Glycerol Containing Triacetylborate Mediated Syntheses of Novel 2-Heterostyryl Benzimidazole Derivatives: A Green Approach

A very simple, mild, efficient, and novel green methodology has been developed for the syntheses of some 2-hetero/styryl-benzimidazoles. Title compounds were synthesized by the condensation of -phenylenediamine with cinnamic acids at 150–180°C for 5-6？h using glycerol containing triacetylborate (10–20？mol%) as the reaction medium. In an alternative approach, condensation of 2-methylbenzimidazole derivatives with aromatic aldehydes was done using glycerol containing triacetylborate (10–20？mol%) as the reaction medium. 1. Introduction Using solvents in chemical synthesis represents a greater challenge in terms of green chemistry and among them solvents like water, PEG-600, and ionic liquids have proved to be potential green solvents for organic synthesis. In the past [1], glycerol as solvent has not been used extensively for organic synthesis and in recent years, various developments have been made to prove that glycerol can be used as an alternate solvent and can feasibly be considered as an efficient green solvent [2, 3]. Cinnamic acids and its derivatives (i-iv) (Figure 1) such as ethyl cinnamate, sodium cinnamate, and benzylcinnamate have century old history as potential antituberculosis agents [4–7]. Benzimidazole scaffold being an important pharmacophore and privileged structure in medicinal chemistry [8, 9], a new series of 5-(bromo/nitro)-2-styryl-benzimidazoles were synthesized earlier using cinnamic acids in ethylene glycol under reflux conditions and showed good antimicrobial and antitubercular activities (vii) [10, 11]. 2-Styryl-benzimidazoles and its analogues (v) were also reported as MAO-B inhibitors [12], in which the styryl compounds were synthesized using 2-methylbenzimidazole condensed with aromatic aldehydes refluxing at 180°C for 24？h (Figure 1). Figure 1: Cinnamic acid and its derivatives showing various biological activities. Recently, some new styryl benzimidazoles were reported as probes for imaging neurofibrillary tangles in Alzheimer’s disease [13], in which new iodo derivatives of styryl-benzimidazoles were prepared by the condensation of substituted -phenylenediamines with cinnamaldehydes refluxing in DMF [13]. Other methods for the preparation of 2-styrylbenzimidazoles involves the use of PPA at 200°C gave a low 30% yield [10] and the conventional Phillips method, in which -phenylenediamine condensed with cinnamic acids refluxing in 4？N HCl, for the synthesis of 2-styrylbenzimidazoles, resulted in the recovery of starting material [10]. The widespread interest in benzimidazole containing skeletons having a wide spectrum of