F. Sa˛czewski et al. / Bioorg. Med. Chem. 14 (2006) 6679–6685
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3.5. 2-(4,5-Dihydro-1H-imidazol-2-yl)-5,6-dimethyl-1H-
benzimidazole (5)
1665, 1618, 1587, 1522, 1489, 1436, 1384, 1365, 1346,
1318, 1282, 1269, 1213, 1189, 1146, 1134, 1014.
Yield 66%; mp 242–243 ꢁC (benzene). IR kmax (KBr)
Compound 11 · HCl, yield 70%; mp 282–285 ꢁC
(EtOH). IR kmax (KBr) cmꢁ1: 3419, 2983, 2901, 2714,
2581, 1748, 1603, 1552, 1524, 1508, 1484, 1365, 1317,
1255. H NMR (200 MHz, DMSO–d6) d: 1.41 (s, 6H,
CH3), 4.42 (s, 2H, CH2), 7.47 (m, 2H, aromat), 7.77
(m, 2H, aromat).
cmꢁ1: 3295, 3454, 3045, 2965, 2938, 2898, 1627, 1553,
1
1436, 1378, 1288. H NMR (200 MHz, DMSO–d6) d:
2.30 (s, 6H, CH3), 3.66 (s, 4H, CH2), 7.34 (s, 2H, aro-
1
mat). MS (EI) m/z: 214 (M+).
Compound 5 · HCl, yield 65%; mp 298–301 ꢁC (EtOH).
IR kmax (KBr) cmꢁ1: 3242, 3105, 3066, 2975, 2861, 2779,
1635, 1599, 1441, 1288, 1259, 1180, 1013. 1H NMR
(500 MHz, DMSO–d6) d: 2.36 (s, 6H, CH3), 4.04 (s,
4H, CH2), 7.55 (s, 2H, aromat), 11.06 (bs, 2H, NH),
14.20 (bs, 1H, NH).
3.10. 2-(4,5-Dihydro-1H-imidazol-2-yl)benzothiazole (13)
Yield 20%; mp 147–150 ꢁC (cyclohexane), Ref. 19 151–
152 ꢁC (cyclohexane).
Compound 13 · HCl, yield 75%; mp 264–266 ꢁC
(i-PrOH). IR kmax (KBr) cmꢁ1: 3395, 3213, 3090, 3024,
2923, 2719, 1610, 1586, 1478, 1351, 1285, 1258, 1027.
1H NMR (200 MHz, DMSO–d6) d: 4.08 (s, 4H, CH2),
7.54 (m, 2H, aromat), 8.27 (m, 1H, aromat), 8.44 (m,
1H, aromat), 11.55 (bs, 2H, NH).
3.6. 5,6-Dichloro-2-(4,5-Dihydro-1H-imidazol-2-yl)-1H-
benzimidazole (6)
Yield 87%; mp 285–287 ꢁC (toluene). IR kmax (KBr)
cmꢁ1: 3424, 3082, 2938, 2786, 2606, 1628, 1585, 1382,
1
1322, 1286, 1087. H NMR (200 MHz, DMSO–d6) d:
3.88 (s, 4H, CH2), 7.77 (s, 2H, aromat).
3.11. Preparation of 2,3,5,6-tetrahydrobenzo[4,5]imi-
dazo[1,2-a]imidazo[2,1-c]pyrazine (8)
Compound 6 · HCl, yield 61%; mp 178–181 ꢁC (i-
PrOH). IR kmax (KBr) cmꢁ1: 3405, 3071, 2976, 2897,
2840, 2796, 1643, 1607, 1402, 1317, 1290, 1094. 1H
NMR (200 MHz, DMSO–d6) d: 4.07 (s, 4H, CH2),
8.13 (s, 2H, aromat).
Thirty-five percent aqueous NaOH was slowly added to
stirred suspension of 1 1.86 g (10 mmol) in 10 ml DMF
and then 2.5 g (1.7 equiv) of 1-bromo-2-chloroethane
was added. The temperature was maintained below
30 ꢁC. After 12 h of stirring, the solid was filtered and
washed with DMF. Filtrate and washings were com-
bined and evaporated to dryness (rotary evaporator,
bath temperature ca. 100–110 ꢁC). The yellow residue
was extracted with boiling MeCN. After evaporation
of the solvent, the residue was subjected to purification
by means of flash chromatography (silica gel, CHCl3/
MeOH/H2O, 5:0.2:0.02), yielded 0.15 g, 7%; mp 220–
223 ꢁC (CHCl3). IR kmax (KBr) cmꢁ1: 3404, 3057,
3042, 2930, 2863, 1636, 1474, 1426, 1348, 1336, 1266,
3.7. 2-(4,5-Dihydro-4-methyl-1H-imidazol-2-yl)-1H-
benzimidazole (7)
Yield 80%; mp 244–246 ꢁC (CHCl3), Ref. 19 253 ꢁC
(CHCl3).
