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DOI: 10.1055/s-0030-1259007
Mild and General One-Pot Reduction and Cyclization of Aromatic and Heteroaromatic 2-Nitroamines to Bicyclic 2H-Imidazoles
Publication History
Publication Date:
14 October 2010 (online)

Abstract
A one-pot procedure for the conversion of aromatic and heteroaromatic 2-nitroamines into bicyclic 2H-benzimidazoles is described. The procedure employs formic acid, iron powder, and an additive such as NH4Cl to reduce the nitro group and effect the imidazole cyclization with high-yielding conversions generally within one to two hours. The compatibility with a wide range of functionality demonstrates the general utility of this procedure.
Key words
cyclization - heterocycles - imidazole - iron - reduction
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References and Notes
The role of the alcohol co-solvent in this reaction is to increase solubilization of the substrate and may be omitted for substrates with good solubility in neat formic acid (unpublished observation).
9If the reaction is followed by LC-MS at shorter time intervals, the progression from starting material to bisaniline to N-formylated aniline to cyclized product can typically be observed.
10
Analytical Data
for Compounds 2-19
1-Ethyl-1
H
-benzo[
d
]imidazole
¹6
(2)
ESI-MS: m/z = 147.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 8.23
(s, 1 H), 7.62 (dd, J = 18.0,
7.9 Hz, 2 H), 7.22 (dt, J = 15.0,
7.2 Hz, 2 H), 4.28 (q, J = 7.3
Hz, 2 H), 1.41 (t, J = 7.3
Hz, 3 H).
1-Phenyl-1
H
-benzo[
d
]imidazole
¹7
(3)
ESI-MS: m/z = 195.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 8.56
(s, 1 H), 7.78 (dd, J = 6.5,
2.3 Hz, 1 H), 7.69 (dd, J = 8.4,
1.1 Hz, 2 H), 7.67-7.60 (m, 3 H), 7.51 (t, J = 7.2 Hz,
1 H), 7.38-7.28 (m, 2 H).
N
,
N
-Dimethyl-1
H
-benzo[
d
]imidazol-6-amine (4)
ESI-MS: m/z = 162.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.0
(br s, 1 H), 7.96 (s, 1 H), 7.40 (br s, 1 H), 6.78 (d, J = 7.9 Hz,
2 H), 2.88 (s, 6 H).
5-Ethoxy-1
H
-benzo[
d
]imidazole
¹8
(5)
ESI-MS: m/z = 163.0 [M + H]+. ¹H
NMR (400 MHz, DMSO, reported as a mixture of tautomers): δ = 12.25
(br s, 0.4 H), 12.20 (br s, 0.6 H), 8.10 (br s, 0.4 H), 8.04 (br
s, 0.6 H), 7.49 (br d, J = 8.8
Hz, 0.6 H), 7.38 (br d, J = 8.2
Hz, 0.4 H), 7.14 (br s, 0.4 H), 6.98 (br s, 0.6 H), 6.83-6.77
(m, 1 H), 4.03 (q, J = 6.9
Hz, 2 H), 1.34 (t, J = 6.9
Hz, 3 H).
1
H
-Benzo[
d
]imidazole-5-carbonitrile
¹9
(6)
ESI-MS: m/z = 144.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.96
(s, 1 H), 8.47 (s, 1 H), 8.16 (s, 1 H), 7.76 (d, J = 8.0
Hz, 1 H), 7.59 (d, J = 8.1
Hz, 1 H).
5-Chloro-1
H
-benzo[
d
]imidazole
²0
(7)
ESI-MS: m/z = 152.9 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.60
(s, 1 H), 8.27 (s, 1 H), 7.62 (m, 2 H), 7.22 (d, J = 7.7
Hz, 1 H).
4-Chloro-1
H
-benzo[
d
]imidazole
²¹
(8)
ESI-MS: m/z = 153.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 8.31
(s, 1 H), 7.55 (d, J = 7.9
Hz, 1 H), 7.30-7.05 (m, 2 H).
5-Iodo-1
H
-benzo[
d
]imidazole
²²
(9)
ESI-MS: m/z = 244.9 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.52
(br s, 1 H), 8.19 (s, 1 H), 7.95 (s, 1 H), 7.47 (dd, J = 8.4, 1.4
Hz, 1 H), 7.43 (d, J = 8.4
Hz, 1 H).
