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G. Roman et al.
Arch. Pharm. Chem. Life Sci. 2013, 346, 110–118
(d, J ¼ 7.6 Hz, 2H), 7.27 (d, J ¼ 8.0 Hz, 1H), 7.35 (d, J ¼ 7.6 Hz,
2H), 7.53–7.60 (m, 1H), 7.63–7.69 (m, 3H), 9.13 (s, 1H); 13C NMR
(d6-DMSO): d 20.8, 43.5, 44.0, 70.1, 114.0, 119.5, 120.7, 122.0,
126.7, 128.0, 129.0, 129.8, 133.2, 134.5, 135.4, 137.4, 157.9,
197.7; Anal. calcd. for C20H21ClN2O2: C 67.32, H 5.93, N 7.85.
Found: C 67.11, H 6.03, N 8.02.
under good stirring, at room temperature. The reaction mixture
was then stirred at room temperature overnight. The solvent was
removed under reduced pressure, and the residue was parti-
tioned between water (30 mL) and ethyl acetate (15 mL).
The aqueous phase was further extracted with ethyl acetate
(15 mL), the organic phases were combined, washed with water
(15 mL) and brine (10 mL), and dried over anhydrous Na2SO4.
The solvent was then removed under reduced pressure to give
a residue. In the case of compounds 47, 48, and 50–53, the
residue was crystallized from the appropriate solvent. The
other imidazole–alcohols were converted into the corresponding
hydrochlorides by treating a solution of the residue in a
mixture of 2-propanol (4 mL) and diethyl ether (20–30 mL) with
an excess of ethereal hydrogen chloride. After being kept at
room temperature overnight, the crystals were filtered, washed
with diethyl ether, and recrystallized from the appropriate
solvent to yield the imidazole–alcohol hydrochlorides 44–46,
49, and 54.
1-(2 0-(4-Chlorobenzyloxy)phenyl)-3-(1H-imidazol-1-yl)-1-
propanone hydrochloride 40
Colorless crystals, 1220 mg (81%), mp 177–1788C (ethanol);
1H NMR (d6-DMSO): d 3.64 (t, J ¼ 6.6 Hz, 2H), 4.49 (t, J ¼ 6.6 Hz,
2H), 5.25 (s, 2H), 7.06 (t, J ¼ 7.6 Hz, 1H), 7.26 (d, J ¼ 8.4 Hz, 1H),
7.44 (d, J ¼ 8.4 Hz, 2H), 7.52 (d, J ¼ 8.4 Hz, 2H), 7.53–7.60 (m, 1H),
7.64 (t, J ¼ 1.6 Hz, 1H), 7.67 (dd, J ¼ 1.6 and 7.6 Hz, 1H), 7.71
(t, J ¼ 1.6 Hz, 1H), 9.17 (s, 1H); 13C NMR (d6-DMSO): d 43.3, 44.0,
69.3, 113.9, 119.5, 120.9, 122.0, 126.7, 128.5, 129.7, 129.8, 132.6,
134.4, 135.4, 135.5, 157.5, 197.7; Anal. calcd. for C19H18Cl2N2O2:
C 60.49, H 4.81, N 7.43. Found: C 60.62, H 4.89, N 7.28.
(ꢀ)-3-(1H-Imidazol-1-yl)-1-phenyl-1-propanol
1-(2 0-(4-Bromobenzyloxy)phenyl)-3-(1H-imidazol-1-yl)-1-
propanone hydrochloride 41
hydrochloride 44
Off-white crystals, 385 mg (54%), mp 100–1018C (2-propanol–
hexanes); 1H NMR (d6-DMSO): d 2.03–2.25 (m, 2H), 4.26–4.40
(m, 2H), 4.54 (dd, J ¼ 3.8 and 9.0 Hz, 1H), 5.68 (br s, 1H), 7.19–
7.37 (m, 5H), 7.67 (t, J ¼ 1.6 Hz, 1H), 7.83 (t, J ¼ 1.6 Hz, 1H), 9.23
(s, 1H), 14.93 (br s, 1H); 13C NMR (d6-DMSO): d 38.8, 46.0, 69.1,
119.6, 122.0, 125.6, 126.9, 128.1, 135.3, 145.1; Anal. calcd.
for C12H15ClN2O: C 60.38, H 6.33, N 11.74. Found: C 60.52, H
6.21, N 11.62.
Off-white crystals, 1435 mg (85%), mp 178–1798C (ethanol);
1H NMR (d6-DMSO): d 3.64 (t, J ¼ 6.8 Hz, 2H), 4.49 (t, J ¼ 6.8 Hz,
2H), 5.24 (s, 2H), 7.06 (t, J ¼ 7.4 Hz, 1H), 7.25 (d, J ¼ 8.4 Hz, 1H),
7.45 (d, J ¼ 8.4 Hz, 2H), 7.53–7.61 (m, 3H), 7.64 (s, 1H), 7.67
(dd, J ¼ 1.6 and 7.6 Hz, 1H), 7.72 (s, 1H), 9.17 (s, 1H); 13C NMR
(d6-DMSO): d 43.2, 44.0, 69.3, 113.9, 119.5, 120.9, 121.2, 122.0,
126.7, 129.8, 130.0, 131.4, 134.4, 135.5, 135.8, 157.5, 197.7; Anal.
calcd. for C19H18BrClN2O2: C 54.11, H 4.30, N 6.64. Found: C
54.27, H 4.16, N 6.83.
