Benzimidazole solvent-free reactions

A simple, rapid, and efficient method for the preparation of benzoxazoles, benzimidazoles, and oxazolo[4,5- ]pyridines by the reaction of ortho esters with o-aminophenols, o-phenylenediamine, and 2-amino-3-hydroxypyridine in the presence of SSA under heterogeneous and solvent-free conditions is reported (Scheme 6.8). The significant features of this method are short reaction times, high yields of the products, mild reaction conditions, solvent-free reactions, cheapness, nontoxicity, and reusability of the catalyst (Baltorka et al., 2008). 

Catalyhc Zn0 H202 (0.1 mmol lmL/2 mmol of the substrate) has been explored [91] for the synthesis of benzimidazole and quinoxaline derivahves at room temperature (Scheme 62). o-Phenylenediamines have been shown to react with variety of aliphatic as well as aromatic aldehydes resulting in substituted benzimidazoles in high yields. The reactions are completed within 20 min in case of aromatic aldehydes whereas the aliphatic ones need 1 h for complete conversion. Replacing aldehydes with 1,2-diketones results in the synthesis of quinoxaline derivatives within 10 min (Scheme 62). Zinc acetate has also been used as a catalyst for solvent-free synthesis of benzimidazole derivatives at room temperature with approximately 90% yields. The solvent-free reaction is carried out using substituted o-phenylenediamines and aldehydes (both aryl and alkyl) [92] (Scheme 62). 

One key area of current research in the synthesis of benzimidazoles is the continued search for mild reaction conditions to avoid the harsh dehydrating conditions often required in the Phillips-type condensation/ cyclization approach. A recent report by Liu and co-workers exemplifies a mild variant of the classical orthoester condensation, which may soon find utility in drug synthesis. In this report, a variety of substituted 1,2-diaminobenzenes is condensed with triethyl-orthoesters using catalytic Ga(OTf)3. Under these solvent-free conditions, the reactions proceed at room temperature, with very short reaction times (5-90 min), thus providing a convenient new method for benzimidazole synthesis. 

Paul and Basu (2012) developed an efficient and highly selective synthesis of functionalized 1,2-benzimidazoles under solvent-free conditions at ambient temperature using eco-friendly ferric sulfate soaked with silica (Fc2(S04)3-Si02). The reaction is illustrated in Scheme 6.11. This new method requires only inexpensive, eco-friendly reagents and the recyclable catalyst. 

Benzimidazoles are prepared readily by condensation reaction of ortho-esters with o-phenylenediamines in the presence of KSF clay under solvent free conditions using focused microwave irradiation (Scheme 62). ... 

Saha, D., Saha, A., and Ranu, B. C. (2009). Remarkable influence of substituent in ionic, liquid in control of reaction simple, efficient and hazardous organic solvent free procedure for the synthesis of 2-aryl benzimidazoles promoted by ionic Uquid, [pmim]BF4. Green Chem., 11, 733 737. 

Basu and Mandal have presented a comprehensive review on various sustainable synthetic strategies leading to benzimidazoles, quinoxalines, and their congeners highlighting the scope, limitations, and plausible mechanisms. These heterocyclic scaffolds have already drawn considerable interests to the researchers at large for their well-established biological and pharmaceutical properties. The authors have given emphasis on the sustainable processes that involve solid-phase synthesis, biomimetic synthesis, combinatorial synthesis, various catalytic methods, and reactions promoted by different solid sinfaces, solvent-free or on-water conditions or xmder microwave irradiation. This overview would serve as a useful somce of information to the readers in this particular area of interest. 

Binuclear complexes with bridging trimethyltriazoldiylidene ligands were also used in TH and p-alkylation reactions. Thus, complexes 124 and 125 were applied for TH of ketones and imines in KOH/i-PrOH (Figure 13.14). The reductions of ketones and N-ben lidene anilines were complete within 1 h. Related 126 and 127 ruthenium complexes were investigated as catalysts in the p-alkylation of secondary alcohols with primary alcohols. Such catalytic systems were very selective and more active than the previously reported catalysts. Cationic Ru" complexes 128 with a picolyl-functionalized NHC catalyzed the N-alkylation of amines under mild conditions. Ru" complexes 129, with benzimidazol-2-ylidene, gave excellent yields of <99% for the alkylation of various amines using benzylic and aliphatic alcohols at 130 C under solvent free conditions. ... 

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