W. A. Szarek et al.
MED
[D6]DMSO): d=54.9, 116.2 (d, J2C,F =22 Hz), 119.3, 123.5, 130.6 (d,
J4C,F =2.5 Hz), 131.2 (d, J3C,F =9.6 Hz), 136.5, 165.6 (d, J1C,F =252 Hz),
190.2 ppm; 19F NMR (376 MHz, [D6]DMSO): d=104.8 ppm (septet);
HRMS-ESI m/z [MÀCl]+ calcd for C11H10FN2O: 205.0777, found:
205.0773.
2H), 9.16 ppm (brs, 1H); 13C NMR (100 MHz, [D6]DMSO): d=55.0,
119.3, 123.5, 127.0, 127.1, 128.6, 128.8, 129.1, 132.5, 136.5, 138.5,
145.6, 191.0 ppm; HRMS-ESI m/z [MÀCl]+ calcd for C17H15N2O:
263.1184, found: 263.1180.
1-(4’-Bromobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethanone
(37):
1-(4-Chlorophenyl)-2-(1H-imidazol-1-yl)ethanone hydrochloride
(31·HCl): The free base was prepared according to Method A in
56% yield; mp: 158–1598C (2-propanol) (lit.[23] mp: 160–160.58C);
1H NMR (400 MHz, CDCl3): d=5.37 (s, 2H), 6.93 (s, 1H), 7.13 (s, 1H),
7.47–7.58 (m, 3H), 7.90 ppm (dd, J=2.0 and 6.8 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=52.5, 120.3, 129.5, 129.6, 129.8, 132.6, 138.2,
141.1, 190.7 ppm. The free base 31 (221 mg, 1 mmol) was convert-
ed into the hydrochloride (31·HCl) in the usual manner, which was
obtained as a white solid (140 mg, 54%); mp: 227–2288C (2-propa-
Method B gave a mixture from which the desired compound was
separated using column chromatography (silica gel, EtOAc/MeOH
9:1). Recrystallization from EtOH afforded the product as a white
solid (471 mg, 46%); mp: 223–2258C; 1H NMR (400 MHz,
[D6]DMSO): d=5.77 (s, 2H), 6.94 (s, 1H), 7.14 (s, 1H), 7.61 (s, 1H),
7.71 (d, J=8.4 Hz, 2H), 7.75 (d, J=8.4 Hz, 2H), 7.91 (d, J=8.4 Hz,
2H), 8.12 ppm (d, J=8.4 Hz, 2H); 13C NMR (100 MHz, [D6]DMSO):
d=52.6, 120.9, 122.2, 127.0, 127.9, 128.8, 129.2, 132.0, 133.6, 137.9,
138.4, 143.8, 193.2 ppm; HRMS-EI m/z [M]+ calcd for C17H13BrN2O:
340.0211, found: 340.0212.
1
nol) (lit.[23] mp: 228–2298C); H NMR (400 MHz, CD3OD): d=6.02 (s,
2H), 7.59–7.69 (m, 4H), 8.09 (dd, J=8.8 and 2.4 Hz, 2H), 8.97 ppm
(s, 1H); 13C NMR (100 MHz, CD3OD): d=56.2, 120.6, 125.0, 130.5,
131.0, 133.8, 138.1, 141.9, 191.1 ppm; HRMS-ESI m/z [MÀCl]+ calcd
for C11H10ClN2O: 221.0482, found: 221.0472.
1-(3-Bromophenyl)-2-(1H-imidazol-1-yl)ethanone hydrochloride
(32·HCl): Method A afforded the product as a light-yellow solid
(480 mg, 53%); mp: 217–2188C (EtOH); 1H NMR (400 MHz,
[D6]DMSO): d=6.11 (s, 2H), 7.61 (t, J=8.0 Hz, 1H), 7.70 (t, J=
1.4 Hz, 1H), 7.73 (t, J=1.4 Hz, 1H), 7.97 (dd, J=8.0 and 1.2 Hz, 1H),
8.05 (d, J=8.0 Hz, 1H), 8.21 (t, J=1.2 Hz, 1H), 9.12 ppm (s, 1H);
13C NMR (100 MHz, [D6]DMSO): d=55.1, 119.4, 122.3, 123.4, 127.1,
130.6, 131.3, 135.8, 136.5, 136.9, 190.7 ppm; HRMS-ESI m/z [MÀCl]+
calcd for C11H10BrN2O: 264.9976, found: 264.9968.
