Synthesis of Benzimidazole Using Boric Acid

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ISSN: 0973-4945; CODEN ECJHAO E-Journal of Chemistry 2012, 9(1), 167-170
An Efficient and Inexpensive Synthesis of 2-Substituted Benzimidazoles in Water Using Boric Acid at Room Temperature
ZAHED KARIMI-JABERI and MOHAMMAD AMIRI Department of Chemistry, Firoozabad Branch Islamic Azad University, Firoozabad, Fars, Iran
[email protected] Received 13 June 2011; Accepted 13 August 2011 Abstract: 2-Substituted benzimidazoles have been synthesized in a one-pot reaction from o-phenylenediamine and aldehydes in the presence of boric acid in water at room temperature. The method was proved to be eco-friendly, convenient and the products were isolated with good yields. Keywords: Benzimidazoles, Boric acid, o-Phenylenediamine, Inexpensive synthesis
Introduction
The preparation of benzimidazoles has gained considerable attention in recent years. The benzimidazole is found in a variety of naturally occurring compounds and is of significant importance in medicinal chemistry. Their diverse applications include as potential antitumor agents1, antimicrobial agents2, angiotensin II inhibitors3, inhibitors of HCMV replication4, selective neuropeptide YY1 receptor antagonists5. In addition, benzimidazoles are very important intermediates in organic reactions6. Several methods have been reported for the synthesis of benzimidazoles7. The traditional synthesis of benzimidazole involves the reaction between o-phenylenediamine and a carboxylic acid or their derivatives at elevated temperature in the presence of strong acids such as polyphosphoric acid8 or mineral acids9 and thermal or acid promoted cyclization of N-(N-arylbenzimidoyl)-1,4-benzoquinoneimines10. Recently direct condensation of o-aryldiamines and aldehydes is the most convenient method for the preparation of these compounds. In this context some methods and catalysts have been reported such as indium triflate11, iodine12, cetylpyridinium bromide13, PEG 40014, (bromodimethyl)sulfonium bromide15 and ammonium acetate16. Although, these approaches are satisfactory for synthesis of benzimidazoles, the harsh reaction conditions, expensive reagents, use of toxic organic solvents and long reaction times limit the use of these methods.
168
ZAHED KARIMI-JABERI et al.
In recent years, water-mediated organic synthesis without using organic solvents has become one of the most important aspects in organic chemistry in order to meet the environmental demands. Carrying out organic synthesis in aqueous phase is highly challenging both from the synthetic view point and also from the impact of the environmental pollution17. During the course of our systematic studies directed towards the development of environmentally friendly procedures for several important organic transformations18-20, we now describe a simple, general and efficient protocol for the synthesis of 2-substituted benzimidazoles using boric acid in water at room temperature (Scheme 1).
NH2 O H N Boric acid R H H2O, r.t. N R
+
NH2
Scheme 1 Boric acid (H3BO3) is a useful and environmentally benign catalyst which has been successfully utilized in numerous reactions, for example, the aza Michael addition21, Biginelli reaction22 transesterification of ethyl acetoacetate23, mannich reaction24 and synthesis of aminophosphonates and dibenzoxanthenes by our group25-26. It offers milder conditions relative to common mineral acids. Boric acid is a readily available and inexpensive reagent and can conveniently be handled and removed from the reaction mixture. Thus, the remarkable catalytic activities together with its operational simplicity make it the most suitable catalyst for the reaction of diamines with aldehydes.
Experimental
A mixture of aldehyde (2 mmol), o-phenylenediamine (2 mmol), boric acid (0.1 g) and water (1 mL) was stirred at room temperature for the appropriate time indicated in Table 1. The progress of reactions was monitored by TLC (ethyl acetate/petroleum ether=1/4). After completion of the reaction, water (5 mL) was added and the mixture was stirred for 10 min. The obtained solid was collected by filtration and purified by recrystallization from ethanol. Spectral data for selected products: Entry 4: mp 291-293 C; 1HNMR (250 MHz, DMSO-d6): 12.98 (1H, br s), 8.17, (2H, d, J = 8.5 Hz), 7.53-7.63 (4H, m), 7.19-7.21 (2H, m).
Results and Discussion

