The combined 1 M NaOH solution layer was neutralized with
10% NaHSO4 solution and extracted with AcOEt (200 mL).
The organic layer was washed with brine (100 mL) and dried
over MgSO4. The solvent was evaporated off, and the residue
was triturated with Et2O (20 mL) and then filtered to give 1.
2-OH); δC 20.6, 41.9, 67.3, 115.3, 127.1, 128.9, 133.8, 136.4,
144.8, 149.8; m/z (EI) 228 (Mϩ, 27%), 105 (100).
5-Amino-1-(4-chlorobenzyl)-4-cyano-2-hydroxyimidazole 1g.
Yield 50%; mp 198–199 ЊC (washed with AcOEt) (Found: C,
53.14; H, 3.72; N, 22.42. Calc. for C11H9ClN4O: C, 53.13; H,
3.65; N, 22.53%); λmax(EtOH–H2O = 1 : 9)/nm 266.6 (ε/dm3
molϪ1 cmϪ1 13 100); νmax/cmϪ1 3330, 3217, 2197, 1713, 1650,
1495, 1412, 1346, 1095; δH 4.74 (2 H, s, 1-CH2), 6.51 (2 H, s*,
5-NH2), 7.25 and 7.39 (each 2 H, each d, J 8.5, 1-Ar), 9.92 (1 H,
s*, 2-OH); δC 41.5, 67.5, 115.2, 128.4, 129.0, 132.0, 135.8, 144.6,
149.7; m/z (EI) 250 (Mϩ ϩ 2, 9%), 248 (Mϩ, 29), 127 (31), 125
(100) [Found: HRMS (EI) m/z 248.0460. Calc. for C11H9ClN4O:
(Mϩ) 248.0465].
5-Amino-1-benzyl-4-cyano-2-hydroxyimidazole 1a. Yield
85%; mp 216–218 ЊC (recrystallized from AcOEt) (Found: C,
61.61; H, 4.82; N, 25.95. Calc. for C11H10N4O: C, 61.67; H, 4.71;
N, 26.15%); λmax(EtOH–H2O = 1 : 9)/nm 269.0 (ε/dm3 molϪ1
cmϪ1 13 800); νmax/cmϪ1 3456, 2202, 1720, 1652, 1494, 737;
δH 4.75 (2 H, s, 1-CH2), 6.48 (2 H, s*, 5-NH2), 7.20–7.36 (5 H,
m, 1-Ph), 9.89 (1 H, s*, 2-OH); δC 42.1, 67.4, 115.3, 127.0,
127.3, 128.4, 136.8, 144.8, 149.8; m/z (EI) 214 (Mϩ, 33%), 91
(100).
5-Amino-4-cyano-1-(4-fluorobenzyl)-2-hydroxyimidazole 1h.
Yield 54%; mp 213–215 ЊC (washed with AcOEt) (Found: C,
56.67; H, 3.85; N, 24.04. Calc. for C11H9FN4O: C, 56.89; H,
3.91; N, 24.13%); λmax(EtOH–H2O = 1 : 9)/nm 264.8 (ε/dm3
molϪ1 cmϪ1 13 500); νmax/cmϪ1 3325, 3187, 2200, 1706, 1653,
1511, 1345, 1231, 777; δH 4.73 (2 H, s, 1-CH2), 6.50 (2 H, s*,
5-NH2), 7.15 (2 H, t, J 8.8, 1-Ar), 7.29 (2 H, dd, J 5.6 and
8.8, 1-Ar), 9.90 (1 H, s*, 2-OH); δC 41.5, 67.4, 115.1, 115.2,
115.3, 129.2, 129.3, 133.0, 144.6, 149.7, 160.2, 162.6; m/z (EI)
232 (Mϩ, 29%), 109 (100) [Found: HRMS (EI) m/z 232.0753.
Calc. for C11H9FN4O: (Mϩ) 232.0760].
5-Amino-4-cyano-2-hydroxy-1-(2-methoxybenzyl)imidazole
1b. Yield 41%; mp 230–232 ЊC (recrystallized from EtOH)
(Found: C, 58.99; H, 5.01; N, 22.90. Calc. for C12H12N4O2: C,
59.01; H, 4.95; N, 22.94%); λmax(EtOH–H2O = 1 : 9)/nm 269.4
(ε/dm3 molϪ1 cmϪ1 14 600); νmax/cmϪ1 3456, 2194, 1680, 1634,
1494, 1249, 760, 632; δH 3.82 (3 H, s, 1-CH3), 4.70 (2 H, s,
1-CH2), 6.37 (2 H, s*, 5-NH2), 6.70 (1 H, d, J 7.7, 1-Ar), 6.89
(1 H, t, J 7.7, 1-Ar), 7.01 (1 H, d, J 7.7, 1-Ar), 7.25 (1 H, t, J 7.7,
1-Ar), 9.90 (1 H, s*, 2-OH); δC 38.0, 55.3, 67.4, 110.6, 115.3,
120.3, 124.3, 125.8, 128.3, 145.1, 149.6, 156.2; m/z (EI) 244
(Mϩ, 26%), 121 (100), 91 (75).
5-Amino-4-cyano-1-(2,5-difluorobenzyl)-2-hydroxyimidazole
1i. Yield 92%; mp 223–225 ЊC (washed with AcOEt) (Found: C,
52.03; H, 3.40; N, 21.79. Calc. for C11H8F2N4Oؒ1/4 H2O: C,
51.87; H, 3.36; N, 22.00%); λmax(EtOH–H2O = 1 : 9)/nm 267.6
(ε/dm3 molϪ1 cmϪ1 13 000); νmax/cmϪ1 3336, 3228, 2204, 1709,
1656, 1499, 1347, 1196, 742; δH 4.81 (2 H, s, 1-CH2), 6.50 (2 H,
s*, 5-NH2), 6.73–6.77 (1 H, m, 1-Ar), 7.15–7.20 (1 H, m, 1-Ar),
7.24–7.30 (1 H, m, 1-Ar), 9.99 (1 H, br s*, 2-OH); δC 36.9, 68.0,
114.2, 114.3, 114.50, 114.54, 115.1, 115.4, 115.5, 115.6, 115.7,
116.8, 116.9, 117.0, 117.1, 125.6, 125.7, 125.8, 125.9, 144.6,
149.5, 154.6, 156.9, 157.0, 159.3; m/z (EI) 250 (Mϩ, 47%), 127
(100) [Found: HRMS (EI) m/z 250.0658. Calc. for C11H8F2N4O:
(Mϩ) 250.0666].
5-Amino-4-cyano-2-hydroxy-1-(3-methoxybenzyl)imidazole
1c. Yield 54%; mp 222–224 ЊC (washed with AcOEt) (Found: C,
58.97; H, 4.97; N, 22.84. Calc. for C12H12N4O2: C, 59.01; H,
4.95; N, 22.94%); λmax(EtOH–H2O = 1 : 9)/nm 268.2 (ε/dm3
molϪ1 cmϪ1 15 400); νmax/cmϪ1 3429, 3322, 3228, 2200, 1706,
1651, 1606, 1495, 1348, 1258, 1050, 767; δH 3.71 (3 H, s, 1-CH3),
4.72 (2 H, s, 1-CH2), 6.47 (2 H, s*, 5-NH2), 6.77–6.84 (3 H, m,
1-Ar), 7.23 (1 H, t, J 7.8, 1-Ar), 9.89 (1 H, s*, 2-OH); δC 42.1,
55.0, 67.4, 112.4, 113.1, 115.3, 119.1, 129.5, 138.3, 144.7, 149.8,
159.2; m/z (EI) 244 (Mϩ, 38%), 121 (100), 91 (17).
5-Amino-4-cyano-2-hydroxy-1-(4-methoxybenzyl)imidazole
1d. Yield 41%; mp 214–216 ЊC (washed with AcOEt) (Found: C,
58.64; H, 4.96; N, 22.77. Calc. for C12H12N4O2ؒ1/10 H2O: C,
58.58; H, 5.00; N, 22.77%); λmax(EtOH–H2O = 1 : 9)/nm 268.4
(ε/dm3 molϪ1 cmϪ1 14 500); νmax/cmϪ1 3425, 3327, 3222, 2201,
1716, 1657, 1513, 1249, 1178, 1026; δH 3.71 (3 H, s, 1-CH3), 4.67
(2 H, s, 1-CH2), 6.47 (2 H, s*, 5-NH2), 6.87 and 7.20 (each 2 H,
each d, J 8.3, 1-Ar), 9.85 (1 H, s*, 2-OH); δC 41.6, 55.0, 67.3,
113.8, 115.3, 128.7, 128.8, 144.7, 149.8, 158.6; m/z (EI) 244
(Mϩ, 10%), 121 (100) [Found: HRMS (EI) m/z 244.0954. Calc.
for C12H12N4O2: (Mϩ) 244.0960].
