MS m/z: 364 (Mϩϩ1).
1-(5-Methyl-1H-benzo[d]imidazol-2-yl)-1-ethanone (4b): Yellow solid,
4-(1,5-Dimethyl-1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amine (8a): Yel-
low solid, yield 74%, mp 130—132 °C. IR (KBr) cmϪ1: 3184, 3027, 1603,
1555, 1523, 1496. 1H-NMR (CDCl3) d: 7.36 (1H, s), 7.20 (1H, d,
Jϭ7.4 Hz), 7.16 (1H, s), 7.08 (1H, d, Jϭ7.8 Hz), 5.02 (2H, s), 3.70 (3H, s),
2.43 (3H, s). MS m/z: 245 (Mϩϩ1).
4-(1-Benzyl-5-methyl-1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amine (8b):
Colorless solid, yield 774%, mp 132—134 °C. IR (KBr) cmϪ1: 3178, 3032,
1612, 1565, 1527, 1487. 1H-NMR (CDCl3) d: 7.38 (1H, s), 7.33 (2H, d,
Jϭ7.6 Hz), 7.22 (2H, d, Jϭ7.4 Hz), 7.17 (2H, dd, Jϭ7.8 Hz), 7.12 (1H, dd,
Jϭ8.0 Hz), 7.10 (1H, s), 5.26 (2H, s), 5.02 (2H, s), 2.43 (3H, s). MS m/z:
321 (Mϩϩ1).
4-(5-Chloro-1-methyl-1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amine (8c):
Yellow solid, yield 70%, mp 120—122 °C. IR (KBr) cmϪ1: 3166, 3032,
1610, 1565, 1532, 1486, 745. 1H-NMR (CDCl3) d: 7.50 (1H, s), 7.31 (1H, d,
Jϭ7.8 Hz), 7.18 (1H, d, Jϭ7.6 Hz), 7.16 (1H, s), 5.02 (2H, s), 3.70 (3H, s).
MS m/z: 245 (Mϩϩ1).
1
yield 80%, mp 170—172 °C. IR (KBr) cmϪ1: 3365, 2919, 2852, 1693. H-
NMR (CDCl3) d: 11.23 (1H, s), 7.65 (1H, d, Jϭ8.0 Hz), 7.48 (1H, d,
Jϭ7.8 Hz), 7.24 (1H, s), 3.42 (3H, s), 2.45 (3H, s). MS m/z: 174 (Mϩϩ1).
1-(5-Chloro-1H-benzo[d]imidazol-2-yl)-1-ethanone (4c): Yellow solid,
yield 65%, mp 185—187 °C. IR (KBr) cmϪ1: 3294, 3066, 3021, 1677, 1574,
1335, 1219, 1060. 1H-NMR (CDCl3) d: 13.02 (1H, s), 7.52 (2H, d,
Jϭ7.4 Hz), 7.32 (1H, s), 2.74 (3H, s). MS m/z: 195 (Mϩϩ1).
1-(5-Nitro-1H-benzo[d]imidazol-2-yl)-1-ethanone (4d): Pale yellow solid,
yield 70%, mp 155—157 °C. IR (KBr) cmϪ1: 3360, 3040, 2865, 2160, 1720,
1356, 1240. 1H-NMR (CDCl3) d: 8.91 (1H, s), 8.77 (1H, s), 8.13 (1H, d,
Jϭ7.2 Hz), 8.09 (1H, d, Jϭ7.4 Hz), 2.79 (3H, s). MS m/z: 206 (Mϩϩ1).
4-(1H-Benz[d]imidazol-2yl)-1,3-thiazol-2-amine (5a): Colorless solid,
yield 62%, mp 109—111 °C. IR (KBr) cmϪ1: 3285, 3240, 3045, 2990, 1605,
1596, 780. 1H-NMR (CDCl3) d: 7.41 (2H, dd, Jϭ7.4 Hz), 7.73 (2H, d,
Jϭ7.8 Hz), 7.51 (1H, s), 6.31 (3H, s). MS m/z: 217 (Mϩϩ1).
4-(5-Methyl-1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amine (5b): Yellow
4-(1-Benzyl-5-chloro-1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amine (8d):
Yellow solid, yield 65%, mp 116—118 °C. IR (KBr) cmϪ1: 3174, 3038,
1618, 1574, 1544, 1474, 754. 1H-NMR (CDCl3) d: 7.52 (1H, s), 7.33 (3H, d,
Jϭ7.6 Hz), 7.21 (1H, d, Jϭ7.8 Hz), 7.19 (2H, dd, Jϭ7.4 Hz), 7.12 (1H, dd,
Jϭ8.0 Hz), 7.10 (1H, s), 5.26 (2H, s), 5.02 (2H, s). MS m/z: 341 (Mϩϩ1).
solid, yield 68%, mp 146—148 °C. IR (KBr) cmϪ1: 3356, 3145, 2872, 2174,
1
1735, 1362, 1254. H-NMR (CDCl3) d: 7.39 (1H, d, Jϭ7.6 Hz), 7.39 (1H,
s), 7.11 (1H, d, Jϭ8.0 Hz), 7.51 (1H, s), 6.31 (3H, s), 2.43 (3H, s). MS m/z:
231 (Mϩϩ1).
4-(5-Chloro-1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amine (5c): Brown
solid, yield 66%, mp 136—138 °C. IR (KBr) cmϪ1: 3266, 3254, 3038, 2982,
References
1
1614, 1565, 875. H-NMR (CDCl3) d: 7.76 (1H, d, Jϭ7.1 Hz), 7.69 (1H, d,
1) Porcari A. R., Devivar R. V., Kucera L. S., Drach J. C., Townsend L.
B., J. Med. Chem., 41, 1252—1262 (1998).
Jϭ7.2 Hz), 7.64 (1H, s), 7.42 (1H, s), 7.15 (1H, s), 6.31 (2H, s). MS m/z:
251 (Mϩϩ1).
2) Roth Y., Morningstar M. L., Boyer P. L., Hughes S. H., Buckheitjr R.
W., Michejda C. J., J. Med. Chem., 40, 4199—4207 (1997).
3) Migawa M. T., Girardet J. L., Walker J. A., Koszalka G. W., Chamber-
lain S. D., Drach J. C., Townsend L. B., J. Med. Chem., 41, 1242—
1251 (1998).
4) Tamm I., Sehgal P. B., Adv. Virus Res., 22, 187—258 (1978).
5) Tamm I., Science, 126, 1235—1236 (1957).
6) Czarny A., Wilson W. D., Boykin D. W., J. Heterocycl. Chem., 33,
1393—1397 (1996).
4-(5-Nitro-1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amine (5d): Orange
solid, yield 71%, mp 142—144 °C. IR (KBr) cmϪ1: 3274, 3258, 3043, 2982,
1647, 1552, 1023, 845. 1H-NMR (CDCl3) d: 8.62 (1H, s), 8.01 (1H, d,
Jϭ8.2 Hz), 7.87 (1H, d, Jϭ7.6 Hz), 7.51 (1H, s), 6.31 (3H, s). MS m/z: 262
(Mϩϩ1).
1-(1,5-Dimethyl-1H-benzo[d]imidazol-2-yl)-1-ethanone (6a): Yellow
solid, yield 80%, mp 70—72 °C. IR (KBr) cmϪ1: 3030, 2965, 2910, 1702,
1640, 1605. 1H-NMR (CDCl3) d: 7.36 (1H, s), 7.29 (1H, d, Jϭ7.4 Hz), 7.25