Microreactor Technology as a Tool for the Synthesis of a Glitazone Drug Intermediate

One of the bottlenecks in the pharmaceutical industry is drug production scale-up, which can be performed by microreactor technology. Such an approach was applied to the synthesis of (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione, a bioactive aromatic heterocyclic compound belonging to the class of glitazones. n-Propanol was the best solvent and piperidine the best catalyst for the batch reaction, which was completed in only 5.5 h. In the microreactor, the productivity was almost independent of solvent. The microreactor behaved as a plug-flow reactor and operated at a steady state for ten hours without efficiency loss. The results suggest that microreactors may replace batch reactors in scaling up drug production.