S. S. Gurav, K. T. Waghmode, O. Lotlikar
Aug 12, 2022
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Journal
Organic Preparations and Procedures International
Abstract
Imidazoles have piqued the interest of researchers in modern organic synthesis, and this can be attributed to their unique physicochemical properties and medicinal value. Several imidazoles have widespread medicinal applications, including antibacterial, antiviral, anti-inflammatory, antinociceptive, and anticancer properties. Other compounds in this class function as inhibitors of kinases, modulators of p-glycoproteins, and glucagon receptor antagonists. Due to the broad array of applications of substituted imidazoles, considerable efforts have been made for their synthesis from benzil, aromatic aldehydes, and ammonium acetate, taking advantage of such diverse catalysts as picolinic acid, L-cysteine, BiCl3, iodine, ionic liquids, polymer-supported nanocatalysts of iron oxides, Y(TFA)3, pumice, light-emitting diodes, and sulfonic and phosphoric acid catalysts. Recognizing the significance of imidazoles, it is a desirable goal to develop new methods that avoid hazardous reaction conditions, expensive reagents, and complex workup and purification procedures. With these considerations in mind, we now report a new, simple and mild one-pot protocol for the synthesis of 2,4,5-trisubstituted imidazoles. This method employs Amberlite IR-120(H) as an active and stable catalyst (Scheme 1). Amberlite IR-120(H) is an acidic styrene-divinylbenzene cross-link polymer-supported material bearing sulfonic acid groups. The catalyst has particle size 620-830 mm and thus provides large active sites. The catalyst withstands high temperatures. As a model, we first chose the reaction of benzil (1mmol), p-chlorobenzaldehyde (1mmol), and ammonium acetate (1mmol) to produce the related 1H-imidazole. The reaction was studied in the absence of catalyst, but the yield was low; then the reaction was carried out by employing 0.15 g of catalyst in ethanol at room temperature and showed a substantial increase in yield (Table 1). The reaction was further examined by varying the temperature and concentrations of catalyst and NH4OAc. The best results (Table 1, entry 13) were obtained with molar ratios of benzil:p-chlorobenzaldehyde:ammonium acetate of 1:1:3.5, in the presence of 0.15 g of catalyst, in ethanol at reflux for 1.5 h.