Reevaluating Lithium Chloride as a Safer Catalyst for Polylactide Synthesis: A Toxicological and Process Perspective

We report a reinvestigation of lithium chloride (LiCl) as a catalyst for the ring-opening polymerization (ROP) of l-lactide, using octa(ethylene glycol) dimethyl ether (EG8) as a coordinating agent. Although conducted under inert atmosphere, the presence of trace water does not impair polymerization efficiency, eliminating the need for high-vacuum techniques or aggressive drying protocols. Water initiates the reaction via in situ formation of HO-Li+ species, which generate lithium lactate, the actual active species in the system. The Li+ coordination environment, modulated by EG8, governs both reactivity and stereocontrol, with prolonged reaction leading to partial epimerization of l-lactide into meso-lactide. The process proceeds with excellent control, as evidenced by narrow dispersities and linear Mn evolution, until interchain condensation occurs. Beyond this, the system enables polymerization from nonrecrystallized l-lactide and activates alcohol-based co-initiators such as 1-pyrenemethanol with quantitative end-group incorporation. This work provides mechanistic insight into LiCl-catalyzed ROP and highlights a safer, function-oriented approach to PLA synthesis under sustainable conditions.