An Ultrasound Mediated Green Synthesis of Benzimidazolylthiounsaturatednitriles Using Water as a Green Solvent

Reaction of 2-cyanothiomethylbenzimidazole？？1 with an aromatic aldehydes in water under ultrasonic irradiation for 10–13？min gave the corresponding unsaturated nitriles 2a–h which is an efficient and simple method under green conditions. The unsaturated nitrile derivatives were obtained in 86–98% yield with a short reaction time without any tedious workup procedures. 1. Introduction The importance of heterocycles in many fields of science (including organic, inorganic, bioorganic, agricultural, industrial, pharmaceutical, and medicinal chemistry, as well as material science) can hardly be overstated and justifies a long-lasting effort to work out new synthetic protocols for their production [1]. Ultrasound enhances the reactivity of molecules towards many chemical reactions via the process of acoustic cavitation [2]. The assistance of US irradiation efficiently shortens the reaction times. Simple experimental procedure, very good yields, increased selectivity, and clean reaction of many US-induced organic transformations offer additional convenience in the field of synthetic organic chemistry [3–8]. Recently, US has been utilized to accelerate a wide number of synthetically useful organic reactions [9, 10]. In addition to the field of organic chemistry, sonochemistry has also been used in the preparation of micro- and nanomaterials (i.e., protein microspheres) [11]. The α,β-unsaturated nitriles play an important role in drug discovery programs. Various unsaturated nitrile derivatives are also reported to exhibit a wide spectrum of biological properties such as cardiotonic agents. Analogue possessing α,β-unsaturated nitriles at the 17-β position had high activity in natural products. In Digoxin, the unsaturated 17-lactone plays an important role in receptor binding. Saturation of the lactone ring dramatically reduced the biological activity. In Digoxin, if the lactone group at 17th position is replaced with α,β-unsaturated nitriles (–C=C–CN group), there is no loss in biological activity [12, 13] (see Figure 1). Figure 1 Walker et al. reported [14] that condensation of 3-formyl-1H-indole-2-carboxylate with 3-nitrophenyl acetonitrile in piperidine using ethanol under reflux conditions for 70？h gave the corresponding α,β-unsaturated nitriles. Mukarram et al. reported [15] that the condensation of p-substituted benzaldehyde with active methylene compounds gave the corresponding unsaturated nitrile derivative, that is, entacapone, which is used for treatment of Parkinson’s disease. Condensation of benzaldehyde with cyanoethyl acetate in ethanol at RT in the