p-Hydroxycinnamic acids are key intermediates for the synthesis of a wide range of active molecules (antioxidants, anti-UV, renewable polymers and resins1,2). However their industrial application is limited by the costly separation and purification steps needed to extract them from raw biomass. The main synthetic route to p-hydroxycinnamic acids consist in the condensation of malonic acid with phenolic aldehydes through Knoevenagel reaction. Usually, Knoevenagel reactions are performed with a large amount of pyridine as solvent and with aniline or piperidine as catalyst2. Pyridine is toxic and may induce serious health damage. Although aniline and piperidine are less dangerous nevertheless it is preferable to reduce their utilization. Few alternatives have been described in the literature. Ionic liquids exhibiting high solubility and recyclability represent one of them3. However, industrial applications are compromised due to their cost. Microwaves were also investigated and allow reducing significantly the reaction time4. Several examples of aldol condensation of ketone using proline as an alternative to the petro-sourced catalysts are described in the literature. Most recently, proline was combined with MgO allowing access to excellent condensation yields5. However, no example was found for Knoevenagel condensation with acids. The implementation of this strategy to such reaction has been investigated for the synthesis of p-hydroxycinnamic acid. The influence of each parameter (equivalent of malonic acid, equivalent of proline, equivalent of MgO, concentration and temperature) on the Knoevenagel reaction has been evaluated thanks to a design of experiment. The optimal conditions proposed by the software were tested and validated. Finally, the Knoevenagel condensation of malonic acid with various p-hydroxybenzaldehydes was performed allowing the access to different p-hydroxycinnamic acids. Sinapic, ferulic and caffeic acids were thus isolated in good yields (~ 80%).

Sustainable p-hydroxycinnamic acids synthesis through proline-mediated Knoevenagel reaction

2019 Spring National Meeting

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