Micro-Reactor Design for Fast Liquid-Liquid Reactions

Abstract

Continuous operation presents multiple advantages over batch chemistry, yet its usage in the fine chemical and pharmaceutical industry remains limited due to its complexity. A holistic tool-box approach for process development is presented to facilitate technology transfer. Reaction kinetics and reacting phases were taken into consideration for the selection of the most appropriate reactor module and operating conditions. A micro-reactor was then more specifically developed for fast liquid-liquid reactions. The effect of physical properties was investigated in a serpentine micro-reactor using a reactive liquid-liquid extraction and different organic solvents (n-butanol, n-hexanol, MTBE and toluene). The generated droplets yielded a specific interfacial area of 10^4-10^5 m2/m3, compared to ~10^2 m2/m3 with conventional equipment. Two models were developed to predict the mass transfer rates for other reactive systems. Further, the effect of geometry was investigated with five different micro-reactors using either curvature-based or obstacle-based micro-mixers. Curvature-based micro-mixers promoted the undesired parallel flow pattern due to stabilizing centrifugal forces, while obstacle-based micro-mixers avoided it. A scale-up approach was finally proposed on a micro-reactor using an optimized micro-mixer. The mass transfer coefficients in a small-scale (1.5-15 mL/min) and a large-scale (12.5-125 mL/min) systems were compared and demonstrated its validity. The obtained results allowed the prediction, the optimization, and the scaling of performance for liquid-liquid systems in the context of process development from molecular discovery to clinical trials and pilot scale production.