Continuous Reactor Cascades: an Efficient Toolbox toward Tailor-Made Polymer Materials

Abstract

Continuous flow processes – an innovative alternative for conventional batch operations – are associated with high control over the reaction parameters, fast heat exchange, high reaction efficiencies and easy scalability. In combination with controlled/”living” polymerization techniques, the polymer field can benefit significantly from microreactor technology. Different polymerization techniques (anionic, cationic, free radical, ATRP, NMP, RAFT, …) were already investigated under continuous conditions. The research in this thesis focused on the development of continuous reactor cascades as an efficient toolbox towards tailormade polymer materials. Hence, based on the beneficial features of microreactor technology (MRT), different polymerization techniques were employed to synthesize complex polymer materials for future biomedical applications. Divided into five separate research projects, five different reactor set-ups were designed and developed depending on the goal of the project. Complex macromolecular structures based on poly(2-oxazoline)s have been targeted on a small scale by investigating the cationic ring-opening polymerization of 2-oxazolines in a continuous microflow reactor. The homopolymerizations of 2-ethyl-2-oxazoline and 2-n-propyl-2-oxazoline were investigated, aiming for full monomer conversions. Also well-defined diblock and triblock copolymers were produced in a microfluidic reactor cascade (Figure 8.1), demonstrating the high potential of continuous flow chemistry for precision synthesis of complex macromolecules such as block copolymers. (Chapter 2) In a second project, the anionic ring-opening polymerization of cyclic phosphates and a direct postmodification step have been investigated towards the synthesis of functional poly(phosphoester)s. Therefore, the homopolymerization of 2-isobutoxy-2-oxo-1,3,2-dioxaphospholane (iBP) has been optimized. After optimization, 2-butenoxy-2-oxo-1,3,2-dioxaphospholane (BP) with an alkene functionality in the side chain was polymerized and directly post modified via a UV-induced radical thiol-ene reaction in a two-stage microfluidic cascade (Figure 8.2) with a high efficiency. (Chapter 3) An upscalable method was investigated for the multiblock copolymer production via reversible addition-fragmentation chain transfer (RAFT) polymerization in a fully continuous multireactor cascade. Theoretic calculations were carried out to target full monomer conversion in order to avoid copolymer formation. A broad variety of homo-, diblock, triblock and tetrablock copolymers was obtained. This procedure is thus extremely useful for high-throughput experimentation. Moreover, the reactor allows for facile upscaling of the reactions: the tetrablock copolymer PnBuA-b-PMA-b-PEA-b-PtBuA was obtained in quantities of 150 g in 26 h, illustrating the high potential of continuous flow processes for the production of high-value polymer materials (Figure 8.3). (Chapter 4) Next, an enzyme-immobilized reactor has been developed to carry out continuous enzyme-catalyzed radical polymerizations.(Chapter 5) Finally, cyclic polymers were prepared via a ring-closure strategy in a looped flow reactor. The preparation of cyclic polymers via the ring-closure strategy requires highly diluted reaction solutions (< 0.1 g L -1) to avoid intermolecular side reactions. To overcome this limitation, a looped flow reactor was developed whereby the polymer precursor was gradually added via an injection pump. The polymer precursor was directly diluted by the solvent/cyclic polymer mixture, which recirculates through the recycle loop via the use of a loop pump. This looped flow reactor was then employed to carry out the intramolecular coupling of a synthesized α,ω-functionalized linear polymer precursor, yielding the targeted cyclic polymer (Figure 8.5). (Chapter 6)

Continue flow-processen vormen een innovatief alternatief voor conventionele batch-procedures. Continue flow-processen hebben dan ook heel wat voordelen, zoals een goede controle over de reactieparameters, een efficiënte warmteoverdracht en een eenvoudige (op)schaalbaarheid. In combinatie met gecontroleerde/ levende polymerisatietechnieken hebben continue flow-processen heel wat te bieden voor het polymere vakgebied. Verschillende polymerisatietechnieken (anionisch, cationisch, vrij radicalair, ATRP, NMP, RAFT) zijn al eerder onderzocht in continue flow-reactoren. Het onderzoek in deze thesis focust op het ontwikkelen van een continue flow reactorcascade voor de synthese van specifieke polymere materialen voor biomedische toepassingen. Verdeeld in vijf aparte onderzoeksprojecten werden er dan ook vijf verschillende reactoropstellingen gebruikt. Complexe polymere materialen, zoals blokcopolymeren van poly(2-oxazoline)s, werden doelgericht gesynthetiseerd op kleine schaal door gebruik te maken van een continue flow reactorcascade (Figuur 8.1) (Hoofdstuk 2). Directe postmodificatiereacties werden onderzocht voor de synthese van functionele poly(fosfoëster)s (Figuur 8.2) (Hoofdstuk 3). Een opschaalbare productiemethode werd onderzocht voor het aanmaken van multiblokcopolymeren (Figuur 8.3) (Hoofdstuk 4). Een enzyme-geïmmobiliseerde reactor werd ontwikkeld en getest voor enzyme-gekatalyseerde radicalaire polymerizaties (Figuur 8.4) (Hoofdstuk 5). Tenslotte werd er ook een ‘looped’ reactor ontwikkeld om cyclische polymeren te maken (Figuur 8.5) (Hoofdstuk 6).