Chemical Papers
ORIGINAL PAPER
Synthesis of 1H‑1,3‑benzimidazoles, benzothiazoles
and 3H‑imidazo[4,5‑c]pyridine using DMF in the presence of HMDS
as a reagent under the transition‑metal‑free condition
Hamid Mostafavi1,2 · Mohammad Reza Islami1 · Ehsan Ghonchepour · Ahmad Momeni Tikdari
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Received: 8 March 2018 / Accepted: 16 June 2018
©
Institute of Chemistry, Slovak Academy of Sciences 2018
Abstract
An operationally simple method for synthesis of benzimidazole and 3H-imidazo[4,5-c]pyridine from o-phenylenediamine
or pyridine-3, 4-diamine and N,N-dimethylformamide (DMF) in the presence of hexamethyldisilazane (HMDS) as a reagent
is described. To evaluate the scope of application of this reagent, it was also used to prepare benzothiazole, 1H-perimidine,
and benzoxazole, which was successful for benzothiazole and 1H-perimidine but benzoxazole was not formed. This reac-
tion complies with the principles of green chemistry as it does not use toxic solvents, transition metals, or strong acids. The
products are obtained in moderate to excellent yields.
Keywords Benzimidazole · Heterocyclic compounds · HMDS · DMF · Biological activities
Introduction
benzimidazole ring causes to exhibit a wide range of phar-
macological activities (Maryanoꢂ et al. 1995).
Benzimidazole is a bicyclic heteroaromatic compound con-
taining an imidazole ring, where a benzene ring fused to the
Today, diꢂerent strategies are used to synthesize organic
compounds (Yang et al. 2004, 2017). With regard to the
application of benzimidazole and its derivatives in chemis-
try and pharmacy, various methods have been used for the
synthesis of benzimidazole such as, reaction of 1,2-arylen-
ediamines with aldehydes, ketones, acid anhydrides, acid
chlorides, esters, amides, nitriles, urea, in the presence of
a catalyst such as In(OTF) (Trivedi et al. 2006), Na AlF
4
- and 5-position of the imidazole ring. The imidazole is an
important heterocyclic compound that is found in several
natural compounds such as purine, vitamins (B ), some of
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the amino acids same as histidine. This compound shows a
vital role in the metabolism of all living cells. Benzimida-
zole derivatives exhibit numerous signiꢀcant medical and
biological activities such as antiallergic (Nakano et al. 1999),
anticancer (Tong et al. 2009), antibacterial (Menteşe et al.
3
3
6
(Grigorjeva et al. 2014), Zn(OTF) (Srinivasulu et al. 2014),
2
Na S O (Alaqeel 2017), CdCl (Sammaiah et al. 2012),
2
2
5
2
2
2
014), antiulcer (Iwahi et al. 1991), antifungal (Ke et al.
014), antihistaminic (Iemura et al. 1987), antiviral (Tonelli
NH OAc (Sharghi et al. 2008a), BF -etherate (Nagawade
4
3
and Shinde 2006), Au-CeO (Ruiz et al. 2010), NaHSO
2
3
et al. 2014), anti-inꢁammatory (Sondhi et al. 2006), anti-
depressant (Siddiqui et al. 2011), and antidiabetic (Bansal
and Silakari 2012) (Fig. 1). The literature survey reveals
that the presence of a substitution at 1, 2 and 5 positions of
(Austen and Kane 2001), MnO (Bhatnagar and George
2
1968), copper complex (Sharghi et al. 2008c), ceric ammo-
nium nitrate (CAN) (Kidwai et al. 2010), K [Fe(CN) ]
4
6
(Shaikh and Patil 2012), zinc chloride (Mahajan et al.
2
2
013), silica boron sulfonic acid (SBSA) (Sajjadifar et al.
012), lanthanum chloride (Venkateswarlu et al. 2013),
TsOH/graphite (Sharghi et al. 2008b), and hydrogen per-
oxide (Gadekar et al. 2010). Some of these methods suf-
fer from disadvantages such as environmental damage, the
use of strong acids, high temperatures, and use of toxic
metal catalysts and hazardous reagents that is in conꢁict
with green chemistry. Therefore, a research for new reagent
and the development of new methods are still of practical
*
Mohammad Reza Islami
1
2
Chemistry Department, Shahid Bahonar University
of Kerman, Kerman 76169, Iran
Kerman Agricultural and Natural Resource Research
and Education Center, (AREEO), Kerman, Iran
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