The use of organo-catalysis in continuous-flow reactor systems is gaining attention in medicinal chemistry due to its cost-effectiveness and reduced chemical waste. In this study, bioactive curcumin (CUM) derivatives were synthesized in a continuously operated microfluidic reactor (MFR), using piperidine-based polymeric networks as catalysts. Piperidine methacrylate and piperidine acrylate were synthesized and subsequently copolymerized with complementary monomers (MMA or DMAA) and crosslinkers (EGDMA or MBAM) via photopolymerization, yielding different polymeric networks. Initially, batch reactions were optimized for the organo-catalytic Knoevenagel condensation between CUM and 4-nitrobenzaldehyde, under various conditions, in the presence of polymer networks. Conversion was assessed using offline ¹H NMR spectroscopy, revealing an increase in conversion with enhanced swelling properties of the polymer networks, which facilitated greater accessibility of catalytic sites. In continuous-flow MFR experiments, optimized polymer gel dots exhibited superior catalytic performance, achieving a conversion of up to 72%, compared to other compositions. This improvement was attributed to the enhanced swelling in the reaction mixture (DMSO/methanol, 7:3 v/v) at 40 °C over 72 h. Furthermore, the MFR system enabled the efficient synthesis of a series of CUM derivatives, demonstrating significantly higher conversion rates than traditional batch reactions. Notably, while batch reactions required 90% catalyst loading in the gel, the MFR system achieved a comparable or superior performance with only 50% catalyst, resulting in a higher turnover number. These findings underscore the advantages of continuous-flow organo-catalysis in enhancing catalytic efficiency and sustainability in organic synthesis.

The development of sustainable catalysts is the main objective in green chemistry approaches. In this study, a catalytically active polymer based on a tertiary amine was synthesized, functionalized with a photo-crosslinker, and structured into nanofibers via electrospinning technique with polycaprolactone (PCL) as a stabilizing additive. Subsequent photo-crosslinking yielded hierarchically porous polymers with high swelling properties and increased surface areas, thereby improving the accessibility of the immobilized catalytically active sites. The nanofiber mats were incorporated into a microfluidic reactor (MFR) setup and utilized as heterogeneous catalysts for the Knoevenagel reaction of malononitrile with different aldehydes. It was observed that the system demonstrated a substantial improvement in NMR yields (40–60%) and turnover frequencies (50–80 h⁻¹) in comparison to catalytical systems that had been previously published. Reusability studies showed reproducibility of NMR yields over up to three cycles. The obtained results demonstrate the potential of electrospun, photo-crosslinked nanofibers as efficient heterogeneous catalysts in microfluidic synthesis, thus contributing to more sustainable production of valuable malononitrile derivatives.