Compound 7 · HCl, yield 97%; mp 292–293 ꢁC (EtOH).
IR kmax (KBr) cmꢁ1: 3358, 3137, 3092, 2980, 2818, 2740,
2564, 2475, 1654, 1636, 1610, 1478, 1443, 1325, 1274,
1004. 1H NMR (200 MHz, DMSO–d6) d: 1.38 (d,
J = 6.4 Hz, 3H, CH3), 3.66 (dd, J = 8.1 Hz,
J = 11.4 Hz, 1H, CH2), 4.20 (m, 1H, CH2), 4.55 (m,
1H, CH), 7.44 (m, 2H, aromat), 7.78 (m, 2H, aromat),
8.6–9.0 (bs, NH), 11.21 (s, 1H, NH), 11.40 (s, 1H, NH).
1
1194, 1182, 1128, 1044. H NMR (200 MHz, DMSO–
d6) d: 3.38 (m, 2 H, CH2), 3.51 (m, 2H, CH2), 3.82 (m,
2H, CH2), 4.47 (m, 2H, CH2), 7.34 (m, 2H, aromat),
7.66 (m, 1H, aromat), 7.75 (m, 1H, aromat). 13C
NMR (50 MHz, DMSO–d6) d: 41.4, 44.9, 51.8, 54.0,
111.3, 120.4, 123.2, 124.0, 134.0, 141.2, 143.1, 155.5.
3.8. 2-(4,5-Dihydrooxazol-2-yl)-1H-benzimidazole (10)
Compound 8 · HCl, yield 0.10 g, 90%; mp 262–265 ꢁC
(EtOH). IR kmax (KBr) cmꢁ1: 3345, 2965, 2923, 1653,
1631, 1478, 1346, 1316, 1286, 1200, 1133. 1H NMR
(500 MHz, DMSO–d6) d: 4.02 (m, 2H, CH2), 4.08 (m,
2H, CH2), 4.12 (m, 2H, CH2), 4.67 (m, 2H, CH2), 7.46
(m, 1H, aromat), 7.56 (m, 1H, aromat), 7.83 (d,
J = 8.3 Hz, 1H, aromat), 7.90 (d, J = 7.8 Hz, 1H, aro-
mat), 11.60 (bs, 1H, NH).
Yield 86%; mp 263–265 ꢁC (MeOH), Ref. 19 268 ꢁC
(MeOH). IR kmax (KBr) cmꢁ1: 3068, 2976, 2935, 2867,
2750, 2639, 1663, 1621, 1585, 1529, 1489, 1434, 1395,
1323, 1299, 1258, 1153, 1016.
Compound 10 · HCl, yield 90%; mp 296–299 ꢁC (EtOH).
IR kmax (KBr) cmꢁ1: 3420, 3090, 2988, 2478, 1750, 1610,
1551, 1522, 1499, 1360, 1313, 1255. 1H NMR (200 MHz,
DMSO–d6) d: 3.30 (m, 2H, CH2), 4.60 (m, 2H, CH2), 7.45
(m, 2H, aromat), 7.75 (m, 2H, aromat).
3.12. Preparation of 2,3,6,7-tetrahydro-5H-benzo[4,5]im-
idazo[1,2-a]imidazo[2,1-c][1,4]diazepine hydrobromide (9)
3.9. 2-(4,5-Dihydro-4,4-dimethyloxazol-2-yl)-1H-benz-
imidazole (11)
Thirty-five percent aqueous NaOH was slowly added to
stirred suspension of 1 4.00 g (21.5 mmol) in 20 ml DMF
and then 7.6 g (1.7 equiv) of 1,3-dibromopropane was
added. The temperature was maintained below 30 ꢁC.
After 48 h of stirring, the solid was filtered and washed
Yield 85%; mp 249–251 ꢁC (benzene), Ref. 19 250 ꢁC
(benzene). IR kmax (KBr) cmꢁ1: 3066, 2972, 2892,