One-pot synthesis of substituted imidazole derivatives by a new designed BiFeO3/CuWO4 heterojunction nanocatalyst

In this work a novel heterojunction nanocatalyst have been synthesized and employed as a highly efficient and recoverable heterogeneous catalyst for the one pot three-component synthesis of substituted imidazoles under mild reaction conditions in short reaction times and good to excellent yields. Analytical methods including Fourier transform infrared (FT-IR) and X-ray diffraction (XRD) were used for the catalyst characterization.


Introduction
Development of new multicomponent reactions (MCRS) are an area of considerable interest due to the fact that the products are formed in a single step and also the variety could be achieved only by changing the reaction components [1].Imidazole derivatives are a very interesting class of heterocyclic compounds because they have many pharmacological properties and play important roles in biological process.The imidazole compounds are known to possess NO synthase inhibition and antifungal, antimycotic, antitumor, antibiotic, antibacterial, antiulcerative, and CB1 receptor antagonistic activities [2,3].Various substituted imidazoles act as B-Raf kinase [4], glucagon receptors [5], inhibitirs of p38 MAP kinase [6], plant grown regulators [7], therapeutic agents [8], and pesticides [9,10].These propellants have engendered considerable interest among synthetic organic and medicinal chemists in recent years.Accordingly, a number of synthetic methods have been reported for the synthesis of 2,4,5-trisubstituted imidazoles.These methods involve condensation of benzil or benzoin, aryl aldehydes and ammonium acetate by using various catalytic systems [11,12].But, some of these synthetic methods are associated with one or more drawbacks such as using expensive reagents, long reaction times, purifications, complex work-up, generation of large amount of toxic wastes, strongly acidic conditions, high temperature, poor yields and occurrence of side reactions.Owing to the wide range of pharmacological and biological activities, the development of effective, high yielding, economical, clean and mild environmental benign protocols is still desirable and is in demand.Moreover, the design of valuable, effective and recoverable catalysts is important for the both environmental and economical point of view.Herein we wish to report a new efficient and practical route for the synthesis of trisubstituted imidazoles by the condensation reaction of benzil or benzoin, aryle aldehydes and ammonium acetate catalyzed by novel BiFeO 3 /CuWO 4 heterojunction particles.To the best of our knowledge, this is the first report of design, preparation, and characterization of BiFeO 3 /CuWO 4 heterojunction and its application as a heterogeneous catalyst in organic reactions.This novel approach has several superiorities as a compared with the previous reports for the synthesis of substituted imidazole derivatives and opens an important area to the use of environmentally benign and recoverable heterogeneous nanocatalyst in the synthesis of pharmaceutically important heterocyclic compounds (Scheme 1).

Synthesis of BiFeO3
Bismuth ferrite, BiFeO 3 was synthesized according to a modified sol-gel method [16].A transparent multi-component solution was prepared by mixing bismuth and iron salts.Bismuth nitrate pentahydrate, Bi(NO 3 ) 3 •5H 2 O was dissolved at room temperature in a mixture of 2-methoxyethanol and acetic acid.Then it was mixed with equimolar amount of iron nitrate nonahydrate, Fe(NO 3 ) 3 •9H 2 O by constant stirring at room temperature.The precursor solution was dried at 80 °C for about 12h to obtain the BiFeO 3 xerogel powder.Then the xerogel powder was ground, and the powder was annealed at 600 °C for 30 min in air or N 2 atmosphere in the furnace.
During the annealing procedure, heating and cooling rates of furnace were maintained at a rate of 4 °C/min.
FT-IR spectrum of BiFeO 3 , CuWO 4 and BiFeO 3 /CuWO 4 structures have also investigated and shown in Fig. 2. In the FT-IR spectrum of BiFeO 3 shown in Fig. 2. the broad band around 3442.5 cm -1 arises from the antisymmetric and symmetric structure of H 2 O and OH -groups.Specifically, two strong absorptive peaks around 545.8 and 441.7 cm -1 are attributed to the Fe-O stretching and O-Fe-O bending vibrations, being characteristics of the octahedral FeO 6 groups in the perovskite compounds.The formation of perovskite structure can be confirmed by the presence of metal-oxygen band [17].In the CuWO 4 FT-IR spectrum the bands appear at a lower frequency is assigned to the deformation mode of the WO 4 tetrahedra.The absorption bands that appear in the 901 cm -1 assigned to stretching mode of W-O bonds in junction with WO 4 tetrahedra.Furthermore, the bands appearing in the 760 cm -1 is due to the Cu-O stretching band.The appearing absorption bands below 600 cm -1 might be responsible for the deformation modes of W-O bonds in the WO 4 tetrahedra or the deformation modes of W-O-W bridges.Presence of several splitting absorption peaks at 569, 585, 774, and 902 cm -1 can attributed to the CuWO 4 phase.Furthermore, annealing of the sample at higher temperatures (600℃) creates stronger W-O bonds due to the improvement of the sample crystallinity.As illustrated in the FT-IR spectrum of the BiFeO 3 /CuWO 4 (Fig. 2.) separate and common absorption peaks of BiFeO 3 and CuWO 4 can be seen with the composite formation.A probable mechanistic pathway for the formation of 2,4,5-trisubstituted imidazoles is outlined in scheme 2. According to the mechanism, it can be proposed that the enormous active centers or unsaturated metals in the BiFeO 3 /CuWO 4 heterostructure composite are responsible for the initial activation of the carbonyl group of aldehydes to facilitate nucleophilic addition of ammonia.In more details, it can be proposed that the hydrogen atoms in ammonia and free-orbitals of the metal centers in BiFeO 3 /CuWO 4 having the lewis acidic properties, are responsible for the activation of carbonyl groups, and thus increase the rate of imine production through coordination bonding for nucleophilic attack of amines (Scheme 2

Conclusions
In summary, we have introduced a novel BiFeO 3 /CuWO 4 heterojunction structure as a highly effective and recoverable heterogeneous catalyst for the one-pot synthesis of trisubstituted imidazoles under mild solvent free conditions.The high catalytic activity of BiFeO 3 /CuWO 4 is further highlighted when compare with the other catalysts in this reaction.The several advantages of BiFeO 3 /CuWO 4 as catalyst are easy to prepare,recycled several times and easiness of separation.In addition to the mild reaction conditions, easy work up, operational simplicity, giving the desired products in good to high yields are the key advantages of this protocol.We have believe that this procedure is appropriate, user-friendly process and economic for the synthesis of substituted imidazoles of biological and medicinal procedure.
).It is noteworthy that ammonia itself is produced in situ by decomposition of ammonium acetate in the presence of catalyst.It is considerable that the byproducts of this tandem MCR reaction are mainly water molecules which can be sorbed to the BiFeO 3 /CuWO 4 .Highly catalytic activity of magnetic BiFeO 3 /CuWO 4 can be attributed to the catalytic temper of metal centers in both of BiFeO 3 and CuWO 4 structure that can easily coordinate with the substrates.
Scheme 2. Plausible mechanism of the reaction.