Sustainable Synthesis of Isosorbide Derivatives in Continuous Flow

Isosorbide is a renewable platform molecule obtained from D-sorbitol and is of growing interest in green chemistry due to its biodegradability and rigid bicyclic structure. The distinct reactivity of its hydroxyl groups enables the selective synthesis of derivatives with applications in pharmaceuticals, polymers, and renewable solvents. This work aims to develop and optimize the continuous synthesis of isosorbide dinitrate, isosorbide mononitrate, and dimethyl isosorbide. Reaction of isosorbide with dimethyl carbonate afforded dimethyl isosorbide, a valuable renewable solvent, in 97% yield after 24 h. Current efforts focus on adapting this process to continuous flow to reduce reaction time and temperature. Regioselective acetylation of the exo hydroxyl group, a key step toward isosorbide mononitrate synthesis, achieved 57% conversion and 92% selectivity. Ongoing studies aim to improve conversion and implement this transformation, followed by nitration, under continuous-flow conditions. Products were analyzed by GC-FID, GC-MS, and NMR spectroscopy techniques.