Evaluation of Sponge Metal Catalysts in a Trickle Bed Reactor for the Continuous Hydrogenation of an Aliphatic Nitro Intermediate

Abstract

Nine sponge nickel catalysts were assessed for the reduction of an aliphatic nitro group in a trickle bed reactor. Focused beam reflectance measurement (FBRM) was used to assess the mechanical strength and particle size distribution of the catalysts. The continuous reduction of (S)-7-methyl-7-(nitromethyl)-1,4-dioxaspiro[4.5]decane was investigated using a Raney nickel catalyst in a fixed bed reactor. The use of a Luna ODiSl temperature probe and an FLIR thermal imaging camera were investigated to monitor the catalyst performance while the process was run. A 1.12 kg sample of the aliphatic nitro compound was reduced to the corresponding amine using a single 20 mL reactor containing 43 g of 3111A Raney nickel over a period of 17 h.

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

“…A comparison of the different methods used in flow hydrogenation is reported in Table 6. This includes a trickle bed reactor (Carangio et al, 2020), a catalytic mixer (Kundra et al, 2021), the H-cube (Irfan et al, 2009), and this work using a slurry conditions. In this case, a reactor of similar size is compared.…”

“…It is the main variable issue as the catalyst may leach and there is a particle migration based on their sizes, leading to a higher pressure drop build up in the reactor (Wu et al, 2003;Li et al, 2004;Wu et al, 2006;Wu et al, 2007). Much work on the deactivation mechanism has been carried out, including investigation towards pressure drop (Quinn 2014) or hydrodynamic (Macdonald et al, 1979) equations, to better understand the technology (Hammond 2017;Carangio et al, 2020). Then, scaling up requires a good understanding of all key parameters (e.g., reactor volume, heat transfer, catalyst size) (Al-Dahhan et al, 1995;Hanusch et al, 2018;Wang et al, 2019).…”

“…A very common practice is the use of a trickle bed reactor (Saroha and Nigam, 1996;Al-Dahhan et al, 1997;Deutschmann et al, 2009) containing a packed bed of catalyst, which the reactants flow through (Gulotty et al, 2018). This is widely used in industry (Perry and Green 2008;Johnson et al, 2012;Rinaldi 2014;Carangio et al, 2020;Fernandez-Puertas et al, 2020), as it allows good control of reaction conditions and simplified scale-up (Jiménez-González et al, 2011;Hickman et al, 2013;Gutmann et al, 2015;Russell et al, 2017;Duan et al, 2020). In this case, the nature and particle size of the catalyst has to be optimized to obtain good results.…”

Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles

“…As we aimed to develop a continuous flow process with a short reactor residence time, direct temperature measurements of our flow reaction were judged to potentially impact on the mixing of reaction components and/or residence times, and we turned instead to thermal imaging of the reactor. This strategy has previously been successfully employed by Ley et al to monitor the exothermic synthesis and decarboxylative dibromination of a glyoxylic acid oxime, 87 and by Williams and co-workers to monitor a Raney nickel catalyst fixed bed reactor, 88 but to our knowledge has not previously been used to study metalation processes or those with reactor residence times under 1 min. Thermal imaging of a flow reaction representative of the conditions shown in table 2, entry 3 revealed a significant exotherm during the reaction, with an increase from rt while pumping solvent alone to ~55 °C (averaged over the whole reactor) or ~70 °C (hottest position on reactor) while the reaction was running, validating our concerns that the reaction was at or near the THF boiling point (figure 2).…”

Evaluation and Screening of Spherical Pd/C for Use as a Catalyst in Pharmaceutical-Scale Continuous Hydrogenations

“…GSK uses a modified ThalesNano H-Cube catalytic reactor of 3 mm internal diameter and HEL FlowCAT catalytic reactors of 6 and 12 mm inner diameters for laboratory-scale process development work. , The internal diameter of GSK’s pilot plant reactors ranges from 25.4 to 50.8 mm. Therefore, the target particle size of the catalysts considered to be used for continuous hydrogenation in reactors with inner diameters ≥6 mm ranges from 50 to 400 μm, where the upper limit is set to ensure a maximum diameter ratio of 15 (Table ) and the lower limit is to avoid getting a high pressure drop.…”