Continuous flow synthesis of pyridinium salts accelerated by multi-objective Bayesian optimization with active...

Area of Science:

• Chemical Engineering
• Organic Chemistry
• Computational Chemistry

Background:

• Continuous flow chemistry offers enhanced control and scalability over traditional batch processes.
• Bayesian optimization is a powerful tool for multi-objective experimental design.
• Accurate data analysis, particularly from nuclear magnetic resonance (NMR) spectroscopy, is crucial for reliable chemical synthesis optimization.

Purpose of the Study:

• To implement a human-in-the-loop Bayesian optimization platform (EDBO+) for optimizing butylpyridinium bromide synthesis.
• To simultaneously optimize reaction yield and production rate (space-time yield) under continuous flow conditions.
• To investigate the impact of different data analysis methods on the optimization model's predictions.

Main Methods:

• Utilized a Bayesian optimization platform (EDBO+) for multi-objective experimental design.
• Employed continuous flow reactors for synthesis, enabling precise parameter control.
• Applied the nmrglue Python module for semi-automated NMR data analysis and compared it with manual processing.
• Retrained the EDBO+ model with data from low-field and high-field NMR spectrometers using both analysis methods.

Main Results:

• Successfully generated a Pareto front, optimizing both reaction yield and space-time yield.
• Demonstrated the platform's versatility by expanding the reaction temperature range mid-campaign.
• Showcased the influence of NMR data analysis techniques on the predictive accuracy of the optimization model.
• Extended continuous flow chemistry to synthesize functional materials via quaternization of poly(4-vinylpyridine).

Conclusions:

• EDBO+ effectively optimizes multi-objective chemical syntheses in continuous flow.
• The choice of data analysis method significantly affects Bayesian optimization model performance.
• Continuous flow chemistry, coupled with robust data analysis, provides a scalable and automated route for chemical synthesis and materials development.