Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

Abstract

Within the “compartmentalised smart factory” approach of the ONE-FLOW project the implementation of different catalysts in “compartments” provided by Pickering emulsions and their application in continuous flow is targeted. We present here the development of heterogeneous Pd catalysts that are ready to be used in combination with biocatalysts for catalytic cascade synthesis of active pharmaceutical ingredients (APIs). In particular, we focus on the application of the catalytic systems for Suzuki–Miyaura cross-coupling reactions, which is the key step in the synthesis of the targeted APIs valsartan and sacubitril. An immobilised enzyme will accomplish the final product formation via hydrolysis. In order to create a large interfacial area for the catalytic reactions and to keep the reagents separated until required, the catalyst particles are used to stabilise Pickering emulsions of oil and water. A set of Ce–Sn–Pd oxides with the molecular formula Ce0.99− xSnxPd0.01O2−δ (x = 0–0.99) has been prepared utilising a simple single-step solution combustion method. The high applicability of the catalysts for different functional groups and their minimal leaching behaviour is demonstrated with various Suzuki–Miyaura cross-coupling reactions in batch as well as in continuous flow employing the so-called “plug & play reactor”. Finally, we demonstrate the use of these particles as the sole emulsifier of oil–water emulsions for a range of oils.

Emulsion Stabilization with Functionalized Cellulose Nanoparticles Fabricated Using Deep Eutectic Solvents

“…Emulsions stabilized by various nano- or microscale particles, offer promising applications in fields that require high stability and low toxicity [ 17 ]. The use of nanoparticles as one tool to capture the enzymes or other catalysts to enhance the formation of Pickering emulsions and improve their catalytic activity have gained interest among researchers [ 18 , 19 , 20 ]. These techniques open new possibilities in applications where the synthesis of highly stable colloidosomes for example through dopamine polymerization can be done in the interfaces of Pickering emulsions [ 21 ].…”

About Solid Phase vs. Liquid Phase in Suzuki-Miyaura Reaction

“…Thus, with concentrations of Pd going from 0.06 to 0.14 mg Pd /L, the TOF leach reached values of 50,000 h −1 (Table 2, entries 10 and 11). Due to Pd redeposition on the support, the use of the catalyst for successive runs or in continuous operation is presented as a good option [56]. A membrane reactor was also used to demonstrate that Pd(0) atoms or Pd(II) ions can leach from Pd nanoparticles during the reaction of 4-iodotoluene with phenylboronic acid at 100 • C [57].…”

Continuous Solid Particle Flow in Microreactors for Efficient Chemical Conversion

“…27 Developing relevant PE catalysis in flow (Figure 1f and g) is attractive from both a catalytic efficiency and a process engineering point of view. 28 Thus, PE as another type of advanced catalytic system that can be applied in biphasic catalytic reactions has promising application aspects in microreactors for delivering a greener and more sustainable chemical synthesis, 29 as demonstrated in the recent work of Vis et al 30 Commercially available or lab-made powder catalysts are usually dispersed on a support for achieving a favorable catalytic activity, the size of which tends to be much larger (e.g., from micrometer to millimeter range). They can be suspended as microparticles in the liquid (e.g., after crushing and sieving to a certain micrometer range) to form a liquid− solid slurry to facilitate their transport and catalysis in microreactors, which allows an easy catalyst separation (by filtration) and extends the versatility of microreactors.…”