yellow oil: 1H NMR (400 MHz, CDCl3) d 7.28 (m, 2H), 7.17 (m,
3H), 5.10 (dd, J = 4.4, 10.0 Hz, 1H), 2.61 (m, 4H), 1.63 (m, 6H),
1.35 (m, 6H) 0.92 (t, J = 6.8 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3) d 199.5, 142.5, 128.6, 128.5, 126.0, 94.5, 39.5, 35.9, 31.3,
29.6, 28.7, 28.1, 23.3, 22.2, 13.9 ppm; IR nmax/cm-1 3027, 2931,
2859, 1731, 1559, 1454, 1363, 1030, 748, 700; HRMS (FAB) calcd
for C17H25NO3 (MNa+) 314.1727, found 314.1722.
128.1, 125.5, 121.9, 117.5, 35.5, 31.1, 28.6, 28.1, 22.9, 7.5 ppm; IR
n
max/cm-1 3169, 2929, 2857, 1680, 1453, 1020, 749, 700; HRMS
(FAB) calcd for C15H21N3 (MH+) 244.1808, found 244.1814.
5-Ethyl-4-(5-phenylpentyl)-1H-imidazol-2-amine
(12). 3-
Nitro-9-phenylnonan-4-one (0.050 g, 0.19 mmol) reacted with
concentrated HCl (0.95 mmol) and palladium, 5 wt.% on
activated carbon (0.081 g, 0.038 mmol) under H2, then reacted
with cyanamide (0.040 g, 0.95 mmol) according to the general
procedure. Purification by column chromatography gave 0.014 g
(29%) over two steps as a yellow oil: 1H NMR (300 MHz,
CD3OD) d 7.25 (m, 2H), 7.14 (m, 3H), 2.59 (t, J = 7.5 Hz, 2H),
2.42 (m, 4H), 1.63 (m, 4H), 1.28 (m, 2H), 1.13 (t, J = 7.5 Hz, 3H)
ppm; 13C NMR (75 MHz, CD3OD) d 146.2, 142.4, 128.2, 128.1,
125.5, 123.6, 121.3, 35.5, 31.1, 28.7, 28.1, 22.9, 16.5, 13.1 ppm; IR
7-Nitro-1-phenyldodecan-6-one. 6-Phenylhexanoic
acid
(0.150 g, 0.78 mmol) and CDI (0.253 g, 1.56 mmol) were added
together and then reacted with nitrohexane (0.153 g, 1.17 mmol)
and DBU (0.297 g, 1.95 mmol) according to the general procedure.
Purification by column chromatography gave 0.090 g (38%) as a
yellow oil: 1H NMR (400 MHz, CDCl3) d 7.28 (m, 2H), 7.17 (m,
3H), 5.11 (dd, J = 4.8, 10.4 Hz, 1H), 2.61 (m, 4H), 1.63 (m, 6H),
1.33 (m, 8H) 0.90 (t, J = 6.8 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3) d 199.5, 142.5, 128.6, 128.5, 126.0, 94.6, 39.5, 35.9, 31.3,
31.2, 29.9, 28.7, 25.7, 23.3, 22.4, 14.1 ppm; IR nmax/cm-1 3027,
2930, 2858, 1731, 1559, 1454, 1363, 1030, 748, 699; HRMS (FAB)
calcd for C18H27NO3 (MNa+) 328.1883, found 328.1881.
n
max/cm-1 3327, 2934, 1680, 1453, 1016, 749; HRMS (FAB) calcd
for C16H23N3 (MH+) 258.1965, found 258.1973.
4-(5-Phenylpentyl)-5-propyl-1H-imidazol-2-amine
(13). 4-
Nitro-10-phenyldecan-5-one (0.084 g, 0.30 mmol) reacted with
concentrated HCl (1.50 mmol) and palladium, 5 wt.% on
activated carbon (0.129 g, 0.060 mmol) under H2, then reacted
with cyanamide (0.064 g, 1.50 mmol) according to the general
procedure. Purification by column chromatography gave 0.025 g
(30%) over two steps as a yellow oil: 1H NMR (300 MHz,
CD3OD) d 7.20 (m, 2H), 7.15 (m, 3H), 2.60 (t, J = 7.2 Hz,
2H), 2.40 (m, 4H), 1.56 (m, 6H), 1.30 (m, 2H), 0.92 (t, J =
7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CD3OD) d 146.4, 142.5,
128.3, 128.1, 125.6, 122.1, 121.9, 35.5, 31.1, 28.8, 28.2, 25.0, 23.0,
22.3, 12.6 ppm; IR nmax/cm-1 3165, 2931, 1680, 1453, 1031, 747,
699; HRMS (FAB) calcd for C17H25N3 (MH+) 272.2121, found
272.2127.
7-Nitro-1-phenyltridecan-6-one. 6-Phenylhexanoic
acid
(0.150 g, 0.78 mmol) and CDI (0.253 g, 1.56 mmol) were added
together and then reacted with nitroheptane (0.170 g, 1.17 mmol)
and DBU (0.297 g, 1.95 mmol) according to the general procedure.
