An Efficient Procedure for the Synthesis of Benzimidazoles Using H<sub>2</sub>O<sub>2</sub>/SiO<sub>2</sub>-FeCl<sub>3</sub> System
An Efficient Procedure for the Synthesis of Benzimidazoles Using H2O2/SiO2-FeCl3 System
Journal of the Korean Chemical Society. 2010. Oct, 54(5): 579-581
Copyright © 2010, The Korean Chemical Society
  • Received : January 06, 2010
  • Accepted : May 04, 2010
  • Published : October 20, 2010
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Abbas Fazlinia
Mohammad Hossein Mosslemin
Hesamaddin Sadoughi

Solid silica supported ferric chloride (SiO 2 -FeCl 3 ) catalyzed one-step synthesis of various benzimidazoles from o -phenylenediamine and aldehydes using H 2 O 2 as the oxidant. The salient features of this method are simple and convenient procedure, easy purification and shorter reaction times.
Nitrogen compounds are basic building blocks in animal biology and life. 1 Nitrogen heterocycles are of special interest because they constitute an important class of natural and nonnatural products, many of which exhibit useful biological activities. 1 A series of heterocycles containing nitrogen atom is benzimidazole. Substituted benzimidazoles have found applications in diverse therapeutic areas including antiulcers, antihypertensives, antivirals, antifungals, anticancers, and antihistaminics to name only a few. 2 The widespread interest in benzimidazole containing structures has prompted extensive studies for their synthesis. Thus a number of routes have been developed for synthesis of 2-substituted benzimidazoles. 3 But some of these procedures have certain limitations such as tedious process, long reaction times, harsh reaction conditions, and low yields.
In our program, we targeted a simple and convenient method for the synthesis of 2-substituted benzimidazoles via one-pot cyclocondensation-oxidation of o-phenylenediamine and aldehydes using silica supported ferric chloride (SiO 2 -FeCl 3 ) as catalyst under thermal conditions ( 1 ).
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Preparation of 2-aryl benzimidazole derivatives
All reagents were purchased from Merck and Aldrich and used without further purification. All yields refer to isolated products after purification. Products were characterized by spectroscopic data (IR, NMR spectra) and melting points with authentic samples. The NMR spectra were recorded on a Bruker Avance DEX 300 MHz instrument. The spectra were measured in DMSO-d 6 relative to TMS (0.00 ppm). IR spectra were recorded on a JASCO FT-IR 460plus spectrophotometer. All of the compounds were solid and solid state IR spectra were recorded using the KBr disk technique. Melting points were determined in open capillaries with a BUCHI 510 melting point apparatus. TLC was performed on silica gel polygram SIL G/UV 254 plates.
- Preparation of SiO2-FeCl3.
In a 250 mL flask, ferric chloride hexahydrate (FeCl 3 .6H 2 O) (1 g) was dissolved in acetone (50 mL) and silica gel (10 g) (SiO 2 for column chromatography; 70 - 230 mesh) was added to this mixture and was vigorously stirred under vacuum until acetone was evaporated. A pale yellowish powder was obtained. This powder was kept in oven at 100 ℃ for 1 h to give the active catalyst. 4
To a mixture of o -phenylenediamine (1 mmol) and aryl aldehydes (1 mmol) aq. 30% H 2 O 2 (7 mmol) and SiO 2 -FeCl 3 (0.1 g) were added and the mixture was heated at 150 °C in a sand bath for the 30 min. The progress of the reaction was monitored by TLC (eluent: n -hexane-EtOAc, 7:3). When the starting materials had completely disappeared the mixture was cooled at room temperature, and then the solid was dissolved in CH 2 Cl 2 (10 mL). The catalyst was separated and the organic layer was washed with water (2 × 10 mL) and dried under MgSO 4 . The filtrate was evaporated and the corresponding benzimidazole was obtained as the only product after recrystallization in aq. Ethanol (25%) ( 1 ).
As summarized in 1 , several different aromatic aldehydes and o-phenylenediamine were reacted in the presences of SiO 2 -FeCl 3 as catalyst under thermal solvent-free conditions resulting the corresponding 2-substituted benzimidazoles in good to high yields ( 1 and 1 ). The reactions were performed with benzaldehyde containing electron withdrawing groups as well as electron-donating groups and gave the desired products at short reaction times with excellent yields ( 1 ).
Synthesis of benzimidazole derivatives using SiO2-FeCl3as catalyst
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aYields refer to pure isolated products. All known products have been reported previously in the literature and were characterized by comparison of IR and NMR spectra with authentic samples.3
The work-up procedure is very clear-cut; that is, the products were isolated and purified by simple filtration and extraction from CH 2 Cl 2 . Our protocol avoids the use of dry media during the reaction process, making it superior to the previous methods.
In a typical experiment, after completion of the reaction CH 2 Cl 2 was added into the reaction mixture until solid crude product was dissolved. Then, the SiO 2 -FeCl 3 as catalyst was isolated from the reaction mixture by simple filtration. In continuation of work-up, the organic layer was washed with water and dried under MgSO 4 . The filtrate was evaporated and the corresponding benzimidazole was obtained after recrystallization in ethanol ( 1 ).
The suggested mechanism of the SiO 2 -FeCl 3 catalyzed transformation is shown in 2 .
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On investigating the reaction mechanism and in accordance to the reported procedures, the formation of benzimidazoles cause to be connected with the formation of intermediate Schiff base A which is equilibrated with the hydrobenzimidazole B that is produced by intra-molecular participation of the o -hydroxyl group ( 2 ).
The mechanisms of the catalytic decomposition of H 2 O 2 by Fe(III) in homogeneous aqueous solution have been the subject of numerous studies. The mechanisms involved may be quite complex and are not clearly established. According to previously reports, different reactive species are supposed to be formed: free- and bound-hydroxyl radicals, hyper-valent iron species (Fe(IV), Fe(V)) ( Scheme 3 ).
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The route can be shown as SiO 2 -FeCl 3 (OOH); SiO 2 -FeCl 3 O and SiO 2 -FeCl 3 (OH). 5 Finally, the following oxidative dehydrogenation of adduct B in the presence of the SiO 2 -FeCl 3 O complex affords the desired 2-arylbenzimidazoles ( 2 ).
In conclusion, we have demonstrated that SiO 2 -FeCl 3 is an efficient and heterogeneous catalyst for the synthesis of a variety of benzimidazole derivatives using aryl aldehydes and o -phenylenediamine under solvent-free conditions. The reactions were carried out under thermal conditions with short reaction time to produce the corresponding product in good to high yields.
We are thankful to the Islamic Azad University of Yazd Research Council for the partial support of this research.
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