The development of PolyHIPE monoliths for use as supports in organic synthesis

Abstract

As part of the ongoing research efforts to discover alternative support materials to polymer beads for use in polymer-supported synthesis, particularly under flow-through, this project involved the synthesis of PolyHIPE (High Internal Phase Emulsion) polymer monoliths. PolyHIPEs containing high loadings of chloromethyl groups were efficiently prepared by the direct copolymerisation of 4-vinylbenzyl chloride and divinylbenzene monomers. As revealed by characterisation of the materials obtained, the VBC monomer hydrolysed to an extent during the polymerisation, replacing a small amount of the chloromethyl functionalities with hydroxymethyl groups. Functionalisation of the PolyHIPEs, in batch and flow-through reactions, produced supports with aminomethyl and hydroxymethyl linkers attached. Conversions were often higher as a result of the flow-through modifications. Capacities were increased further with the introduction of trisaminomethyl and trishydroxymethyl linkers, which showed potential as supports for polymer assisted solution phase (PASP) synthesis and solid phase organic synthesis (SPOS), respectively. Chloromethyl PolyHIPE was shown to be an excellent support for batch and flow-through Suzuki cross-coupling reactions. A remarkably high yield of pure biaryl product was obtained using PolyHIPE in cubic form and an electron-rich boronic acid. In comparison to polymer beads, PolyHIPE was found to be a much more efficient support in both batch and continuous flow modes. PolyHIPE converted a greater amount of chloromethyl groups into biaryl product under identical reaction conditions. Under flow, the channelling effect observed with the beads was completely eliminated with PolyHIPE monoliths. The utility of hydroxymethyl- fianctionalised PolyHIPEs (Wang and tris-OH) in Suzuki coupling reactions was investigated and both showed promise as supports in this application.