Optimisation of azide–alkyne click reactions of polyacrylates using online monitoring and flow chemistry

Abstract

Herein, the online and inline ¹H-NMR monitoring of azide–alkyne click reactions of polymers is investigated. The effect of the reaction solvent, ligand and temperature were investigated on small “model” molecules. Azidopropanol and 3-azidopropyl-2-bromoisobutyrate were used as the azide-containing molecules, whereas propargyl alcohol was chosen as the alkyne reactant. The optimal conditions were found to be dimethylsulfoxide (DMSO) as solvent with 2,2′ bipyridine as ligand, which were subsequently employed in the modification of different azide-functionalised polyacrylates with propargyl alcohol. From this, poly(methyl acrylate) was chosen to investigate the more complex conjugation of an alkyne monosaccharide. Finally, the “click” reaction was performed in flow leading to a successful modification in less than 1 h.