Structure-re activity correlation in Click chemistry: Substituent effect on azide reactivity

An investigation was conducted into substituent effects on azide reactivity during Cu-I-catalyzed click reactions by reacting a variety of model azides with propargyl alcohol in DMF-d(7) using CuBr as catalyst, and monitoring conversions via H-1 NMR. The model azides utilized for this investigation were selected due to structural similarity with the end groups of polymers typically employed in azide-alkyne cycloadditions including polystyrene, poly(methyl acrylate), poly(methyl methacrylate), and polyacrylonitrile. Reactivities of alkyl azides depend on both the electronic properties of the substituent and steric congestion around the end group. The fastest reactions were observed for azides with electron-withdrawing substituents and less sterically congested end groups.