Publication in Angewandte Chemie International Edition

Optimizing reactions in continuous flow organic chemistry

Fundamental research in organic chemistry primarily relies on the development of new methods and reagents that exploit specific reactivities, allowing to access to molecular diversity and the properties of a wide range of high-value products. This research involves iterative processes of optimization and selection to maximize yields. These iterative processes are both time-consuming, resource-intensive, and waste-generating, even with new micro/mesofluidic technologies. This is particularly concerning in cases where resources are limited or when toxic, highly active, or unstable compounds are involved.

This new study from Jean-Christophe Monbaliu's laboratory (WEL Research Institute - Uliège) reforms the preparation of high added value compounds in organic chemistry. This innovative approach combines Quantum Chemistry and Artificial Intelligence (DFT-ML), enabling the generation of optimized process conditions within minutes, completely waste-free. In silico conditions are then instructed to an automated lab-scale flow synthesis system, which executes them within record time. In other words, reactions and conditions for which no previous knowledge exists, can be preliminarily modeled without experimentation.

This tool has been successfully applied to electrophilic aminations, a class of reactions particularly relevant to pharmaceutical compound manufacturing. This research holds both fundamental and applied significance, as evidenced by its use in physical organic chemistry to understand reactivity and its application for industrial collaborations. 

Reference : Bianchi et al., Revisiting the Paradigm of Reaction Optimization in Flow with a Priori Computational Reaction Intelligence. Angew. Chem. Int. Ed. (2023) e202311526

Source : Press Release ULiège

Illustration : With autorisation from Jean-Christophe Monbaliu

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