1-[4-(Benzyl)phenyl]-2-(1H-imidazol-1-yl)ethanone hydrochloride
(38·HCl): Method B afforded the product as a light-tan solid
(554 mg, 59%); mp: 185–1868C (2-propanol); 1H NMR (400 MHz,
[D6]DMSO): d=4.07 (s, 2H), 6.06 (s, 2H), 7.18–7.34 (m, 5H), 7.49 (d,
J=8.4 Hz, 2H), 7.70 (t, J=1.6 Hz, 1H), 7.72 (t, J=1.6 Hz, 1H), 7.99
(d, J=8.4 Hz, 2H), 9.13 ppm (s, 1H); 13C NMR (100 MHz, [D6]DMSO):
d=40.9, 54.9, 119.2, 123.5, 126.2, 128.4, 128.5, 128.7, 129.3, 131.7,
136.5, 140.3, 148.4, 191.0 ppm; HRMS-ESI m/z [MÀCl]+ calcd for
C18H17N2O: 277.1335, found: 277.1330.
2-(1H-Imidazol-1-yl)-1-[4-(2-phenylethyl)phenyl]ethanone hydro-
chloride (39·HCl): Method B, using CH2Cl2 instead of EtOAc for the
extraction process, afforded the product as a white solid (627 mg,
1
64%); mp: 238–2408C (2-propanol); H NMR (400 MHz, [D6]DMSO):
1-(4-Bromophenyl)-2-(1H-imidazol-1-yl)ethanone hydrochloride
(33·HCl): Method B afforded the product as a white solid (398 mg,
44%); mp: 231–2338C (EtOH); 1H NMR (400 MHz, [D6]DMSO): d=
6.08 (s, 2H), 7.70 (t, J=1.4 Hz, 1H), 7.73 (t, J=1.4 Hz, 1H), 7.83–
7.90 (m, 2H), 7.95–8.03 (m, 2H), 9.12 ppm (s, 1H); 13C NMR
(100 MHz, [D6]DMSO): d=55.0, 119.4, 123.5, 128.6, 130.1, 132.2,
132.8, 136.6, 190.9 ppm; HRMS-ESI m/z [MÀCl]+ calcd for
C11H10BrN2O: 264.9976, found: 264.9968.
1-(4-Iodophenyl)-2-(1H-imidazol-1-yl)ethanone (34): Method B
produced, after the processing of the reaction mixture, a solid that
was extracted with boiling MeOH (50 mL). Evaporation of the sol-
vent and recrystallization of the residue from MeOH afforded the
product as a pale-pink solid (356 mg, 38%); mp: 214–2168C;
1H NMR (400 MHz, [D6]DMSO): d=5.70 (s, 2H), 6.94 (brs, 1H), 7.12
(brs, 1H), 7.59 (brs, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.99 ppm (d, J=
8.4 Hz, 2H); 13C NMR (100 MHz, [D6]DMSO): d=52.4, 102.4, 120.9,
127.8, 129.5, 133.8, 137.8, 193.2 ppm; HRMS-EI m/z [M]+ calcd for
C11H9IN2O: 311.9760, found: 311.9746.
d=2.90–2.98 (m, 2H), 2.98–3.06 (m, 2H), 6.01 (s, 2H), 7.15–7.31 (m,
5H), 7.46 (d, J=8.4 Hz, 2H), 7.68 (t, J=1.6 Hz, 1H), 7.72 (t, J=
1.6 Hz, 1H), 7.96 (d, J=8.4 Hz, 2H), 9.05 ppm (s, 1H); 13C NMR
(100 MHz, [D6]DMSO): d=36.4, 36.8, 54.9, 119.3, 123.5, 125.9, 128.2,
128.3, 128.4, 129.1, 131.6, 136.5, 140.9, 148.8, 191.0 ppm; HRMS-ESI
m/z [MÀCl]+ calcd for C19H19N2O: 291.1491, found: 291.1493.
1-[4-(Benzyloxy)phenyl]-2-(1H-imidazol-1-yl)ethanone (40): Meth-
od A gave a solid that was decolorized using charcoal and recrys-
tallized to afford the product as a pale-yellow solid (290 mg, 33%);
1
mp: 177–1788C (EtOH); H NMR (400 MHz, [D6]DMSO): d=5.25 (s,
2H), 5.67 (s, 2H), 6.91 (s, 1H), 7.10 (s, 1H), 7.19 (d, J=8.8 Hz, 2H),
7.32–7.50 (m, 5H), 7.58 (s, 1H), 8.01 ppm (d, J=8.8 Hz, 2H);
13C NMR (100 MHz, [D6]DMSO): d=52.2, 69.6, 115.0, 120.9, 127.5,
127.7, 127.8, 128.1, 128.5, 130.3, 136.4, 138.3, 162.7, 191.8 ppm;
HRMS-EI m/z [M]+ calcd for C18H16N2O2: 292.1212, found: 292.1212.
