A dynamic acid-base catalytic strategy for enhanced glycerol ketalization via catalytic microenvironment regulation

Ketalization of glycerol is conventionally catalyzed by acids but is generally limited by reaction equilibrium and the low reactivity of hydroxyl groups. Herein, a dynamic acid-base catalytic strategy is proposed by sequentially introducing NaHSO₄ and NaOH into the reaction system. Compared with conventional acid catalysis, the sequential addition of NaOH effectively promoted further ketalization beyond the apparent plateau, significantly enhancing glycerol conversion from 62.5% to 79.3% for the glycerol-acetone system and from 61.9% to 85.4% for the glycerol-butanone system. Conductivity, pH and ¹H NMR analyses suggested that ketalization and base neutralization proceeded simultaneously, resulting in the continuous evolution of the catalytic microenvironment. NaHSO₄ activated the carbonyl group through protonation, whereas the subsequently introduced OH⁻ may regulate the hydrogen-bonding environment of glycerol, thereby facilitating hydroxyl accessibility and reactivity while maintaining sufficient acidity for ketalization. The proposed strategy was further evaluated using various alcohol-ketone substrates and different Brönsted base pairs, supporting its applicability to the investigated reaction systems. This work highlights dynamic catalytic microenvironment regulation as an alternative approach for enhancing reversible ketalization and provides new insights into the design of cooperative acid-base catalytic systems.