5-Amino-4-cyano-2-hydroxy-1-(ꢀ-naphthylmethyl)imidazole
1j. Yield 75%; mp 242–244 ЊC; λmax(EtOH–H2O = 1 : 9)/nm
268.8 (ε/dm3 molϪ1 cmϪ1 16 200); δH 5.26 (2 H, s, 1-CH2), 6.48
(2 H, s*, 5-NH2), 6.90 (1 H, d, J 7.7, 1-Ar), 7.45 (1 H, t, J 7.7,
1-Ar), 7.56–7.61 (2 H, m, 1-Ar), 7.84 (1 H, d, J 7.7, 1-Ar),
7.97 (1 H, d, J 7.3, 1-Ar), 8.15 (1 H, d, J 8.8, 1-Ar), 9.97 (1 H,
br s*, 2-OH); m/z (EI) 264 (Mϩ, 20%), 141 (100), 115 (21)
[Found: HRMS (EI) m/z 264.0980. Calc. for C15H12N4O: (Mϩ)
264.1011].
5-Amino-4-cyano-1-(3,4-dimethoxybenzyl)-2-hydroxyimid-
azole 1e. Yield 58%; mp 189–190 ЊC (washed with AcOEt)
(Found: C, 56.75; H, 5.11; N, 20.30. Calc. for C13H14N4O3: C,
56.93; H, 5.14; N, 20.43%); λmax(EtOH–H2O = 1 : 9)/nm 269.8
(ε/dm3 molϪ1 cmϪ1 13 900); νmax/cmϪ1 3381, 3208, 2198, 1721,
1654, 1517, 1259, 1144, 1026; δH 3.70 and 3.71 (each 3 H, each s,
1-CH3), 4.66 (2 H, s, 1-CH2), 6.45 (2 H, s*, 5-NH2), 6.76 (1 H,
dd, J 2.0 and 8.1, 1-Ar), 6.88 (1 H, d, J 8.1, 1-Ar), 6.96 (1 H, d,
J 2.0, 1-Ar), 9.85 (1 H, s*, 2-OH); δC 41.9, 55.4, 55.5, 67.3,
111.6, 111.8, 115.3, 119.5, 129.2, 144.7, 148.2, 148.5, 149.8;
m/z (EI) 274 (Mϩ, 14%), 151 (100).
5-Amino-4-cyano-2-hydroxy-1-phenylimidazole 1k. Yield
73%; mp 222–223 ЊC (washed with AcOEt) (Found: C, 57.38;
H, 4.32; N, 26.78. Calc. for C10H8N4Oؒ1/2 H2O: C, 57.41; H,
4.34; N, 26.78%); λmax(EtOH–H2O = 1 : 9)/nm 263.6 (ε/dm3
molϪ1 cmϪ1 13 200); νmax/cmϪ1 3432, 3299, 3159, 2198, 1707,
1642, 1498, 1294, 1108, 763; δH 6.13 (2 H, s*, 5-NH2), 7.31 (2 H,
d, J 7.8, 1-Ph), 7.41–7.51 (3 H, m, 1-Ph), 10.04 (1 H, s*, 2-OH);
δC 68.3, 115.1, 127.9, 128.4, 129.3, 132.3, 144.2, 149.2; m/z (EI)
200 (Mϩ, 100%), 171 (48), 119 (41), 77 (34) [Found: HRMS (EI)
m/z 200.0695. Calc. for C10H8N4O: (Mϩ) 200.0698].
5-Amino-1-butyl-4-cyano-2-hydroxyimidazole 1l. Yield 22%;
mp 140–142 ЊC (washed with AcOEt) (Found: C, 52.79; H,
6.64; N, 30.63. Calc. for C8H12N4Oؒ1/10 H2O: C, 52.79; H, 6.76;
N, 30.78%); λmax(EtOH–H2O = 1 : 9)/nm 263.8 (ε/dm3 molϪ1
cmϪ1 14 000); νmax/cmϪ1 3210, 2195, 1706, 1649, 1500; δH 0.86
(3 H, t, J 7.6, 1-CH3), 1.18–1.27 (2 H, m, 1-CH2), 1.41–1.48
(2 H, m, 1-CH2), 3.48 (2 H, t, J 7.3, 1-CH2), 6.39 (2 H, s*,
5-NH2), 9.71 (1 H, s*, 2-OH); δC 13.6, 19.2, 30.0, 67.0, 115.5,
5-Amino-4-cyano-2-hydroxy-1-(4-methylbenzyl)imidazole 1f.
Yield 58%; mp 208–210 ЊC (washed with AcOEt) (Found: C,
62.99; H, 5.27; N, 24.33. Calc. for C12H12N4O: C, 63.15; H, 5.30;
N, 24.55%); λmax(EtOH–H2O = 1 : 9)/nm 266.8 (ε/dm3 molϪ1
cmϪ1 12 700); νmax/cmϪ1 3423, 3202, 2213, 1691, 1655, 1492,
1345, 762; δH 2.25 (3 H, s, 1-CH3), 4.70 (2 H, s, 1-CH2), 6.46
(2 H, s*, 5-NH2), 7.11–7.12 (4 H, m, 1-Ar), 9.86 (1 H, br s*,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 5 4 – 1 3 6 5
1357