Innovative Approaches to a Scalable Catalytic Flow Reaction: A Focus on Selective Nitro-Group Hydrogenation in a Fixed-Bed System

High Resolution Image Download MS PowerPoint Slide Continuous flow reactions using fixed-bed reactors provide significant advantages in the pharmaceutical synthesis. However, it is still challenging to develop suitable catalysts for flow processes. Conventional Pd- and Pt-based catalysts, the most commonly used in batch reactions, are inappropriate for flow reactions due to their irregular and fine particle sizes and also their chemo-selectivity issues, especially for halogen-substituted nitroarenes. To overcome these limitations, we designed a scalable flow process using a Co/Al 2 O 3 heterogeneous catalyst, which achieved high chemo-selectivity for various nitroarenes, regardless of substituent type or position. The catalyst was supported on uniform spherical Al 2 O 3 carriers with tailored particle size and narrow size distribution, which minimized the reactor pressure drop (Δ P ) and ensured stable operation. In particular, long-term hydrogenation of p -chloronitrobenzene to p -chloroaniline maintained full conversion and high selectivity (>97% at 80 °C) over 180 h with negligible Δ P . This work therefore establishes a robust and versatile catalytic platform for nitro-group hydrogenation, offering industrial relevance for active pharmaceutical ingredient (API) manufacturing.