Process Intensification of the Continuous Synthesis of Bio-derived Monomers for Sustainable Coatings using a Taylor Vortex Flow Reactor

We describe the optimization and scale-up of two consecutive reaction steps in the synthesis of bio-derived alkoxybutenolide monomers that have been reported as potential replacements for acrylate-based coatings (Sci. Adv., 2020, 6, eabe0026). These monomers are synthesized by (i) oxidation of furfural with photo-generated singlet oxygen followed by (ii) thermal condensation of the desired 5-hydroxyfuranone intermediate product with an alcohol, a step which until now has involved a lengthy batch reaction. The two steps have been successfully telescoped into a single kilogram-scale process without any need to isolate the 5-hydroxyfuranone between the steps. Our process development involved FTIR reaction monitoring, FTIR data analysis via 2D-visualization and two different photo-reactors (i) a semi-continuous photo-reactor based on a modified rotary evaporator where FTIR and 2D-correlation spectroscopy (2D-COS) revealed the loss of the methyl formate co-product and (ii) our fully continuous Taylor Vortex photo-reactor which enhanced the mass transfer and permitted the use of near-stoichiometric equivalents of O2. The use of inline FTIR monitoring and modelling greatly accelerated process optimization in the Vortex reactor. This led to scale up of the photo-oxidation with an 85% yield and a projected productivity of 1.3 kg day-1, with a space time yield of 0.06 mol day-1 mL-1. Higher productivities could be achieved whilst sacrificing yield; e.g. 4 kg day-1 at 40% yield. The second step, the thermal condensation of 5-hydroxyfuranone, was transformed from a 20 h batch reflux reaction to a < 1 minute thermal flow reaction in a reactor only 3 mL in volume operating at 200 oC with projected productivities of >700 g day-1. Proof of concept for telescoping the two steps was established with an overall two-step yield of 67%, producing a process with projected productivity of 1.1 kg day-1 of the methoxybutenolide monomer without any purification of the 5-hydroxyfuranone intermediate.