One-pot synthesis of alternating poly(ester amide)s via water-regulated esterification and amidation sequence

The synthesis of high-value alternating poly(ester amide)s (PEAs) has traditionally relied on controlled sequential esterifica-tion and amidation reactions. However, the lack of an efficient, straightforward production method has hindered their large-scale manufacture. Here, we demonstrate a one-pot synthesis approach that employs water as an esterification inhibitor to regulate the sequential amidation and esterification of α, ω-amino alcohol and adipic acid. Structural characterization of the amidation intermediates, along with the corresponding PEAs, confirmed the reaction followed the intended pathway. The corresponding equilibrium models were founded based on coexisting systems of hydroxyl, amino, and carboxyl groups, which validated the effectiveness of the method and established its broader applicability. By adjusting α, ω-amino alcohol species, a series of alternating poly(ester amide)s with elevated T_m (92–120 °C) and biodegradable properties were synthesized in a one-pot process. In light of the economic and efficient characteristics of water-regulated sequential condensation, this method shows significant industrial potential for synthesizing high-value biodegradable PEAs with ordered structures.