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R. Torregrosa et al. / Tetrahedron 63 (2007) 469–473
14%), 166 (100), 139 (15), 137 (10), 109 (16), 107 (12), 98
(14), 96 (11), 95 (60), 83 (11), 82 (49), 81 (30), 79 (10), 70
(11), 69 (68), 68 (41), 67 (12), 55 (12), 53 (11).
EtOH, 98% ee from HPLC) [lit.15 [a]D25 ꢁ47.6 (c 1.0,
EtOH)]; dH (400 MHz, CDCl3): 3.25 (1H, s, OH), 4.10 (2H,
m, CH2), 4.88 (1H, m, CHOH), 6.89, 6.92 (1H and 1H, 2s,
NCHCHN), 7.27–7.37 (6H, m, ArH and NCHN); dC
(100 MHz, CDCl3): 54.5 (CH2), 73.1 (CHOH), 120.0, 125.7,
128.0, 128.1, 128.5 (7C, ArCH and NCHCHN), 137.5 (NCHN),
140.9 (ArC). The enantiomeric excess was determined by
chiral HPLC: Daicel Chiralcel OD-H, l¼210 nm, n-hexane/
2-propanol (90/10), 1 mL/min, tR¼40.15 min.
4.2.3. 1-(1H-Imidazol-1-yl)-2-octanol (3c). Dense pale yel-
low oil; tR 13.21; n (film) 3770–3005 cmꢁ1 (OH); dH
(400 MHz, CDCl3): 0.88 (3H, m, CH3), 1.23–1.39, 1.40–
1.52 (7H and 3H, respectively, 2m, 5ꢂCH2), 3.80 (2H, m,
NCH2), 3.93 (1H, m, CHOH), 5.46 (1H, br s, OH), 6.85,
6.90 (1H and 1H, 2s, NCHCHN), 7.34 (1H, s, NCHN); dC
(100 MHz, CDCl3): 14.1 (CH3), 22.6, 25.7, 29.3, 31.8,
34.6 (5ꢂCH2), 53.7 (NCH2), 70.5 (CHOH), 119.8, 128.3
(NCHCHN), 137.5 (NCHN); m/z 197 (M++1, 3%), 196
(16), 169 (11), 82 (100), 81 (47), 69 (19), 55 (24). HRMS
calcd for C11H20N2O 196.1576, found 196.1565.
4.4. General procedure for the ring opening
of epoxides with benzimidazole
A mixture of benzimidazole (20 mmol, 2.40 g) and epoxide
(20 mmol) was placed in a round bottom flask and stirred at
60 ꢀC (except for the epoxide 2f: carried out at 45 ꢀC) for
12 h. The resulting mixture was purified by recrystallization
(normally using acetone/hexane) and/or by column chroma-
tography (silica gel, mixtures of ethyl acetate and methanol
from 20:1 to 30:1) to yield the corresponding products 5.
Yields are included in Table 3, physical, spectroscopic, and
analytical data, as well as literature references for known
compounds, follow.
4.2.4. 1-(1H-Imidazol-1-yl)-3-phenoxy-2-propanol
(3d).11 Dense colorless oil; tR 15.16; n (film) 3716–
2988 cmꢁ1 (OH); dH (400 MHz, CDCl3): 3.80, 3.97, 4.05,
4.18–4.21 (1H, 1H, 1H, and 2H, respectively, 3dd, J¼9.3,
6.8 Hz, J¼9.3, 4.6 Hz, J¼14.8, 7.7 Hz and 1m, respectively,
2ꢂCH2 and CHOH), 6.85–6.97, 7.26 (5H and 2H, respec-
tively, 2m, ArH and NCHCHN), 7.39 (1H, s, NCHN); dC
(100 MHz, CDCl3): 50.5 (NCH2), 68.5 (CHOH), 68.6
(OCH2), 114.5, 120.2, 121.3, 128.1, 129.6 (7C, ArCH and
NCHCHN), 137.7 (NCHN), 158.2 (ArC); m/z 219 (M++1,
15%), 218 (100), 125 (15), 107 (20), 94 (26), 82 (96),
81 (62), 77 (28), 55 (10), 54 (14). HRMS calcd for
C12H14N2O2 218.1055, found 218.1073.
4.4.1. 2-(1H-Benzimidazol-1-yl)-1-phenylethanol (5a).8
Amber solid; mp 88–89 ꢀC (acetone/hexane); tR 16.72; n
(KBr) 3725–2963 cmꢁ1 (OH); dH (400 MHz, CDCl3): 4.19
(1H, dd, J¼14.4, 8.3 Hz, CHH), 4.26 (1H, dd, J¼14.4,
3.5 Hz, CHH), 5.04 (1H, dd, J¼8.3, 3.5 Hz, CHOH), 5.80
(1H, br s, OH), 7.07–7.42, 7.56 (9H and 1H, respectively,
m and s, respectively, ArH and NCHN); dC (100 MHz,
CDCl3): 53.1 (CH2), 72.0 (CHOH), 109.7, 119.7, 122.2,
123.0, 126.0, 128.3, 128.8 (9C, ArCH), 133.6, 141.4, 142.8
(ArC), 143.7 (NCHN); m/z 239 (M++1, 5%), 238 (29), 132
(100), 131 (74), 107 (16), 104 (11), 79 (19), 77 (30).
4.2.5. 1-(1H-Imidazol-1-yl)-3-phenyl-2-propanol (3e).
Colorless oil; tR 14.49; n (film) 3745–2973 cmꢁ1 (OH); dH
(300 MHz, CDCl3): 2.70 (1H, dd, J¼13.7, 5.9 Hz, CHHPh),
2.80 (1H, dd, J¼13.7, 7.3 Hz, CHHPh), 3.77 (1H, dd,
J¼14.0, 7.9 Hz, NCHH), 3.92 (1H, dd, J¼14.0, 2.8 Hz,
NCHH), 4.02 (1H, m, CHOH), 5.24 (1H, br s, OH), 6.77,
6.85 (1H and 1H, 2s, NCHCHN), 7.18–7.32 (6H, m, ArH
and NCHN); dC (75 MHz, CDCl3): 41.2 (CH2Ph), 52.5
(NCH2), 71.3 (CHOH), 119.7, 126.5 (NCHCHN), 128.1,
128.5, 129.3 (5C, ArCH), 137.3 (NCHN), 137.6 (ArC);
m/z 203 (M++1, 8%), 202 (49), 184 (23), 121 (14), 117 (30),
103 (31), 92 (12), 91 (62), 83 (13), 82 (100), 81 (52), 77 (12),
65 (16), 55 (12), 54 (11). HRMS calcd for C12H14N2O
202.1106, found 202.1110.
4.4.2. trans-2-(1H-Benzimidazol-1-yl)cyclohexanol (5b).
Beige solid; mp 164–165 ꢀC (acetone/hexane); tR 15.55;
n (KBr) 3702–2982 cmꢁ1 (OH); dH (300 MHz, CDCl3):
1.41–1.63, 1.73–1.93, 2.01–2.06, 2.24–2.28 (3H, 3H, 1H,
and 1H, 4m, 4ꢂCH2), 3.92–4.05 (2H, m, 2ꢂCH ring),
7.08–7.13, 7.19–7.24, 7.42–7.46 (1H, 1H, and 3H, 3m,
ArH and NCHN); dC (300 MHz, CDCl3): 24.5, 25.3, 31.9,
34.4 (4ꢂCH2), 62.5 (CHN ring), 72.2 (CHOH), 110.6,
119.4, 122.1, 122.6 (ArCH), 133.8, 142.8 (ArC), 140.7
(NCHN); m/z 218 (M++2, 1%), 217 (15), 216 (100), 187
(14), 159 (32), 157 (32), 145 (49), 132 (60), 131 (23), 119
(28), 118 (45). HRMS calcd for C13H16N2O 216.1263, found
216.1264.
4.2.6. 1-(1H-Imidazol-1-yl)-2-methyl-2-propanol (3f).
Dense amber oil; tR 9.15; n (film) 3722–3015 cmꢁ1 (OH);
dH (400 MHz, CDCl3): 1.63 (6H, s, 2ꢂCH3), 4.14 (1H,
br s, OH), 4.26 (2H, s, CH2), 7.33 (2H, s, CHCH), 7.85
(1H, s, NCHN); dC (100 MHz, CDCl3): 27.2 (2C, 2ꢂCH3),
58.2 (CH2), 69.8 (COH), 120.8, 128.1 (CHCH), 138.2
(NCHN); m/z 141 (M++1, 3%), 140 (36), 125 (13), 82
(100), 81 (72), 59 (58), 55 (12), 54 (14). HRMS calcd for
C7H12N2O 140.0950, found 140.0947.
4.4.3. 1-(1H-Benzimidazol-1-yl)-2-octanol (5c). Beige
solid; mp 61–62 ꢀC (ether); tR 16.22; n (KBr) 3725–
3009 cmꢁ1 (OH); dH (300 MHz, CDCl3): 0.90 (3H, m,
CH3), 1.32–1.59 (10H, m, 5ꢂCH2), 3.93–4.00, 4.17 (2H
and 1H, respectively, 2m, NCH2 and CHOH), 4.97 (1H,
br s, OH), 7.06, 7.17 (1H and 1H, 2m, ArH), 7.31, 7.39
(1H and 1H, 2d, J¼8.1 Hz, ArH), 7.64 (1H, s, NCHN); dC
(75 MHz, CDCl3): 14.0 (CH3), 22.6, 25.7, 29.2, 31.7, 34.7
(5ꢂCH2), 51.6 (NCH2), 69.6 (CHOH), 109.6, 119.5,
122.0, 122.7 (ArCH), 133.6, 142.8 (ArC), 143.5 (NCHN);
m/z 247 (M++1, 6%), 246 (31), 133 (11), 132 (100), 131
(77), 119 (17), 104 (13), 77 (12). HRMS calcd for
C15H22N2O 246.1732, found 246.1721.
4.3. (R)-2-(1H-Imidazol-1-yl)-1-phenylethanol
[(R)-3a]15
A mixture of imidazole (2 mmol, 0.138 g) and (R)-styrene
oxide (2 mmol, 0.236 mL) was placed in a round bottom
flask and stirred at 60 ꢀC for 12 h. The resulting mixture
was purified by recrystallization (acetone/hexane) giving
0.233 g (62% yield) of a white solid; [a]2D0 ꢁ45.7 (c 1.0,