Thoriq, Mohammad Firdaus Akmal, Rizki Fitriani, Muhammad Yogi Saputra, Atthar Luqman Ivansyah, Deana Wahyuningrum
Risperidone is an important atypical antipsychotic that still requires a more efficient, scalable, and environmentally friendly synthetic route. In this study, we synthesized a series of imidazolium-based ionic liquids, namely [EMIm]Br, [BMIm]Br, [BMIm]Cl, [DMIm]Br, [DDMIm]Br, and [BnMIm]Cl. These compounds were employed as green media and catalysts for the microwave-assisted organic synthesis (MAOS) of risperidone. The optimum conditions using [EMIm]Br with 3.2 M Na₂CO₃, 100 W irradiation power, 70 °C, and 2 h reaction time afforded risperidone in the highest yield of 95%. This yield was superior compared with conventional heating under similar conditions. Product characterization was confirmed by FTIR, 1H NMR, 13C NMR, and HRMS. The successful synthesis of risperidone was further evidenced by the appearance of proton signals in the 1H NMR spectrum at δ 2.54 ppm and 2.77 ppm, corresponding to two hydrogen atoms with triplet multiplicity. These proton signals correlate with the newly formed bridging carbon between the piperidine ring and the pyridopyrimidine moiety of the two risperidone precursors. Computational analyses, including DFT and molecular docking, provided additional support, showing HOMO–LUMO stability and favorable binding affinity of risperidone with relevant biological targets. These findings demonstrate that imidazolium-based ionic liquids are effective media and catalysts for the microwave-assisted synthesis of risperidone with high yield, consistent with the principles of green chemistry. © 2025 Elsevier B.V.
Department of Chemistry, Organic Chemistry Division, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Bandung, 40132, Indonesia; Department of Chemistry, Inorganic and Physical Chemistry Division, Institut Teknologi Bandung, Jalan Ganesha No. 10, West Java, Bandung, 40132, Indonesia; Department of Chemistry, Faculty of Sciences, Institut Teknologi Sumatera (ITERA), Jalan Terusan Ryacudu, Way Hui, Lampung Selatan, Kecamatan Jati Agung, 35365, Indonesia; Department of Chemistry, Faculty of Science, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore