Additively Manufactured Small-Volume Continuous Manufacturing Reactor System for C–C Cross-Coupling Reactions

Continuous manufacturing (CM) is increasingly recognized as a transformative approach in pharmaceutical and chemical production, offering enhanced efficiency, reproducibility, and sustainability compared to conventional batch processing. This study presents the development and application of an additively manufactured PEEK-based small-volume continuous reactor system for the three-stage Suzuki–Miyaura synthesis of biphenyl. The process integrated ligand synthesis, catalyst precursor formation, and the cross-coupling reaction within modular reactors, achieving high product selectivity and reproducibility. Comparative analysis with traditional batch synthesis revealed superior performance for the continuous system, including faster kinetics, shorter residence times, improved yields (up to ~100% for catalyst C within 10 minutes at 100 °C), and reduced waste generation. Additive manufacturing enabled the rapid prototyping of reactors with optimized geometries featuring integrated mixing and heat exchange, ensuring precise control of flow rates and thermal conditions. Beyond pharmaceutical applications, the system demonstrated significant potential for hydrometallurgical processes such as leaching, solvent extraction, and electrochemical metal recovery, where continuous flow operation offers substantial advantages in efficiency and sustainability. These findings underscore the synergy of CM, additive manufacturing, and process analytical technology as a flexible and environmentally responsible platform. The developed reactor system provides a pathway for scalable, modular, and on-demand chemical manufacturing, with broad implications for both high-value drug synthesis and sustainable resource management.