Flow synthesis of n-substituted 5-benzylidinethiazolidine-2,4-dione

Abstract

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).