January 2010 A Simple, Mild, and Efficient Procedure for High-Yield Synthesis of Benzimidazoles
Using Coppertriflate as Catalyst
155
ꢁ
1
1
hindered aldehyde 2-naphthaldehyde (3l). Substituted
aldehydes have been used with similar success to pro-
vide the corresponding benzimidazoles in high yields,
which are also of much interest with regard to biological
activity. The reaction conditions are mild and the exper-
imental procedure is simple. The products were formed
in high yields (74–95%). The structures of the products
Compound (3e). IR (KBr): m 3189, 2980, 1625 cm
;
H
NMR (CDCl þ DMSO-d ): d 12.70 (1H, br s), 8.07 (2H, d, J
3
6
¼
8.0 Hz), 7.57 (1H, m), 7.26–7.22 (3H, m), 7.19–7.06 (2H,
37
þ
35
þ
m); FABMS: m/z 231 ( Cl [MþH] ), 229 ( Cl [MþH] );
9 2
Anal. Calcd for C13H N Cl: C, 68.27; H, 3.94; N, 12.25.
Found: C, 68.42; H, 3.86; N, 12.38.
Compound (3l). IR (KBr): m 3055, 2925, 2853, 1624 cm
ꢁ1
;
1
H NMR (CDCl þ DMSO-d ): d 11.86 (1H, br s), 8.75 (1H,
3
6
1
were determined from their spectral ( H NMR, IR, and
br s), 8.39 (1H, dd, J ¼ 8.0, 2.0 Hz), 8.02–7.90 (3H, m),
7
[
1
.69–7.52 (4H, m), 7.26–7.18 (2H, m); FABMS: m/z 245
MS) data. Several examples illustrating this novel and
general method for the synthesis of benzimidazoles are
summarized in Table 1.
þ
MþH] ; Anal. Calcd for C17
12 2
H N : C, 83.61; H, 4.92; N,
1.47. Found: C, 83.87; H, 4.88; N, 11.61.
CONCLUSIONS
In summary, we have developed a new methodology
for the synthesis of various benzimidazoles by using
REFERENCES AND NOTES
[
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presence of copper triflate catalyst at reflux temperature.
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available methods.
[
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1
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EXPERIMENTAL
General procedure for the synthesis of benzimidazoles. To
a mixture of an aldehyde (0.5 mmol) and 1,2-phenylenedi-
amine (0.6 mmol) in acetonitrile (5 mL) under a nitrogen
atmosphere, coppertriflate (0.5 mmol) was added. The mixture
was stirred at reflux temperature, and the reaction was moni-
tored by TLC. After completion, the solvent was evaporated
and the mixture was extracted with EtOAc (3 ꢀ 10 mL). The
extract was concentrated, and the crude product was purified
by silica gel column chromatography using ethyl acetate–n-
hexane (1:9) as eluent to afford the desired product 3. The res-
idue was subjected to column chromatography (silica gel, hex-
[
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(
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[
[
4] Lin, S.; Yang, L. Tetrahedron Lett 2005, 46, 4315.
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ane–EtOAc) to obtain the pure benzimidazole. The spectral
1
( H NMR, IR, and MS) data of some representative benzimi-
dazoles are given below.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet