Systematic solvent screening for aldol condensation reaction using design of experiments

This thesis aims to optimize the acyloin condensation reaction between formaldehyde and nonanal as part of the IMPD4Cat project, which focuses on developing sustainable catalytic processes. Particular attention was given to the influence of the solvent and key operating parameters, namely temperature (T), reaction time (t) and the reactants molar ratio (R). To achieve this, the Design of Experiments (DoE) methodology, specifically a Central Composite Design, was used to plan the experiments. Process performance in terms of conversion and selectivity was quantified using gas chromatography (GC), while statistical analysis and modelling were conducted with Minitab software through response surface regression and response optimization. The results provided a detailed picture of the influence of the three aprotic solvents tested: toluene, tetrahydrofuran (THF), and dichloromethane (DCM). Toluene proved to be the optimal solvent, yielding high conversion (X=95.69%) and selectivity (S=67.20%) under the optimal conditions of T=25 °C, t=18 h and R=2.45, along with robust predictive models. While THF showed promising results, its statistical model was not predictive due to the high intrinsic variability of the system. DCM, on the other hand, yielded very low performance and was discarded from future studies. For future developments, it is suggested to delve deeper into the analysis of toluene using more complex models. As for THF, since its results are promising but the solvent is toxic, it is recommended to test alternative, greener solvents with similar characteristics. Additionally, the observation of secondary peaks during GC analysis provides a clear direction for future research aimed at identifying the chemical nature of these byproducts and developing targeted strategies to limit their formation.