From batch to continuous manufacturing: Design, feasibility evaluation and test of a continuous tubular Microfibrous Entrapped Catalyst Reactor for highly energetic three-phase catalytic reactions in the manufacture of fine chemicals and pharmaceuticals

Abstract

The production of fine chemicals and pharmaceuticals has, until the present day, been predominantly carried out in batch processes, that are often constrained by the limitations of traditional batch reactors, which suffer from poor heat management, slow mass transfer, and inefficient mixing. These limitations translate to long cycle times, inefficient energy usage, and high operational costs, issues that are particularly critical in processes that involve highly energetic, multiphase reactions, forcing manufacturers to limit throughput and productivity. As industries seek to improve efficiency, continuous processing has emerged as a promising alternative, offering potential benefits such as higher product quality, reduced footprint, increased safety, and shorter development times. This dissertation explores the design and implementation of a novel continuous multiphase catalytic reactor using MicroFibrous Entrapped Catalysts (MFEC), aiming to address the operational and economic challenges associated with batch processing. To this aim, a combination of empirical and experimental methods was employed to evaluate the MFEC reactor's economic feasibility, and its performance in terms of heat transfer, mass transfer, and mixing characteristics. The work is based on three main pillars. First, a comprehensive economic analysis was conducted, calculating capital expenditure (Capex), operational expenditure (Opex), and total costs of manufacturing, using empirical correlations and comparing the results against traditional batch setups. Under this approach, important characteristics of the process’ design are considered and evaluated, among them the total production demand, the availability of equipment, the costs of raw materials, and the extension of the life of the chosen catalyst. By examining different scenarios relevant to real industrial manufacturing environments, the main economic drivers of these processes are revealed, and the grounds for the development of novel processes that are attractive to manufacturers are set. Next, an evaluation of fundamental fluid dynamics characteristics within Microfibrous Entrapped Catalyst reactors is performed, measuring liquid holdup, pressure drop, and liquid residence time distributions, to elucidate the basic phenomena that promote intimacy of three phase contacting in heterogeneous catalytic reactions where a reactant gas is sparingly soluble in a liquid phase containing a co-reactant as wetted into a solid catalyst particulate. Through experimentation, unique aspects of the MFEC structure are revealed, linked to the surface tension forces experienced by the liquid within the small pores of the catalyst bed, that provide a distinct phase contacting dynamic heretofore not observed in other traditional reactor morphologies. Finally, to prove the feasibility of using MFEC technology for the proposed applications, experiments were conducted using the three-phase catalytic hydrogenation of a nitro compound dissolved in a liquid solvent, with gaseous nitrogen over a Palladium-supported catalyst as a probe reaction using a MFEC reactor built at laboratory-scale. The effects of gas flowrate, temperature, catalyst loading and initial key reactant concentration on conversion, thermal management and catalyst activity were examined, with the objective of putting the potential benefits of the novel design to the test under real reacting conditions as those used in industrial manufacturing processes. The results suggest that continuous manufacturing using MFEC reactors could yield significant savings of up to 75% in both Capex and Opex while improving process performance, being the catalyst activity maintenance the principal economical driver to make the proposed process feasible for implementation as a viable alternative to batch. Experiments demonstrated improved and distinct phase fluid dynamics where gas and liquid can move nearly independently over a wide range of superficial velocities, with higher liquid holdups, lower pressure drops, and narrower liquid residence time distributions than other reactor designs. Finally, proof-of-concept experiments highlighted the potential of the MFEC reactor as a viable alternative for performing catalytic hydrogenations and other classes of three-phase reactions, even though limitations in the particular probe reaction chosen and the prepared catalyst were evident. These results underscore the potential of MFEC technology to revolutionize chemical production by introducing an economically feasible process capable of providing precise temperature control, higher catalytic effectiveness, and optimized residence time distributions in complex multiphase systems. This work contributes to the broader effort from both academia and industry to transition from batch to continuous manufacturing, offering scalable, safer, and more efficient alternatives for fine chemicals and pharmaceuticals production. Each chapter of this dissertation was originally written with the intention of peer reviewed publication. While some of the information on the background or experimental methods in individual sections may repeat for a reader exploring this document as a whole, the aim was to provide a substantial context for each part of the story in the individual publications.