Public Thesis defense - IMCN

Influence of the solvent on the crystallization of multi-component compounds comprising chiral molecules by Joséphine de MEESTER

Pour l'obtention du grade académique de Doctorat en Sciences

Crystallization-based resolution methods are crucial in industrial applications, yet the influence of solvent in these processes remains underexplored. Therefore, this work investigates the pivotal role of the solvent in crystallization phenomena, focusing specifically on chiral molecules and on the development of resolution methodologies.

This study investigates three distinct systems.

First, we explored the interplay between two racemic compounds, BINOL and trans-cyclohexane-1,2-diamine, in various solvent environments. The high number of obtained phases emphasizes the potential complexity introduced by the solvent and its impact on the efficiency of chiral resolution processes.

Second, diastereomeric resolution of BINOL using (R,R)-N,N′-dimethyl-1,2-diphenylethane-1,2-diamine was developed in two achiral solvents, toluene and benzene. We demonstrated that the solvent choice dictates which thermodynamic form will be obtained, driving to the selective recovery of either (S)- or (R)-BINOL depending on which solvent is used.

Finally, we developed the preferential crystallization of the Mandelic acid-Nefiracetam cocrystal-conglomerate system, using pressurized CO₂ as an antisolvent. First, we established the proof-of-concept of the process. Secondly, system optimization enabled simultaneous resolution of both enantiomers.

These investigations emphasize the underestimated role of solvent, revealing its potential as an active tool in crystallization processes. Indeed, solvent choice can shape resolution processes, tailoring crystalline forms to target a specific enantiomer.

Jury members :

• Prof. Tom Leyssens (UCLouvain) (Supervisor)
• Prof. Evelyne Van Ruymbeke (UCLouvain) (Chairperson)
• Prof. Sophie Hermans (UCLouvain) (Secretary)
• Prof. Johan Wouters (UNamur)
• Prof. Pascale Subra-Paternault (Univ. Bordeaux, Fr.)
• Dr. Christelle Harscoat-Schiavo (Univ. Bordeaux, Fr.)

Pay attention : the public defense of Joséphine de MEESTER will also take place in the form of a videoconference

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