Organic & Biomolecular Chemistry
Paper
Notes and references
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Scheme 4 Proposed reaction mechanism.
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According to the above observations, the possible routes
might exist as shown in Scheme 4 based on the previous
reports in the literature.12 Firstly, ammonia is reacted with the
aldehyde to form an N-substituted imine, and the following
step is copper catalyzed with 2-iodoaniline to form the metallic
intermediates (IV). Then, the copper-catalyzed reaction of
N-substituted imine (I) with intermediates (IV) affords inter-
mediates (V), and the subsequent intramolecular nucleophilic
cyclization affords the final product.
Conclusions
In summary, we have developed an efficient and promising
three-component reaction of 2-haloaniline including aryl
iodides and bromides, various aldehydes, and ammonia to
form benzimidazoles in a simple one-pot procedure. In this
copper catalytic system, a new reaction mechanism was devel-
oped, and neat water was used as the solvent. The tolerance of
diverse functional groups makes the present system attractive.
To the best of our knowledge, this is the first example of using
ammonia as the nitrogen source in the synthesis of substituted
benzimidazoles in water. Considering the inexpensive catalytic
system and the readily available starting materials, this strategy
would thus be highly useful in the synthesis of biologically
important compounds containing a benzimidazole framework.
Conflicts of interest
5 (a) H. Sharghi, M. H. Beyzavi and M. M. Doroodmand,
Eur. J. Org. Chem., 2008, 4126–4138; (b) D. Yang, H. Fu,
L. Hu, Y. Jiang and Y. Zhao, J. Org. Chem., 2008, 73, 7841–
7844; (c) Y. Kim, M. T. Kumar, N. Park, Y. Heo and S. Lee,
J. Org. Chem., 2011, 76, 9577–9583; (d) E. Dezfoolinezhad,
K. Ghodrati and R. Badri, New J. Chem., 2016, 40, 4575–
4587; (e) G. Smitha and K. Sreekumar, RSC Adv., 2016, 6,
18141–18155; (f) F. Feng, J. Ye, Z. Cheng, X. Xu, Q. Zhang,
L. Ma, C. Lu and X. Li, RSC Adv., 2016, 6, 72750–72755.
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There are no conflicts to declare.
Acknowledgements
We are grateful for the financial support from the Research
Fund of Fujian Provincial Foundation (2016J01686,
2016J01372, 2016Y9051, 2017J01820). We also thank the
Analytic and Testing Centre of Sichuan University for the NMR
spectral measurement.
This journal is © The Royal Society of Chemistry 2018
Org. Biomol. Chem., 2018, 16, 8090–8094 | 8093