“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.

Porous polymer particles—A comprehensive guide to synthesis, characterization, functionalization and applications

“…For the azide bearing beads however, an epoxy monomer was used for the second swelling stage and azide introduction was realized in another step. Although the authors do not mention the reason for the need of another step instead of utilizing an azide monomer for swelling, we believe that it is due to the loss of azide groups during the polymerization of double bonds as recently reported by Perrier et al [359]. We also experienced that azide groups are not only sensitive to temperature but also to UV.…”

Living Radical Polymerization by the RAFT Process - A Second Update

“…MMA [27] 146 [283] S S Ph C 12 H 25 S CO 2 C 2 H 5 tBA [283] 147 [27] S S Ph C 12 H 25 S CO 2 H MMA [27] 148 [335] NIPAM [335] 149 [283] 150 [336,337] S S C 6 H 13 S St [336,337] CMS [336] 151* [338] S S C 12 H 25 S…”

“…Many RAFT agents with azido-functionality (27, 137, 148, 181, 218, 220) or acetylene-functionality (26, 46, 134) have appeared. Ladmiral et al [335] have posted a warning that azides also undergo 1,3-dipolar cycloaddition with common monomers (MMA, MA, NIPAM, and St were studied) and that this can occur under polymerization conditions. The use of lower reaction temperatures in polymerization can minimize this issue.…”

Poly(bromoethyl acrylate): A Reactive Precursor for the Synthesis of Functional RAFT Materials

“…6,53,54 The direct synthesis of polyazides requires polymerization of azido monomers at low temperatures, 55,56 and numerous steps involve handling the toxic and potentially explosive azido derivatives. In our case, 2 equiv.…”