In another method, benzimidazoles have been prepared by
classical cyclocondensation of 1,2-phenylendiamines with the
corresponding aldehydes under oxidative conditions.8–13
While many reports are available for the preparation of
2-substituted benzothiazoles,14 the most popular approaches
generally involve condensation-dehydration of 2-aminothiophe-
nol with carboxylic acids15 or condensation with aldehydes
under oxidative conditions.16
Unfortunately, many of these processes suffer limitations,
such as drastic reaction conditions, low yields, tedious workup
procedures, and co-occurrence of several side reactions. As a
consequence, the introduction of new methods and/or further
work on technical improvements to overcome the limitations
is still an important experimental challenge.
Mild and Highly Efficient Method for the
Synthesis of 2-Arylbenzimidazoles and
2-Arylbenzothiazoles
Kiumars Bahrami,*,† M. Mehdi Khodaei,* and Fardin Naali
Department of Chemistry, Razi UniVersity, Kermanshah
67149, Iran, and Nanoscience and Nanotechnology Research
Center (NNRC), Razi UniVersity, Kermanshah 67149, Iran
kbahrami2@hotmail.com; mmkhoda@razi.ac.ir
ReceiVed May 15, 2008
Diluted solutions of hydrogen peroxide are a universal,
ecologically clean, and convenient way to handle reagents for
different oxidations in the liquid phase.17–19 Developing envi-
ronmentally benign technologies that provide economical
synthetic strategies is an area of research that is being vigorously
pursued. Much of this impact is associated with solvent waste.
The toxic and/or hazardous properties of many solvents in
conjunction with crucial environmental concerns, such as
atmospheric emissions and contamination of water effluents, is
restricting their use.20 Solvent-free reactions have many advan-
tages: reduced pollution, low cost, and simplicity in process
and handling.
A new, convenient method for the syntheses of 2-substituted
benzimidazole and benzothizole is described. Short reaction
times, large-scale synthesis, easy and quick isolation of the
products, excellent chemoselectivity, and excellent yields are
the main advantages of this procedure.
In continuation of our work21 on the development of useful
synthetic methodologies, in this study we wish to report the
use of a catalytic redox cycling for the synthesis of various
benzimidazole derivatives, based on (Ce(IV)/Ce(III))-redox-
mediated oxidation of the Schiff’s base intermediates derived
from differently substituted aromatic 1,2-phenylendiamines and
a variety of aromatic aldehydes (Scheme 1).
Ceric ammonium nitrate (CAN), a very inexpensive and easily
available oxidizing agent, has been widely used in organic
reactions,22 but it has not been carefully studied as a catalyst in
Compounds that exhibit the functionality of benzimidazole
and benzothiazole have been extensively employed in the area
of pharmaceuticals.1–4 The high profile of biological applications
of compounds with benzimidazole and benzothiazole structures
has prompted extensive studies for their synthesis.
Methods of benzimidazole synthesis include the condensation
of 1,2-phenylendiamines with carboxylic acids or their deriva-
tives in the presence of strong acids such as polyphosphoric
acid5 or mineral acids6 and the thermal or acid-promoted
cyclization of N-(N-arylbenzimidoyl)-1,4-benzoquinoneimines.7
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* To whom correspondence should be addressed. Fax: +98(831)4274559.
† Department of Chemistry.
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J. F.; Hlasta, D. J. Bioorg. Med. Chem. Lett. 2001, 11, 1545.
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10.1021/jo8010232 CCC: $40.75
Published on Web 07/25/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6835–6837 6835