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A. Khalafi-Nezhad et al. / Bioorg. Med. Chem. 13 (2005) 1931–1938
no further progress in reaction, the solvent was evapo-
rated and the crude mixture was suspended in water
(200 mL). The organic materials were extracted with
CHCl3 (2 · 100 mL) and dried over Na2SO4 (15 g). Fil-
tration and evaporation of the solvent gave the crude
product, which was purified by column chromatography
on silica gel with EtOAc/n-hexane (2:8).
(complex, 4H, OCH2, NCH2); 2.59–2.50 (q, J = 7.5,
2H, C(2)-CH2, imid.); 1.84–1.75 (m, 2H, CH2); 1.69–
1.59 (m, 2H, CH2); 1.23–1.17 (t, J = 7.5, 3H, Me). MS
[m/z (%)]: 279 (25.2). Anal. Calcd for C15H19ClN2O: C
64.63, H 6.87, Cl 17.72, N 10.05. Found: C 64.62, H
6.91, Cl 17.76, N 10.10.
6.2.5. 1-[4-(2,4-Dichlorophenoxy)butyl]-2-methyl-4-nitro-
1H-imidazole (4e). Pale yellow crystals (2.74 g, 81%). Rf
(EtOAc) 0.79. Mp 79–81 ꢁC. IR (KBr) 3200m, 2985m,
2850m, 1640m, 1610s, 1590s, 1420s, 1390s, 1255s,
6.2. General procedure for the preparation of compounds
4a–l and 5a–e
1
To solution of 3 (0.01 mol), imidazole (0.015 mol) or
benzimidazole (0.015 mol) and catalytic amount of
TBAB (0.1 g) in anhydrous MeCN (40 mL) was added
Et3N (1.01 g, 0.01 mol) and then solution was refluxed.
After 10 h, when TLC monitoring indicated disappear-
ance of the starting compound 3, the solvent was evap-
orated and the crude mixture was suspended in water
(200 mL). The organic materials were extracted with
CHCl3 (2 · 150 mL) and dried over Na2SO4 (20 g). Fil-
tration and evaporation of the solvent gave the crude
product, which was purified by column chromatography
on silica gel with EtOAc.
1000s. H NMR (CDCl3, 250 MHz) 7.85 (s, 1H, C(5)-
H, imid.); 7.21 (s, 1H, aryl); 7.12–7.09 (d, J = 8.8, 1H,
aryl); 6.78–6.74 (d, J = 8.8,1H, aryl); 4.05–3.97 (com-
plex, 4H, OCH2, NCH2); 2.73 (s, 3H, Me); 2.08–1.99
(m, 2H, CH2); 1.88–1.80 (m, 2H, CH2). MS [m/z (%)]:
344 (22.9). Anal. Calcd for C14H15Cl2N3O3: C 48.85,
H 4.39, Cl 20.60, N 12.21. Found: C 48.92, H 4.42, Cl
20.58, N 12.22.
6.2.6. 1-[4-(4-Chlorophenoxy)butyl]-2-methyl-4-nitro-1H-
imidazole (4f). Pale yellow crystals (2.48 g, 80%). Rf
(EtOAc) 0.86. Mp 51–53 ꢁC. IR (KBr) 3100m, 2980m,
2850m, 1645m, 1605s, 1590s, 1420s, 1395s, 1260s,
1
6.2.1. 1-[2-(2,4-Dichlorophenoxy)ethyl]-1H-imidazole (4a).
Brown oil (2.1 g, 80%). Rf (EtOAc) 0.51. IR (liquid film)
3200m, 2900m, 2850m, 1680m, 1600s, 1430s, 1260s,
1100s. H NMR (CDCl3, 250 MHz) 7.96 (s, 1H, C(5)-
H, imid.); 7.15–7.12 (d, J = 7.6, 2H, aryl); 6.73–6.70
(d, J = 7.6, 2H, aryl); 3.97–3.87 (complex, 4H, OCH2,
NCH2); 2.36 (s, 3H, Me); 1.96–1.90 (m, 2H, CH2);
1.78–1.76 (m, 2H, CH2). MS [m/z (%)]: 310 (71.5). Anal.
Calcd for C14H16ClN3O3: C 54.29, H 5.21, Cl 11.45, N
13.57. Found: C 54.32, H 5.25, Cl 11.52, N 13.58.
1
1100s. H NMR (CDCl3, 250 MHz) 7.62 (s, 1H, C(2)-
H, imid.); 7.25–6.62 (m, 5H, aryl, C(4)-H, C(5)-H,
imid.); 4.32–4.28 (t, J = 4.4, 2H, OCH2); 4.12–4.09 (t,
J = 4.4, 2H, NCH2). MS [m/z (%)]: 257 (12.2). Anal.
Calcd for C11H10Cl2N2O: C 51.38, H 3.92, Cl 27.58, N
10.90. Found: C 51.43, H 3.96, Cl 27.62, N 10.85.
6.2.7. 1-[5-(2,4-Dichlorophenoxy)pentyl]-1H-imidazole (4g).
Pale yellow crystals (2.40 g, 79%). Rf (EtOAc) 0.25. Mp
48–50 ꢁC. IR (KBr) 3150m, 2980m, 2890m, 1670m,
1610s, 1430s, 1280s, 1050s. 1H NMR (CDCl3,
250 MHz) 7.87 (s, 1H, C(2)-H, imid.); 7.46 (s, 1H, aryl)
7.07–7.04 (d, J = 8.8, 1H, aryl); 6.97–6.84 (m, 2H, C(4)-
H, C(5)-H, imid.); 6.73–6.69 (d, J = 8.8, 1H, aryl); 3.92–
3.86 (complex, 4H, OCH2, NCH2); 1.84–1.70 (m, 4H,
2CH2); 1.48–1.36 (m, 2H, CH2). MS [m/z (%)]: 299
(7.5). Anal. Calcd for C14H16Cl2N2O: C 56.20, H 5.39,
Cl 23.70, N 9.36. Found: C 56.23, H 5.42, Cl 23.68, N
9.42.
6.2.2. 1-[4-(2,4-Dichlorophenoxy)butyl]-1H-imidazole (4b).
Brown oil (1.99 g, 70%). Rf (EtOAc) 0.33. IR (liquid
film) 3200m, 2950m, 2868m, 1670m, 1600s, 1430s,
1
1270s, 1150s. H NMR (CDCl3, 250 MHz) 7.86 (s, 1H,
C(2)-H, imid.); 7.29–6.71 (m, 5H, aryl, C(4)-H, C(5)-
H, imid.); 4.03–3.97 (t, J = 6.9, 2H, OCH2); 3.95–3.90
(t, J = 5.8, 2H, NCH2); 2.02–1.90 (m, 2H, CH2); 1.79–
1.69 (m, 2H, CH2). MS [m/z (%)]: 285 (15). Anal. Calcd
for C13H14Cl2N2O: C 54.75, H 4.95, Cl 24.86, N 9.82.
Found: C 54.73, H 5.01, Cl 24.85, N 9.80.
6.2.3. 1-[4-(4-Chlorophenoxy)butyl]-1H-imidazole (4c).
Pale yellow oil (1.95 g, 70%). Rf (EtOAc) 0.44. IR (liquid
film) 3150m, 2985m, 2895m, 1675m, 1610s, 1425s, 1285s,
1100s. 1H NMR (CDCl3, 250 MHz) 7.38 (s, 1H, C(2)-H,
imid.); 7.09–7.05 (d, J = 8.7, 2H, aryl); 6.94–6.63 (m,
2H, C(4)-H, C(5)-H, imid.); 6.66–6.63 (d, J = 8.7, 2H,
aryl); 3.89–3.84 (t, J = 6.8, 2H, OCH2); 3.79–3.75 (t,
J = 5.9, 2H, NCH2); 1.88–1.77 (m, 2H, CH2); 1.66–
1.56 (m, 2H, CH2). MS [m/z (%)]: 251 (78.3). Anal.
Calcd for C13H15ClN2O: C 62.28, H 6.03, Cl 14.14, N
11.17. Found: C 62.24, H 5.97, Cl 14.16, N 11.22.
6.2.8.
1-[5-(2,4-Dichlorophenoxy)pentyl]-2-ethyl-1H-
imidazole (4h). White crystals (2.57 g, 79%). Rf (EtOAc)
0.44. Mp 54–56 ꢁC. IR (KBr) 3100m, 2985s, 2890m,
1650m, 1600s, 1420s, 1250s, 1100s. H NMR (CDCl3,
1
250 MHz) 7.21 (s, 1H, aryl); 7.03–6.99 (d, J = 8.8, 1H,
aryl); 6.90–6.79 (m, 2H, C(4)-H, C(5)-H, imid.); 6.71–
6.68 (d, J = 8.8, 1H, aryl); 3.87–3.82 (t, J = 6.0, 2H,
OCH2); 3.76–3.70 (t, J = 7.1, 2H, NCH2); 2.60–2.51 (q,
J = 7.5, 2H, C(2)-CH2, imid.); 1.77–1.63 (m, 4H,
2CH2); 1.46–1.34 (m, 2H, CH2); 1.25–1.19 (t, J = 7.5,
3H, Me). MS [m/z (%)]: 327 (10). Anal. Calcd for
C16H20Cl2N2O: C 58.72, H 6.16, Cl 21.67, N 8.56.
Found: C 58.70, H 6.20, Cl 21.60, N 8.50.
6.2.4. 1-[4-(4-Chlorophenoxy)butyl]-2-ethyl-1H-imidazole
(4d). Yellow oil (2.34 g, 84%). Rf (EtOAc) 0.40. IR (li-
quid film) 3150m, 2900s, 2895m, 1679m, 1610s, 1445s,
1265s, 1110s. 1H NMR (CDCl3, 250 MHz) 7.09–7.05
(d, J = 8.9, 2H, aryl); 6.81–6.71 (m, 2H, C(4)-H, C (5)-
H, imid.); 6.67–6.63 (d, J = 8.9, 2H, aryl); 3.80–3.74
6.2.9. 1-[5-(4-Chlorophenoxy)pentyl]-1H-imidazole (4i).
White crystals (2.35 g, 88%). Rf (EtOAc) 0.31. Mp 58–
60 ꢁC. IR (KBr) 3100m, 2985m, 2850m, 1640m, 1615s,
1
1430s, 1285s, 1050s. H NMR (CDCl3, 250 MHz) 7.45