Strategy for Rapid and High-Purity Monocyclic Polymers by CuAAC “Click” Reactions

Cyclization of linear polymers by coupling end-groups together to form monocyclic polymers using the very fast Cu-catalyzed azide/alkyne cycloaddition (CuAAC) “click” reaction has been used for many polymer systems. However, the strategy based on the CuAAC methodology has not been guided by theory and relies on the very slow feed of polymer into a highly dilute reaction mixture of solvent and Cu catalyst. This leads to the production of monocyclic polymer in very low concentrations over long periods of time (>10 h) and at high temperatures (>100 °C). In this work we use the Jacobson−Stockmayer theory to predict the % monocyclic polystyrene (c-PSTY) in a one-pot reaction at 25 °C and find from an empirical relationship based on experimental diffusion-controlled rate coefficients for cyclization and condensation of α,ω-polymer chains that the Jacobson−Stockmayer theory is applicable for the CuAAC reaction. This means the % monocyclic can be predicted from theory and is independent of reaction rate parameters (such as catalytic concentration and temperature) and only dependent on polymer concentration. Given this quantitative knowledge, we investigated the effect of l-PSTY concentration, temperature, feed rate, Cu(I)Br concentration, and linear-PSTY molecular weight to find the optimum conditions for the synthesis of monocyclic polymers. It was found that for feed rates greater than or equal to the reaction rate high % monocyclic polymers could be formed. Our strategy allowed us to produce c-PSTY (with 51 monomer units) with high purity (>95%) at a concentration of 1.85 × 10⁻³ M in less than 9 min at 25 °C. This is the highest concentration, shortest time, and lowest temperature, to our knowledge, that anyone has used to obtain macrocycles in high purity by the CuAAC methodology. It also allowed us to develop strategies to produce high % monocyclic from parent l-PSTY with higher molecular weights.