Microwave-assisted flow processing in heterogeneously copper nano-catalyzed reactions

Abstract

In the last decades, micro-processing and microwave technology have been established as mature technologies, however, mainly instigated by academia. Many advances in micro-process technology have led to novel routes and/or process windows to replace batch operations by more efficient continuous processes, both at lab and at industrial scales. Especially, the fine-chemicals industry has been recognized for realistic implementation of these technologies with respect to both scale as well as cost. In this thesis, the major hurdles to combine microwave and micro-processing technology for organic syntheses have been addressed. In comparison to gas-phase reactions, metal-catalyzed liquid-phase organic synthesis requires different operational process windows to realize successful implementation of micro-processing. Major issue here is to avoid solid bases and slurry catalysts by including pre-treatment steps and depositing catalysts onto structured supports. In addition, the use of metals as catalysts under microwave irradiation is known for rapid energy absorption and, therefore, requires special attention regarding temperature control. The Ullmann-type coupling reaction and the Simmons-Smith type cyclopropanation are both intensively employed in the fine-chemicals industry and were, therefore, investigated over various novel heterogeneous Cu catalysts in this project. The Cu-catalyzed coupling of aromatic compounds is not only an excellent example to investigate the benefits of integrated microwave and micro/milli-reactor technologies, but also for its potential applications in the production of pharmaceutically active molecules, such as antivirals and antibiotics (e.g. Vancomycin). This type of organic reactions provides considerable challenges to overcome, both with respect to the severe reaction conditions and, undoubtedly, the sustainability of heterogeneous catalysis which substantially contributes to the cost in flow processing. More importantly, however, was the use of heterogeneous CuZn nano-colloids which, as oxidative stable metallic microwave-absorber, provide an additional benefit (but also point of attention) regarding the higher temperatures at the locus of the reaction. Therefore, monometallic and bimetallic Cu-based nanoparticles with a narrow size-distribution and a high resistance against oxidation and agglomeration were developed. The chemical and colloidal stability of these Cu-based nanoparticles, including their purity and morphology, could be significantly improved by coating the copper nanoparticles with poly(N-vinylpyrrolidone). These nano-catalysts were then tested for their performance in the Ullmann-type coupling reaction and the Simmons-Smith cyclopropanation. Subsequently, these novel nano-catalysts were immobilized onto a microwave-transparent TiO2 support and used in a fixed-bed reactor. Novel routes for the preparation of highly active TiO2-supported Cu and CuZn catalysts were proposed and applied in Cu-catalyzed organic reactions. The copper oxidation was significantly suppressed by using CuZn/TiO2 catalytic films and a strong relation between the catalyst composition and activity was found for the Ullmann C O coupling reaction. This novel preparation method was based on titania dip-coating onto glass beads, obtaining either structured mesoporous or non-porous titania thin films, which could be loaded with the catalyst nanoparticles by deposition onto the calcined films. These catalysts were analyzed using various characterization techniques and in operando synchrotron X-ray absorption spectroscopy, giving a better understanding of their catalytic behavior. Besides catalyzing a reaction, the energy supply towards the catalyst surface is obviously as important and has been also investigated in this project. This issue has been addressed separately, because in traditional reactors the energy supply is particularly governed by classical heat transfer limitations. Furthermore, the troubleshooting of the major obstacles for continuous operations to synergize the benefits of microwave systems and micro/milli-processing in flow synthesis has been targeted. A micro fixed-bed reactor was designed, using packed spherical glass beads coated with the catalyst and support, for kg-scale flow operations in the Ullmann C-O coupling. In addition, the influence of reactor shape and dimensions for effective microwave irradiation was studied. Experimental evidence of complete microwave penetration in the radial direction was found, allowing rapid and controlled heating without significant radial temperature gradients in the flow-through reactors. The above mentioned developments in chemistry, nano-catalysis and reactor engineering were the basis for an extended cost study, consisting of 14 process scenarios. In this way, the cost-impact of micro-processing and microwave heating for liquid-phase reactions in fine-chemicals synthesis could be envisaged. Two examples were studied, i.e. the Ullmann-type coupling reactions and the Aspirin synthesis. It could be concluded that the operating costs in the Ullmann-type processes compared to those of the Aspirin synthesis can be defined as either material based (e.g. reactant excess, pretreatment and catalyst synthesis) or downstream processing based (e.g. work-up, waste treatment) processes. The impact of integrating microwave heating and micro-processing systems on profitability was evaluated with respect to operational costs and chemical productivity. This techno-economic evaluation provided a route map, highlighting feasible routes to combine different technologies, chemical processes and catalyst systems.