Purification by column chromatography gave 0.104 g (42%) as a
yellow oil: 1H NMR (400 MHz, CDCl3) d 7.28 (m, 2H), 7.17 (m,
3H), 5.11 (dd, J = 4.8, 10.0 Hz, 1H), 2.61 (m, 4H), 1.63 (m, 6H),
1.33 (m, 10H) 0.89 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3) d 199.5, 142.5, 128.6, 128.5, 126.0, 94.6, 39.4, 35.9, 31.5,
31.3, 29.9, 28.8, 28.7, 26.0, 23.3, 22.7, 14.2 ppm; IR nmax/cm-1
3027, 2931, 2859, 1731, 1559, 1454, 1363, 1031, 748, 700; HRMS
(FAB) calcd for C19H29NO3 (MNa+) 342.2040, found 342.2038.
5-Butyl-4-(5-phenylpentyl)-1H-imidazol-2-amine
(14). 7-
General procedure for 2-aminoimidazole synthesis
Nitro-1-phenylundecan-6-one (0.049 g, 0.17 mmol) reacted
with concentrated HCl (0.85 mmol) and palladium, 5 wt.% on
activated carbon (0.072 g, 0.034 mmol) under H2, then reacted
with cyanamide (0.035 g, 0.84 mmol) according to the general
procedure. Purification by column chromatography gave 0.025 g
(52%) over two steps as a yellow oil: 1H NMR (400 MHz,
CD3OD) d 7.22 (m, 2H), 7.15 (m, 3H), 2.60 (t, J = 7.2 Hz, 2H),
2.43 (m, 4H), 1.64 (m, 6H), 1.34 (m, 4H), 0.94 (t, J = 7.6 Hz, 3H)
ppm; 13C NMR (75 MHz, CD3OD) d 146.4, 142.4, 128.2, 128.1,
125.6, 122.1, 121.9, 35.5, 31.2, 31.1, 28.7, 28.2, 23.0, 22.8, 21.9,
12.9 ppm; IR nmax/cm-1 3166, 2930, 2857, 1680, 1453, 1030, 748,
699; HRMS (FAB) calcd for C18H27N3 (MH+) 286.2278, found
286.2288.
The appropriate a-nitro ketone (>85% pure, judged by 1H NMR)
was dissolved in ethanol (3 mL), concentrated HCl and 5%
palladium on carbon (0.2 equivalents) were added and the reaction
was stirred under H2 for 24 h. The mixture was filtered through
Celite and the solvent was evaporated under reduced pressure. The
residue was dissolved in ethanol (3 mL) and the pH was adjusted
to 4.5 with 0.1 N NaOH. To the solution was added cyanamide
and heated at 95 ◦C for 2 h. The ethanol was then evaporated
under reduced pressure and the resulting residue was purified
by column chromatography (CH2Cl2–MeOH sat. NH3 80 : 20) to
afford the desired compound in its free base form. Addition of
concentrated HCl to a methanol solution (2 mL) of the free base
followed by solvent evaporation under reduced pressure delivered
the corresponding 2-aminoimidazole as its HCl salt.
5-Pentyl-4-(5-phenylpentyl)-1H-imidazol-2-amine
(15). 7-
Nitro-1-phenyldodecan-6-one (0.090 g, 0.29 mmol) reacted
with concentrated HCl (1.45 mmol) and palladium, 5 wt.% on
activated carbon (0.125 g, 0.060 mmol) under H2, then reacted
with cyanamide (0.062 g, 1.47 mmol) according to the general
procedure. Purification by column chromatography gave 0.071 g
(81%) over two steps as a yellow oil: 1H NMR (300 MHz,
CD3OD) d 7.20 (m, 2H), 7.14 (m, 3H), 2.59 (t, J = 7.5 Hz, 2H),
2.42 (m, 4H), 1.56 (m, 6H), 1.32 (m, 6H), 0.90 (t, J = 7.2 Hz,
3H) ppm; 13C NMR (75 MHz, CD3OD) d 146.3, 142.5, 128.3,
128.1, 125.6, 122.1, 121.8, 35.5, 31.1, 31.1, 28.7, 28.7, 28.2, 23.1,
23.0, 22.3, 13.3 ppm; IR nmax/cm-1 3169, 2928, 2857, 1680, 1453,
5-Methyl-4-(5-phenylpentyl)-1H-imidazol-2-amine
(11). 2-
Nitro-8-phenyloctan-3-one (0.025 g, 0.10 mmol) reacted with
concentrated HCl (0.50 mmol) and palladium, 5 wt.% on
activated carbon (0.043 g, 0.020 mmol) under H2, then reacted
with cyanamide (0.021 g, 0.50 mmol) according to the general
procedure. Purification by column chromatography gave 0.010 g
(41%) over two steps as a yellow oil: 1H NMR (300 MHz,
CD3OD) d 7.22 (m, 2H), 7.14 (m, 3H), 2.59 (t, J = 7.5 Hz, 2H),
2.42 (t, J = 6.9 Hz, 2H), 2.01 (s, 3H) 1.60 (m, 4H), 1.31 (m,
2H) ppm; 13C NMR (75 MHz, CD3OD) d 146.2, 142.5, 128.3,
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The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 2814–2822 | 2819
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