FLOW SYNTHESIS OF METOPROLOL® IN CAPILLARY MICROREACTORS

• Grant number: 24/23407-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: December 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Mauri Sergio Alves Palma
• Grantee: Danilo Maia da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Microreactor technology is an excellent tool for increasing the efficiency of chemical reactions, as it improves the control of thermal exchange, reaction kinetics, and mass transfer, allowing for increased pharmaceutical production with less waste generation, such as Metoprolol®, a beta-blocker that reduces blood pressure by inhibiting adrenaline receptors. Thus, microreactors enable higher production of these products and precise control of potentially dangerous reactions. This work aims to transpose a synthesis route for Metoprolol® from the conventional batch process to a flow process, using capillary microreactors. The optimal operational conditions in the batch process will be determined by analyzing the influence of temperature, solvent, and reactant concentration, aiming to maximize conversion, yield, and selectivity with a shorter reaction time. After determining the best conditions for the batch process, this reaction will be transposed to the flow process, which offers significant advantages over the batch process, such as higher reaction speed, conversion, yield, and product selectivity, in addition to safety when handling toxic reagents and products. Once these conditions are found in the microreactor, the reaction kinetics will also be determined, along with the rate constant, k, and thermodynamic properties such as Activation Energy (Ea), using the Arrhenius model to fit experimental data, and delta H*, delta S*, and delta G*, using the Eyring model and the van't Hoff thermodynamic relationship.