“Click” Chemistry and Radical Polymerization: Potential Loss of Orthogonality

Abstract

The noncatalyzed cycloaddition of azides with electron-poor olefins was investigated in conditions mimicking those of living radical polymerization. The pathway of this reaction was investigated, and model reactions were designed to study this reaction with various types of monomers (N-isopropylacrylamide, dimethylacrylamide, methyl acrylate, methyl methacrylate, and styrene). We found that the azide undergoes 1,3-cycloaddition with the double bond of these monomers, in the absence of catalyst, at high temperatures (60 °C) and for long reaction times. This side reaction can be of dramatic significance as it impairs the orthogonality of copper-catalyzed azide−alkyne cycloaddition (“click chemistry”); short polymerization time and low temperatures should be targeted to limit these side reactions.