Integrating Safety and Efficiency - From Organic Chemistry to Industrial Process

This presentation explores the application of reaction kinetics and physical organic chemistry to process development in the pharmaceutical industry. As a QbD approach, mechanistic understanding through kinetic modeling enables accurate prediction and optimization of complex chemical reactions, addressing key challenges such as reproducibility, scale-up, and safety.

Using benzylation of aniline as a case study, detailed mechanistic identification dramatically improved model accuracy and was utilized in the reaction improvement itself. The models demonstrated excellent extrapolability, enabling prediction under untested conditions and semi-batch optimization with minimal experiments. Moreover, coupled scale-down simulation combining kinetics and heat transfer models was demonstrated for highly exothermic reactions. The fine-tuned heat transfer model achieved highly accurate temperature prediction even in small-scale reactors.

This methodology enables synthetic chemists to leverage mechanistic understanding for reaction development while providing engineers with high-precision models for process design and optimization.