Continuous Hydrogenation: Triphasic System Optimization at Kilo Lab Scale Using a Slurry Solution

Abstract

Despite their widespread use in the chemical industries, hydrogenation reactions remain challenging. Indeed, the nature of reagents and catalysts induce intrinsic safety challenges, in addition to demanding process development involving a 3-phase system. Here, to address common issues, we describe a successful process intensification study using a meso-scale flow reactor applied to a hydrogenation reaction of ethyl cinnamate at kilo lab scale with heterogeneous catalysis. This method relies on the continuous pumping of a catalyst slurry, delivering fresh catalyst through a structured flow reactor in a continuous fashion and a throughput up to 54.7 g/h, complete conversion and yields up to 99%. This article describes the screening of equipment, reactions conditions and uses statistical analysis methods (Monte Carlo/DoE) to improve the system further and to draw conclusions on the key influential parameters (temperature and residence time).

Process intensification of the catalytic hydrogenation of squalene using a Pd/CNT catalyst combining nanoparticles and single atoms in a continuous flow reactor

“…Micropacked bed reactors have been successfully demonstrated [42,43] for such 3-phase operations but were operated with larger particles (10-100µm), and prohibitive pressure drops are expected with this catalyst. "Slurry Taylor flow", already mastered in our group [44][45][46], can be envisaged as an advantageous contacting mode, but its scalability remains unsolved.…”

Continuous Solid Particle Flow in Microreactors for Efficient Chemical Conversion

“…The beneficial gas–liquid hydrogenation over slurry catalysts has also been demonstrated in Corning advanced-flow microreactors with the hydraulic diameter of fluidic channels around 1 mm. − The enhanced heat and mass transfer in microreactors enabled a drastic reduction of the required reaction time for the desired conversion to below 2 min (versus >10 h in batch), as shown for the highly exothermic hydrogenation of a pharmaceutical compound over a noble metal slurry catalyst . Furthermore, the slurry hydrogenation of ethyl cinnamate to ethyl 3-phenylpropanoate (as a pharmaceutical intermediate or used in organic synthesis) in this type of microreactor was tested . Using the commercial Pd/C catalyst in a stable slurry form (in ethanol), a high yield (98%) of ethyl 3-phenylpropanoate was obtained in the microreactor at 75 °C in 18 s, corresponding to a productivity of 51.3 g/h (in contrast to 27.8 g/h at 25 °C) (Table , entry 2).…”

“…90 Furthermore, the slurry hydrogenation of ethyl cinnamate to ethyl 3-phenylpropanoate (as a pharmaceutical intermediate or used in organic synthesis) in this type of microreactor was tested. 91 Using the commercial Pd/C catalyst in a stable slurry form (in ethanol), a high yield (98%) of ethyl 3-phenylpropanoate was obtained in the microreactor at 75 °C in 18 s, corresponding to a productivity of 51.3 g/h (in contrast to 27.8 g/h at 25 °C) (Table 2, entry 2). However, the yield decreased to 93% in 30 s, which was ascribed to the nonoptimal mixing of the gas−liquid−slurry mixture leading to lower heat/mass transfer rates.…”

Copper-Catalyzed Continuous-Flow Transfer Hydrogenation of Nitroarenes to Anilines: A Scalable and Reliable Protocol

“…Hydrogenation reactions are among the most important reactions in pharmaceutical industry API synthesis and make up more than 10% of all chemical transformations . Precious-metal-catalyzed hydrogenation is the most frequently used procedure, and great effort has been invested in developing appropriate protocols and catalysts for its industrial-scale use. − The performance of hydrogenation reactions under flow chemistry has improved considerably in recent times thanks to significant advances in efficiency, safety, and environmental impact. , Flow approaches provide better gas–liquid contact than traditional hydrogenation approaches, which are limited by the rate of hydrogen gas diffusion into the bulk solvent. , Due to this, flow chemistry is well suited for use in reduction chemistry because of the inherent risks involved in such transformations . While hydrogen gas or hydride act as the reducing agents in most cases, the in-line production of hydrogen is possible when using smart systems, which also allow mild reaction conditions to be employed. , Nevertheless, the use of hydrogen gas is undesirable in industrial applications, as it entails the use of specialized and expensive equipment.…”