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Proline-Mediated Knoevenagel–Doebner Condensation in Ethanol: A Sustainable Access to p-Hydroxycinnamic Acids

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Naturally occurring p-hydroxycinnamic acids were obtained using an amine-and toxic solvent-free Knoevenagel-type pathway. This method uses not only non-toxic reagents (i.e., L-proline and magnesium oxide as catalyst) and ethanol as… Click to show full abstract

Naturally occurring p-hydroxycinnamic acids were obtained using an amine-and toxic solvent-free Knoevenagel-type pathway. This method uses not only non-toxic reagents (i.e., L-proline and magnesium oxide as catalyst) and ethanol as green solvent, all reagents and solvent being renewable and accessible at low price. By combinaing a Design of Experiment and a One Variobale At a Time optimization (OVAT), the different reaction parameters optimized in order to favor sinapic acid synthesis over that of the two other possible by-products, the corresponding di-acids and vinyl phenols. This alternative to classical Knoevenagel reaction allowed to substitute traditional pyridine-and piperidine-catalyzed pathway while obtaining each natural p-hydroxycinnamic acids in good conversions and yields (50-85%).

Keywords: ethanol; knoevenagel doebner; hydroxycinnamic acids; proline mediated; mediated knoevenagel; knoevenagel

Journal Title: ACS Sustainable Chemistry & Engineering
Year Published: 2019

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