Synthesis of intermediates of pioglitazone in batch process and capillary microreactor

• Grant number: 19/07488-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2019
• End date: December 31, 2019
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Principal Investigator: Mauri Sergio Alves Palma
• Grantee: Gabriel Lima Bressan
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chemical-pharmaceutical industries in Brazil employ batch reactors for synthesis processes, however, batch reactors have limitations as to temperature, pressure and mixing efficiency. The use of microreactors emerges as innovation for high demand in industries. The microchannels in the microreactors promote higher and more efficient mass and heat transfer, which enables a process easily manageable in terms of temperature and pressure, enabling higher reaction efficiency and selectivity, safer operations when working with toxic reactants and products, reduction of waste generation and increasing the purity of the product, when compared to batch operating reactors. Pioglitazone, a drug of oral use of the glitazone family, is present on the market with the name of Actos® and is prescribed especially for diabetes mellitus type 2, one of the biggest concerns in the area of health. The present work aims at transposing two intermediate reactions of the seven required for the synthesis of Pioglitazone from the batch process to the continuous flow process in a capillary microreactor. This work also aims to define the best-operating conditions in terms of temperature, solvent, reaction medium total concentration to both processes and the reaction time in the batch process, which corresponds to the mean residence time in the microreactor, in order to maximize the conversion of the limiting reactant, product yield, and selectivity. This project will be developed in the context of the research project financed by Fapesp no. 2017/12830-9 entitled "Synthesis of Pioglitazone, Rosiglitazone, and Lobeglitazone in a continuous flow in capillary microreactors" valid form 10/01/2017 to 09/30/2019.