Optimization techniques for carbodiimide activated synthesis of poly((RS)-3,3,3-trifluorolactic acid); statistically designed experiments to optimize polymerization conditions

Poly((RS)-3,3,3-trifluorolactic acid) was synthesized from the alphahydroxy acid, (RS)-3,3,3-trifluorolactic acid, by esterification with 1,3-diisopropylcarbodiimide condensing agent and catalytic salts of 4-(dimethylamino)pyridine and protic acids. Literature data of related esterification chemistry indicated that temperature, solvent, and catalyst can affect the polymerization chemistry. Optimization of polymer product yield was desirable to understand better how to control the reaction as well as producing high molecular weight polymer in sufficient quantity for subsequent characterization. The goals of this study were to maximize the polymer yield and molecular weight through the use of statistically designed polymerization experiments. A D-optimal design was developed for the completion of this study. Two different solvents and catalysts were investigated. Also, the level of catalyst was varied. As a result of this experimental design study, optimum conditions for highest product yield and molecular weight (indicated by solution viscosity) were identified. Response surface plots show that polymerization in methylene chloride at 5–7°C with the catalytic salt 4-(dimethylamino)pyridinium 4-toluenesulfonate (DPTS) at fractional molar equivalent (with respect to monomer) quantities provided polymer consistent with the study objectives.