Concentrated Solar Radiation (CSR) assisted two-step, one-pot synthesis of (S)-3-(4-phenylpiperazin-1-yl) propane-1,2-diol (Levodropropizine)

Background: The recent energy shortage has drawn much attention to synthesizing active pharmaceutical ingredients (API) using green chemistry concepts like renewable energy sources and solvents. The concentrated solar radiation (CSR) technique has several advantages, including simple, affordable, energy and time-efficient for synthesizing active pharmaceutical ingredients and new chemical entities. Here, we successfully developed a two-step, one-pot synthesis of levodropropizine for the first time using CSR as a clean energy source and in a green solvent. Objective: To synthesize levodropropizine using concentrated solar radiations to save energy and improve yields while maintaining essential properties like chirality and physical properties. Methods: Levodropropizine was synthesized in two steps and in one pot method in a glass apparatus under concentrated solar radiation using a Fresnel lens measuring 20 cm (l) X 20 cm (b). The outcome was compared with the one obtained from the conventional heating method. X-ray crystallography, FTIR, NMR, polarimetry, HPLC-MS, chiral HPLC, DSC, and DTA characterized the Levodropropizine produced by CSR and conventional heating. The product synthesized by CSR was in agreement with the one synthesized by conventional heating. Results: As shown in scheme-1 a two step, one pot synthetic protocol for Levodropropizine using concentrated solar radiations resulted in 87% yield in 38 minutes while conventional heating method took about 6 hours with 77% yield. Conclusion: A two-step, one-pot, environmentally friendly, and straightforward approach to synthesizing Levodropropizine using concentrated solar radiation has been established; this method minimized the reaction time from 6.08 h. to 38 minutes, saving up to 90.89% of the energy. Different analytical techniques for physical characterization, such as x-ray crystallography, DSC, DTA, and chemical identity and purity by FTIR, NMR, Polarimetry, chiral HPLC, and LC-MS, thoroughly characterized Levodropropizine synthesized by CSR.