Methyl 1
H
-Benzo[
d
]imidazole-7-carboxylate
²³
(10)
ESI-MS: m/z = 177.3 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.56
(s, 1 H), 8.31 (s, 1 H), 7.97 (d, J = 8.0
Hz, 1 H), 7.86 (d, J = 7.6
Hz, 1 H), 7.32 (t, J = 7.8
Hz, 1 H), 3.95 (s, 3 H).
1
H
-Benzo[
d
]imidazol-5-ol
²4
(11)
ESI-MS: m/z = 135.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.21
(br s, 1 H), 9.08 (s, 1 H), 8.03 (s, 1 H), 7.37 (d, J = 8.6 Hz,
1 H), 6.87 (s, 1 H), 6.68 (d, J = 8.5
Hz, 1 H).
5-(Allyloxy)-1
H
-benzo[
d
]imidazole
(12)
ESI-MS: m/z = 175.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.25
(s, 1 H), 8.08 (s, 1 H), 7.45 (s, 1 H), 7.08 (s, 1 H), 6.83 (dd, J = 8.7, 2.0
Hz, 1 H), 6.07 (ddt, J = 17.2, 10.5,
5.2 Hz, 1 H), 5.41 (ddd, J = 17.3,
3.4, 1.6 Hz, 1 H), 5.26 (dd, J = 10.5,
1.5 Hz, 1 H), 4.61-4.54 (m, 2 H).
5-(Triisopropylsilyloxy)-1
H
-benzo[
d
]imidazole
(13)
ESI-MS: m/z = 291.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.17
(s, 1 H), 8.09 (s, 1 H), 7.43 (s, 1 H), 6.99 (s, 1 H), 6.76 (d, J = 8.9 Hz,
1 H), 1.25 (dd, J = 14.9,
7.2 Hz, 3 H), 1.07 (d, J = 7.4
Hz, 18 H).
5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1
H
-benzo[
d
]imidazole
(14)
ESI-MS: m/z = 245.4 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.48
(s, 1 H), 8.24 (s, 1 H), 7.90 (s, 1 H), 7.57 (s, 1 H), 7.50 (d,
1 H), 1.31 (s, 12 H).
3
H
-Imidazo[4,5-
f
]quinoline
²5
(15)
ESI-MS: m/z = 169.9 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 13.51
(br s, 0.5 H), 12.94 (br s, 0.5 H), 8.86-8.85 (m, 1 H),
8.78 (br s, 1 H), 8.38 (br s, 1 H), 7.97 (br d, J = 7.8
Hz, 1 H), 7.81 (d, J = 8.9
Hz, 1 H), 7.61 (dd, J = 8.3, 4.3
Hz, 1 H).
3-{1
H
-Benzo[
d
]imidazol-5-yl}-3
H
-imidazo[4,5-
b
]pyridine
(16)
ESI-MS: m/z = 250.2 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 12.72
(s, 1 H), 8.83 (s, 1 H), 8.36 (s, 1 H), 8.28 (s, 1 H), 8.13 (s,
1 H), 8.02 (s, 1 H), 7.85-7.60 (m, 2 H), 2.46 (s, 3 H).
6-Bromo-7-methyl-3
H
-imidazo[4,5-
b
]pyridine
²6
(17)
ESI-MS: m/z = 211.9 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 8.42
(s, 1 H), 8.40 (s, 1 H), 2.60 (s, 3 H).
6-Phenyl-1
H
-imidazo[4,5-
c
]pyridine
(18)
ESI-MS: m/z = 196.3 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 9.00
(s, 1 H), 8.40 (s, 1 H), 8.16-8.06 (m, 3 H), 7.53-7.43
(m, 2 H), 7.43-7.34 (m, 1 H).
6-Chloro-1
H
-imidazo[4,5-
c
]pyridine
²7
(19)
ESI-MS: m/z = 153.8 [M + H]+. ¹H
NMR (400 MHz, DMSO): δ = 8.74
(s, 1 H), 8.45 (s, 1 H), 7.67 (s, 1 H).