The use of process simulators has increased dramatically due to their ability to solve complex engineering problems. However, most simulators use a black-box modeling approach, which hinders the application of derivative-based optimization models. This work aims to present a case study of the glycerol ketalization reaction by integrating the Aspen Plus® simulator with MEIGO, an optimization tool available for MATLAB®. The kinetic parameters of the reaction were estimated using a Python algorithm. The simulation was validated, and the optimization of the reactive section was performed using an Enhanced Scatter Search method. After optimization for 80% glycerol conversion, the temperature, acetone:glycerol molar ratio in the reactor feed, and reactor volume were 80 °C, 8.83, and 24.17 m³, respectively, for processing 5.149 m³/h of glycerol. The integration of Aspen Plus® with MATLAB® using the MEIGO add-on is shown as a valid strategy for optimizing complex problems involving black-box models.
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