A Hepatic Sinusoids-Based Microtube Reactor for (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione Intermediate Drug Synthesis

Abstract Microreactor technology is considered a breakthrough technology that can replace regular reactors systems as microreactors deliver proper mixing and reaction performance which satisfy both industry and research demands. This drives researchers to develop several microreactor systems with improved characteristics for plenty of applications, including medicine and pharmaceutical applications. In the present study, a microtube reactor system is constructed to produce (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione intermediate drug with a hepatic sinusoids-based micromixer used as the part responsible of mixing the reactants in early stages. (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione is an intermediate drug that belongs to glitazones. A batch reactor system is also constructed for the purpose of comparison. Thiazolidine-2,4-dione (TZD) and p-hydroxybenzaldehyde are used as the main reactants while two compounds are used as catalysts; diethylamine and piperdine. Effects of different parameters such as initial reactants concentration, catalyst concentration, and flow rate and residence time on the product yield and the pressure drop across the micromixer are investigated. Analysis of the collected samples is done using different characterization methods such as High Pressure Liquid Chromatography, Thermogravimetric/Differential Thermal Analysis, X-ray diffraction spectroscopy, Fourier Transform Infrared spectroscopy, and carbon and proton Nuclear magnetic resonance spectra. The microtube reactor system has proven to be more efficient than the batch system. The maximum yield obtained from the microtube reactor system is 97% with a residence time of only 22 min using diethylamine as a catalyst compared with 92% obtained from the batch system using piperdine as a catalyst after 12 hr run. The yield obtained from the microtube reactor system spans from 77% to 97% using diethylamine as a catalyst and from 56% to 84% using piperdine as a catalyst while the pressure drop across the micromixer ranges from 0.9 to 12 kPa.