Piperidinium hydrogen sulfate is used as a very important new catalyst for the synthesis of the biologically active compounds from a series of multi‐substituted imidazole components by the simple reaction of benzyl with different aromatic aldehydes, ammonium acetate, and phenethylamine or butylamine as amine derivatives. The key merits of this method are very shorter reaction times, excellent yield, and ease of stabilization. Furthermore, the produced products can be purified by a non‐chromatographic technique, and the catalyst is reusable. All of these new synthesized components have been characterized and checked from spectral data: IR, 1H‐NMR, and 13C‐NMR spectra and elemental analyses.