Ready, steady, flow: Pd-loaded hypercrosslinked microreactors for the flow synthesis of paracetamol

We describe the implementation of monolithic polymerised high internal phase emulsions (polyHIPEs) as catalyst supports for the continuous flow synthesis of paracetamol. PolyHIPEs are formed by polymerisation of particle and surfactant-stabilised water-in-oil HIPEs comprising of a divinylbenzene and divinylbenzene/4vinylbenzyl chloride monomer continuous phase. The polyHIPEs were post-functionalised by hypercrosslinking using the Scholl coupling reaction to yield polymers decorated with organophosphorus moieties and surface areas of up to 500 m(2)/g. The phosphorus moieties act as catalyst anchor sites for the subsequent loading of Pd via a Pd-O=P ligand bridge. The Pd-loaded polyHIPEs are used as catalysts for the reduction of 4-nitrophenol to 4-aminophenol, achieving turnover numbers of similar to 2,000. The Pd-loaded polyHIPEs and nonfunctionalised divinylbenzene-based polyHIPEs are fabricated into flow-cells and used en route to Plant-on-aBench as microreactor/mixer for the continuous flow synthesis of paracetamol in yields of 66%.