SYNTHESIS OF DROPROPIZIN IN FLOW IN CAPILLARY MICROREACTORS

• Grant number: 22/01770-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2022
• End date: March 12, 2023
• Field of knowledge: Engineering - Chemical Engineering - Chemical Technology
• Principal Investigator: Mauri Sergio Alves Palma
• Grantee: Gustavo Manoel Oliveira dos Santos Naziozene
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The present project aims at the synthesis of Dropropizine, an antitussive drug that acts by inhibiting the cough reflex. The synthesis of this intermediate will be carried out using three procedures: reaction of Phenylpiperazine with Glycidol, 3-chloro-1,2-propanediol and Epichlorhydrin, with the main objective of transposing the synthesis reaction from the usual batch processes to the flow process in a capillary microreactor. The Microreate Technology has numerous advantages over the batch process, which lead to an increase in the speed of chemical reactions, high conversion, yield, selectivity and safety when working with reagents and toxic products. Initially, the best conditions in the batch process will be determined, in terms of temperature, concentration of the reaction medium, reaction time necessary to obtain the maximum yield and the most adequate concentration of the base used. The results obtained in batch will determine the best conditions in which the transfer to the flow process in microreactors will be carried out. The kinetics of the reactions and the rate constant, k, will be determined by fitting the conversion results as a function of time, to the appropriate kinetics, and activation energy, Ea, to the Arrhenius model. The thermodynamic parameters in the transition state (”H!, ”G! and ”S!) will be determined based on the Eyring model.