Synthesis of Fluoroquinolones: Revisiting the Grohe Route in DES-Based Media

Background: The development of greener synthetic routes to active pharmaceutical ingredients (APIs) is a key challenge in sustainable chemistry. Methods: In this work, we explored the use of deep eutectic solvents (DESs) in the multi-step synthesis of a fluoroquinolone following the Grohe method. Results: Several steps of the synthetic sequence were successfully carried out using DESs, achieving moderate to good yields, while operating under mild reaction conditions and reducing purification requirements. Overall, the use of DESs led to an overall yield of up to 43%. A comprehensive greenness assessment, combining EcoScale scoring and the GSK and CHEM21 solvent selection guides, confirmed the superior sustainability profile of DESs, reflecting their lower toxicity, biodegradability, and reduced energy demands. Conclusions: These findings establish DESs as promising, eco-friendly alternatives to volatile and hazardous organic solvents for the synthesis of quinolone derivatives, offering a valuable step toward more sustainable pharmaceutical manufacturing.