1-(4-Cyclohexylphenyl)-2-(1H-imidazol-1-yl)ethanone hydrochlo-
ride (41·HCl): Method B afforded the product as a white solid
(477 mg, 52%); mp: 242–2448C (2-propanol); 1H NMR (400 MHz,
[D6]DMSO): d=1.18–1.53 (m, 5H), 1.72 (d, J=12.4 Hz, 1H), 1.80 (d,
J=12.0 Hz, 4H), 2.61–2.69 (m, 1H), 6.07 (s, 2H), 7.48 (d, J=8.0 Hz,
2H), 7.71 (s, 1H), 7.73 (s, 1H), 7.98 (d, J=8.0 Hz, 2H), 9.14 ppm (s,
1H); 13C NMR (100 MHz, [D6]DMSO): d=25.4, 26.0, 33.4, 43.8, 54.8,
119.2, 123.4, 127.3, 128.3, 131.6, 136.5, 154.5, 190.9 ppm; HRMS-ESI
m/z [MÀCl]+ calcd for C17H21N2O: 269.1648, found: 269.1651.
2-(1H-Imidazol-1-yl)-1-(naphthalen-1-yl)ethanone hydrochloride
(42·HCl): Method A afforded the product as a white solid (376 mg,
46%); mp: 215–2168C (2-propanol/Et2O); 1H NMR (400 MHz,
[D6]DMSO): d=6.18 (s, 2H), 7.60–7.76 (m, 3H), 7.77 (s, 1H), 7.83 (s,
1H), 8.08 (d, J=7.6 Hz, 1H), 8.29 (d, J=8.0 Hz, 1H), 8.39 (d, J=
7.2 Hz, 1H), 8.65 (d, J=8.4 Hz, 1H), 9.25 ppm (s, 1H); 13C NMR
(100 MHz, [D6]DMSO): d=56.5, 119.3, 123.6, 124.8, 125.2, 126.6,
128.4, 128.7, 129.6 (2C), 130.9, 133.5, 134.2, 136.7, 194.3 ppm;
HRMS-ESI m/z [MÀCl]+ calcd for C15H13N2O: 237.1027, found:
237.1033.
2-(1H-Imidazol-1-yl)-1-(4-nitrophenyl)ethanone
hydrochloride
(35·HCl): Method A produced, after extraction with EtOAc, a dark-
red solid that was subjected to chromatography twice (silica gel,
EtOAc/MeOH 9:1) and finally recrystallized from 2-propanol to
afford the free base as a light-orange solid (243 mg, 35%). The hy-
drochloride was obtained in the usual manner in acetone as a
white solid (249 mg, 31% overall); mp: 243–2458C (2-propanol)
1
(lit.[26] mp: 211–2168C, dec.); H NMR (400 MHz, [D6]DMSO): d=6.20
(s, 2H), 7.73 (t, J=1.4 Hz, 1H), 7.76 (t, J=1.4 Hz, 1H), 8.30 (d, J=
8.8. Hz, 2H), 8.44 (d, J=8.8 Hz, 2H), 9.16 ppm (s, 1H); 13C NMR
(100 MHz, [D6]DMSO): d=55.4, 119.3, 123.5, 124.1, 129.6, 136.5,
138.4, 150.5, 191.0 ppm; HRMS-ESI m/z [MÀCl]+ calcd for
C11H10N3O3: 232.0722, found: 232.0719.
1-(Biphenyl-4-yl)-2-(1H-imidazol-1-yl)ethanone
hydrochloride
(36·HCl): Method B afforded the product as a white solid (412 mg,
46%); mp: 235–2378C (EtOH); 1H NMR (400 MHz, [D6]DMSO): d=
6.14 (s, 2H), 7.42–7.50 (m, 1H), 7.50–7.58 (m, 2H), 7.71–7.77 (m,
2H), 7.78–7.85 (m, 2H), 7.95 (d, J=8.8 Hz, 2H), 8.14 (d, J=8.8 Hz,
2-(1H-Imidazol-1-yl)-1-(naphthalen-2-yl)ethanone hydrochloride
(43·HCl):
A
mixture of 2-bromo-1-(naphthalen-1-yl)ethanone
1548
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ChemMedChem 2010, 5, 1541 – 1555