To optimize the reaction conditions, the reaction of o-phenylenediamine with benzaldehyde was used as a model reaction. Reactions at different conditions in the presence of boric acid revealed that the best conditions were using water as solvent at room temperature. After completion of the reaction, the catalyst (boric acid) can easily be separated from the reaction mixture by washing the product with water. To show the generality of this method the optimized system was used for the synthesis of other derivatives. Several examples illustrating this novel and general method for the synthesis of dibenzoxanthenes are summarized in Table 1. These data clearly show that different aromatic aldehydes were successfully converted into the corresponding benzimidazoles in high yields at room temperature. The presence of electron-withdrawing or electron-donating substituents on the aromatic ring makes no difference to the course of the reaction. Various functionalities present in the aryl aldehydes, such as halogen, methoxy and nitro groups were tolerated (Table 1). Furthermore, unsaturated aldehydes, such as cinnamaldehydes (Entry 9), gave the corresponding benzimidazoles without any polymerization or conjugate addition to the ,-unsaturated carbonyl group under the above reaction conditions. Moreover, heteroaromatic (Entries 10-12)
An Efficient and Inexpensive Synthesis
169
were effective substrates to successfully execute couplings by boric acid. All products are known compounds and structures of them were confirmed by comparison with their known physical and spectral (NMR and IR) data1116. Table 1. Synthesis of 2-substituted benzimidazoles in the presence of boric acid Entry 1
CHO
Aldehyde
CHO
Product
H N N
Time, min 30
OMe
Yield, %a 92 90 91 93 90
2
MeO
H N N
15 20 15 15
CHO
3
H3 C
H N CH3 N H N
Cl N
CHO
4
Cl
CHO
5
O 2N
O2 N CHO
H N NO2 N
6
CHO
H N N
H N N
NO2
15
Cl Cl
92
7
Cl Cl
CHO
30 15 20
84 92 95 70 70 93
8
Me2 N
H N NMe2 N
9 10 11 12
Ph
CHO
H N N Ph
CHO
H N N S
35 15
N
CHO N
CHO N
CHO
H N N
H N N N
30
13
CHO
H N N
H N N H N
25
75
14
OHC
15
N
a
98b
Isolated yield, bconditions: o-phenylenediamine (2 mmol) terphthaldehyde (1 mmol)
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Conclusion
In conclusion this paper describes a convenient and efficient process for the synthesis of 2-substitued benzimidazoles by one-pot reaction of o-phenylenediamine with aldehydes in the presence of boric acid in water. This method offers some advantages in terms of simplicity of performance, using water as solvent, low reaction times, low cost and it follows along the line of green chemistry. The catalyst is readily available and inexpensive and can conveniently be handled and removed from the reaction mixture. We believe that this procedure is convenient, economic and a user-friendly process for the synthesis of substituted imidazoles of biological and medicinal importance.
References
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http://www.e-journals.

ISSN: 0973-4945; CODEN ECJHAO E-Journal of Chemistry 2012, 9(1), 167-170

ZAHED KARIMI-JABERI et al.

Results and Discussion

An Efficient and Inexpensive Synthesis

Isolated yield, bconditions: o-phenylenediamine (2 mmol) terphthaldehyde (1 mmol)

ZAHED KARIMI-JABERI et al.

Analytical Methods in Chemistry

The Scientific World Journal

Bioinorganic Chemistry and Applications

Submit your manuscripts at http://www.hindawi.com

Hindawi Publishing Corporation http://www.hindawi.com

Hindawi Publishing Corporation http://www.hindawi.com

Chromatography Research International

ISRN Inorganic Chemistry

ISRN Analytical Chemistry

ISRN Organic Chemistry

ISRN Physical Chemistry

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