Here we demonstrate the synthesis of multifunctionalised benzimidazoles through the coupling of o-phenylenediamine with aldehydes by using Copper (II) hydroxide as an efficient solid catalyst in methanol at room temperature. The Copper (II) hydroxide solid catalyst gave better yields (80% - 99%) in short reaction time (4 - 8 h). These commercially available cheap catalysts are more active than many reported expensive heterogeneous catalysts. Using the Copper hydroxide fresh catalyst, the yield of product 3a was 98%, while the recovered catalyst in the three subsequent cycles gave the yield of 94%, 90% and 88% respectively.
Encouraged by these results, we examined several substituted aldehydes including aromatic, heteroaromatic and aliphatic groups, which underwent smooth conversion to afford a wide range of benzimidazoles (). Aromatic aldehydes containing both electron-donating and electron-withdrawing groups worked well in this reaction. Unfortunately metal hydroxides are not explored much in the synthesis of various benzimidazoles. It was found that transition metal oxide is more effective for oxidation than the corresponding zero-valent metal powders. Open air and copper hydroxide both may be sources for the oxidation process. Here, it seems that copper hydroxide solid catalyst is acting as bifunctional like Lewis acid as well as oxidative reagent.
Hexanedioic acid, polymer with N-(2-aminoethyl)-N′-[2-[(2-aminoethyl)amino]ethyl]-1,2-ethanediamine, N-(2-aminoethyl)-1,2-ethanediamine and (chloromethyl)oxirane, sulfate
Polymer of 4,4′-(1-methylethylidene)bisphenol polymer with (chloromethyl)oxirane, 4,4′-(1-methylidene)bisphenol, alkylphenols, alkanolamines and alkylamines, lactic acid salt of
Phenol, 4,4′-(1-methylethylidene)bis-, polymer with 4-amino-α,α,4-trimethylcyclohexanemethanamine, 5-amino-1,3,3-trimethylcyclohexanmethanamine, (chloromethyl)oxirane, 2,2,4-trimethyl-1,6-hexanediamine and 2,4,4-trimethyl-1,6-hexanediamine
68. Shin D, Lee SC, Heo YS, Lee WY, Cho YS, Kim YE. . Design and synthesis of 7-hydroxy-1H-benzoimidazole derivatives as novel inhibitors of glycogen synthase kinase-3beta. 2007;17:5686-9
In summary, benzimidazole and its derivatives were synthesized by the coupling of o-phenylenediamine with various aldehydes using commercially available Cu(OH)2 as an efficient recyclable solid catalyst under open oxygen atmosphere at room temperature using methanol as solvent. Various multifunctionalised Benzimidazoles could successfully be synthesized by using the Cu(OH)2 catalyst with acid sensitive, sterically hindered and substituted aromatic and aliphatic aldehydes. The reactions were performed in methanol and the catalyst could be reused for several cycles without much decrease in activity. The salient features of the present method include mild conditions, short reaction times, high yields, recyclable catalyst, large scale synthesis and simple procedure. These catalysts could replace the existing homogeneous and expensive heterogeneous catalysts which are currently being used in the synthesis of various industrially important and biologically active benzimidazoles.
In addition we have also carried out scale up experiments with 1.08 g of o-phenylenediamine and 1.27 g of benzaldehyde using 10 mol% of Copper hydroxide catalyst at room temperature in methanol. The Cu(OH)2 catalyst gave 98% of product 3a, that is almost similar to the yield obtained in Entry a, indicating that the catalyst could be easily used on a large scale. In the present work, the catalytic activity of the Cu(OH)2 has been studied for synthesis of multifunctionalised benzimidazole derivatives at room temperature. It has been found that these commercially available catalysts are very cheap, recyclable and showed superior activity at room temperature than Co(III) salen , and cheaper than many other expensive heterogeneous catalysts [32,33]. All the synthesized compounds (3a-3v) colour, melting points were checked and characterized by using IR and 1H-NMR spectra data was given below.
Many heterogeneous catalysts [32,33] and expensive Co(III) salen complexes  were used in the synthesis of various benzimidazoles. But all they have not achieved the products using aliphatic aldehydes. The present catalyst is simple, recyclable, green catalyst and more convenient than many catalysts presented in the above introduction. These catalysts were also found to be very active in the synthesis of benzimidazoles using an acid sensitive furfuraldehyde (3f) and bulky naphthaldehyde (3g), also worked well. Various substituted aldehydes have been used with similar success to provide the corresponding benzimidazoles in high yields (80% - 99%).
4,4′-(1-Methylethylidene)bisphenol, polymer with (chloromethyl)oxirane, and 2(dimethylamino)ethanol-blocked polyalkylenepolyphenylene isocyanate, lactates (salts)