JASON D. WILLIAMS, C. OLIVER KAPPE*
*Corresponding author
Center for Continuous Flow Synthesis and Processing (CCFLOW), Research Center Pharmaceutical Engineering (RCPE), Graz, Austria.
Institute of Chemistry, University of Graz, NAWI Graz, Graz, Austria

Abstract

Catalytic static mixers (CSMs) have recently been developed as hydrogenation catalysts for continuous flow reactor systems. By basing the structure on a 3D-printed metal scaffold, CSMs can be designed to fit flow reactors of any dimensions. The catalytically-active surface can be applied by several different techniques, which provide complementary reactivity and compatibility. Their low catalyst loading, as well as high activity and stability, has already provided a convincing case for certain applications, particularly due to facile scalability. Here, we examine the technology, based on a number of examples from the literature. We aim to highlight the potential of CSMs as an alternative to packed bed reactors, specifically for application in fine chemical and pharmaceutical manufacturing.

INTRODUCTION
Hydrogenation reactions represent a substantial proportion of chemical transformations in a manufacturing environment. Whilst bulk chemical manufacturers are well-accustomed to using continuous processing for this type of reaction, its application in fine chemicals (including the pharmaceutical industry) is far less common. That said, continuous flow hydrogenations have also recently begun to gain traction in the pharmaceutical industry, due to the improved safety profiles, higher productivity for the reactor footprint and simplified catalyst handling (1,2). The majority of applications make use of packed bed reactors (3-6), which are a well-explored reactor type, allowing highly productive hydrogenation reactions in flow. However, these require specific design and detailed testing, regarding their dimensions, particle size, heat transfer, packing character, etc. Even more problematic, is that, in some cases, this optimization process may need to be repeated when moving from lab scale toward pilot and manufacturing. Although this is not always the case, additional planning must be incorporated to ensure that pressure drop on larger scale will ...