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

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

Continuous microreactor processing, reactive ionic liquids and microwave heating - approaches towards intensified Kolbe-Schmitt synthesis

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Process intensification of the Kolbe-Schmitt synthesis by application of reactive ionic liquids and microwaves

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Microwave-assisted Cu-catalyzed Ullmann ether synthesis in a continuous-flow milli-plant

The combination of milli-scale processing and microwave heating has been investigated for the Cu-catalyzed Ullmann etherification in fine-chemical synthesis, providing improved catalytic activity and selective catalyst heating. Wall-coated and fixed-bed milli-reactors were designed and applied in the Cucatalyzed Ullmann-type CAO coupling of phenol and 4-chloropyridine. In a batch reactor the results show clearly increased yields for the microwave heated process at low microwave powers, whereas high powers and catalyst loadings reduced the benefits of microwave heating. Slightly higher yields were found in the Cu/ZnO wall-coated as compared to the Cu/TiO2 fixed-bed flow-reactor. The benefit here is that the reaction occurs at the surface of the metal nanoparticles confined within a support film making the nano-copper equally accessible. Catalyst deactivation was mainly caused by Cu oxidation and coke formation; however, at longer process times leaching played a significant role. Catalyst activity could partially be recovered by removal of deposited by-product by means of calcination. After 6 h on-stream the reactor productivities were 28.3 and 55:1 kgprod=ðm3 R hÞ for the fresh Cu/ZnO wall-coated and Cu/TiO2 fixed-bed reactor, respectively. Comparison of single- and multimode microwaves showed a threefold yield increase for single-mode microwaves. Control of nanoparticles size and loading allows to avoid high temperatures in a single-mode microwave field and provides a novel solution to a major problem for combining metal catalysis and microwave heating. Catalyst stability appeared to be more important and provided twofold yield increase for the CuZn/TiO2 catalyst as compared to the Cu/TiO2 catalyst due to stabilized copper by preferential oxidation of the zinc. For this catalyst a threefold yield increase was observed in single-mode microwaves which, to the best of our knowledge, led to a not yet reported productivity of 172 kgprod=ðm3 R hÞ for the microwave and flow Ullmann CAO coupling

Intensification of the capillary-based Kolbe-Schmitt synthesis from resorcinol by reactive ionic liquids, microwave heating or a combination thereof

The continuous Kolbe-Schmitt synthesis of 2,4-dihydroxybenzoic acid from resorcinol was carried out using a setup with a capillary reactor of mm-internals and a micro heat exchanger. The process intensification potential of microwave irradiation for heating up the reactant solution and/or of using ionic liquids as carbonating reactants was evaluated. For the Microwave assisted Aqueous Kolbe-Schmitt synthesis (MAKS), power-to-temperature graphs were calibrated with water and real-case (ion-containing) solutions, revealing several features relevant for process control. Due to higher mean reaction temperatures inside the reactor thanks to faster heating, the yields of all MAKS experiments were higher as compared to the Conventionally Heated (oil bath) aqueous Kolbe-Schmitt synthesis (CHKS) without use of microwave irradiation. The highest yield (before isolation and purification) obtained by MAKS was 52% (at 160 °C, 8 bar, 1 L/h, 90 s), exceeding the yield of CHKS by 5% (at 140 °C, 40 bar, 84 mL/h, 390 s) at a concurrent reduction of reaction time. The MAKS productivity, although lower than possible due to setup limitations (large internal volumes), was up to 67 g/h being in the same range as the CHKS productivity from 25 g/h (39%, 43 s) to 86 g/h (34%, 11 s). Two solutions of ionic liquids were used as CO2 donating agents, a diluted (1.57 mol/L) and concentrated one (3.2 mol/L) with ethyl based methyl imidizoalium hydrogen carbonate (EMIMHC) and a concentrated one (2.7 mol/L) with butyl based methyl imidizoalium hydrogen carbonate (BMIMHC). The yield obtained for the ethyl based ionic liquid (e-CHILKS) operation was 44% (at 180 °C, 35 bar, 0.17 L/h, 130 s) at a productivity of 5.9 g/h. The yield of b-CHILKS was 59% under the same conditions, yet with a higher productivity of 14.2 g/h. For the Microwave assisted butyl Ionic Liquid Kolbe-Schmitt synthesis (e-MILKS) a yield of 58% at a productivity of 25.3 g/h was derived

Nanoparticulate copper - Routes towards oxidative stability

A modified polyol-based reduction method in ethylene glycol that incorporates poly(N-vinylpyrrolidone) (PVP, Mav = 10000; 40000; 55000) as polymeric anti-agglomerant alongside a reducing additive (N2H4·H2O, NaBH4, NaH2PO2·H2O) has been employed to investigate the influence of synthetic parameters on the purity, morphology and stability of an array of polymer-coated copper nanoparticles. While data point to ethylene glycol being capable of acting as a reductant in this system, the use of NaH2PO2·H2O as co-reductant in tandem with the presence of PVP (Mav 40000) has rendered nanoparticles with a mean size distribution of 9.6 ± 1.0 nm that exhibit stability towards oxidation for several months. These data allow us to probe fundamentally how oxidatively stable nano-copper might be achieved