(ꢀ)-1-(4-Chlorophenyl)-3-(1H-imidazol-1-yl)-1-propanol
hydrochloride 45
1-(2 0-(3,4-Dichlorobenzyloxy)phenyl)-3-(1H-imidazol-1-
yl)-1-propanone hydrochloride 42
Colorless crystals, 345 mg (42%), mp 149–1508C (2-propanol–
diethyl ether); 1H NMR (d6-DMSO): d 2.01–2.13 (m, 1H), 2.13–
2.25 (m, 1H), 4.24–4.38 (m, 2H), 4.55 (dd, J ¼ 3.6 and 9.2 Hz,
1H), 5.81 (br s, 1H), 7.37 (s, 4H), 7.67 (s, 1H), 7.83 (s, 1H), 9.23
(s, 1H), 14.91 (br s, 1H); 13C NMR (d6-DMSO): d 38.6, 45.9, 68.4,
119.6, 122.1, 127.6, 128.0, 131.4, 135.3, 144.2; Anal. calcd.
for C12H14Cl2N2O: C 52.76, H 5.17, N 10.26. Found: C 52.60,
H 5.32, N 10.07.
Colorless crystals, 1270 mg (77%), mp 164–1658C (ethanol);
1H NMR (d6-DMSO): d 3.66 (t, J ¼ 6.8 Hz, 2H), 4.49 (t, J ¼ 6.8 Hz,
2H), 5.27 (s, 2H), 7.07 (t, J ¼ 7.6 Hz, 1H), 7.24 (d, J ¼ 8.0 Hz, 1H),
7.49 (dd, J ¼ 1.6 and 8.0 Hz, 1H), 7.54–7.61 (m, 1H), 7.62–7.67
(m, 2H), 7.69 (dd, J ¼ 1.6 and 7.6 Hz, 1H), 7.73 (s, 1H), 7.78
(d, J ¼ 1.6 Hz, 1H), 9.18 (s, 1H); 13C NMR (d6-DMSO): d 43.2,
44.0, 68.6, 113.9, 119.5, 121.0, 122.0, 126.7, 128.0, 129.7,
129.9, 130.6, 130.7, 131.1, 134.5, 135.5, 137.6, 157.3, 197.6;
Anal. calcd. for C19H17Cl3N2O2: C 55.43, H 4.16, N 6.80. Found:
C 55.25, H 4.33, N 6.68.
(ꢀ)-1-(4-Bromophenyl)-3-(1H-imidazol-1-yl)-1-propanol
hydrochloride 46
Off-white crystals, 665 mg (70%), mp 165–1668C (2-propanol–
diethyl ether); 1H NMR (d6-DMSO): d 2.00–2.13 (m, 1H), 2.13–
2.25 (m, 1H), 4.24–4.38 (m, 2H), 4.54 (dd, J ¼ 3.6 and 9.2 Hz,
1H), 5.80 (br s, 1H), 7.31 (d, J ¼ 8.4 Hz, 2H), 7.51 (d, J ¼ 8.4 Hz,
2H), 7.67 (t, J ¼ 1.6 Hz, 1H), 7.83 (t, J ¼ 1.6 Hz, 1H), 9.22 (s, 1H),
(ꢀ)-2-(1H-Imidazol-1-ylmethyl)-3,4-dihydronaphthalen-
1(2H)-one hydrochloride 43
Off-white crystals, 545 mg (52%), mp 156–1578C (2-propanol);
1H NMR (d6-DMSO): d 1.73–1.88 (m, 1H), 1.99–2.09 (m, 1H), 2.92–
3.14 (m, 2H), 3.30–3.43 (m, 1H), 4.45 (dd, J ¼ 6.4 and 13.6 Hz, 1H),
4.71 (dd, J ¼ 6.0 and 14.0 Hz, 1H), 7.32–7.40 (m, 2H), 7.54–7.61
(m, 1H), 7.69 (t, J ¼ 1.6 Hz, 1H), 7.79 (t, J ¼ 1.6 Hz, 1H), 7.88
(d, J ¼ 7.2 Hz, 1H), 9.24 (s, 1H); 13C NMR (d6-DMSO): d 26.1, 27.9,
46.8, 48.4, 119.6, 122.6, 126.5, 126.7, 129.1, 131.5, 133.9, 135.9,
144.2, 197.1; Anal. calcd. for C14H15ClN2O: C 64.00, H 5.75, N 10.66.
Found: C 64.26, H 5.51, N 10.47.
14.89 (br s, 1H); 13C NMR (d6-DMSO):
d 38.6, 45.9, 68.5,
119.6, 119.9, 122.0, 127.9, 131.0, 135.3, 144.6; Anal. calcd.
for C12H14BrClN2O: C 45.38, H 4.44, N 8.82. Found: C 45.54,
H 4.26, N 9.01.
(ꢀ)-1-(4-Biphenyl-1-yl)-3-(1H-imidazol-1-yl)-1-propanol 47
Colorless crystals, 590 mg (71%), mp 141–1428C (2-propanol)
(lit. mp 144–1458C [34]); 1H NMR (CDCl3): d 2.04–2.25 (m, 2H),
3.99–4.09 (m, 1H), 4.19–4.29 (m, 1H), 4.53 (dd, J ¼ 3.6 and 8.8 Hz,
1H), 4.58 (br s, 1H), 6.93 (s, 1H), 6.97 (s, 1H), 7.31–7.47 (m, 6H),
7.53–7.60 (m, 4H); 13C NMR (CDCl3): d 40.0, 43.8, 69.9, 118.9,
126.3, 127.2, 127.4, 127.5, 128.9, 129.3, 137.5, 140.7, 140.8,
General procedure for the reduction of imidazole–ketones
To the solution of imidazole–ketone (3 mmol) in methanol
(20 mL), NaBH4 (342 mg, 9 mmol) was added in small portions,
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