One of the bottlenecks in the pharmaceutical industry is drug production scaleup, 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.

Microreactor technology can help to reduce the time to market new drugs. It was applied to produce (Z)‐5‐benzylidenethiazolidine‐2,4‐dione, a heterocyclic intermediate in the synthesis of various drugs. Ethanol was the optimum solvent and piperidine the best catalyst in the batch process. The continuous/microreactor process exhibited a much better performance than the batch process. The productivity, which was strongly influenced by solvent and temperature, reached a maximum at 160 °C using methanol as solvent. A kinetic/thermodynamic study indicated that the reaction followed the second‐order model and allowed estimating its main thermodynamic parameters. A product recovery protocol was finally proposed. The microreactor proved an efficient alternative to the batch reactor in scaling up the production of active pharmaceutical ingredients.

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Process intensification based on micro reactor technology allows safe manner and a new pathway to run organic synthesis due to its intrinsic characteristics, and can reduce time-to-market of new drugs. The main objective of this work was to study the batch and flow reaction of five n-substituted 5-benzylidenethiazolidine-2,4-dione heterocyclic intermediates present in the synthesis of glitazone class drugs, in capillary micro reactor. Batch process was conducted with ethanol as solvent at the boiling point and pyrrolidine as promoting base of the reaction. Higher yields were obtained in shorter reaction times in temperatures above solvent boiling point. Also, we evaluated that 3.8 micro reactors in parallel would be necessary to reach the same mean molar flow rate of a 60 mL batch reactor. Kinetic and thermodynamic study indicated that the reaction followed the second-order model and allowed estimating its main thermodynamic parameters. The continuous flow micro reactor proved to be an efficient alternative to the batch process in scaling up the production of Active Pharmaceutical Ingredient intermediates (APIs).

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