Sustainability and efficiency assessment of vanillin allylation: in solution ball-milling

• Published in: Green chemistry : an international journal and green chemistry resource : GC Vol. 24; no. 2; pp. 7874 - 7882
• Main Authors: Breilly, Damien, Fadlallah, Sami, Froidevaux, Vincent, Lamaty, Frédéric, Allais, Florent, Métro, Thomas-Xavier
• Format: Journal Article
• Published: 18.10.2022
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/d2gc02185d

Allylation of phenols, a widely used reaction in multistep synthetic pathways, was herein investigated using mechanochemistry. This synthesis was first optimized on vanillin by varying key parameters including both chemical ( e.g. , stoichiometry, reaction time) and mechanical ( e.g. , rotational speed, material, size and number of beads, liquid additive) conditions, leading to the isolation of allylated vanillin at the gram scale in excellent yield (95%). The optimized procedure was also successfully implemented to another bio-based phenol of interest, ethyl ferulate (92% isolated yield). The environmental impact of these procedures was compared with more classical in-solution protocols by calculating E factors. When work-up solvents were not taken into account, E factor (sEF) clearly indicated the superiority of the ball-milling approach over the solution-based procedure, underscoring the capacity of ball-mills to drastically reduce the need for "reaction" solvents. On the other hand, when work-up solvents were taken into consideration, E factors (cEF) were in favor of the solvent-based approach, which could be explained by the solvent quantities required to recover the reaction mixture from the ball-mill reactor. Overall, these results highlight (i) the great potential of mechanochemistry to enable the development of both efficient and waste-less allylation of lignin-derived phenolic synthons, and (ii) the need to study higher-scale and continuous mechanochemical processes, such as by using extruders, to further improve efficiency and sustainability of such mechanochemical processes. Allylation of phenols, a widely used reaction in multistep synthetic pathways, was herein investigated using mechanochemistry and compared to more conventional synthesis in solution.