Intensified,\nKilogram-Scaled, and Environment-Friendly:\nChemoenzymatic Synthesis of Bio-Based Acylated Hydroxystyrenes

Lignin-derived styrene derivatives are versatile building\nblocks\nfor the manufacture of biobased polymers. As shown previously, phenol-protected\nhydroxystyrenes are accessible under industrially sound conditions\n(>100 g L<sup>–1</sup>, >95% yield) by subjecting biogenic\nphenolic acids to enzymatic decarboxylation and base-catalyzed acylation\nin nonaqueous media (wet cyclopentyl methyl ether, CPME). Herein,\nwe demonstrate the production of 1 kg of 4-acetoxy-3-methoxy-styrene in a 10 L reactor and present practical\nadjustments to the up- and downstream processing that warrant a straightforward\nprocess and high isolated yields. Additionally, an environmental assessment\nis conducted, starting with a thorough <i>E</i> factor analysis\nto identify the sources that contribute most to the environmental\nburden (solvent and downstream processing). Also, the total CO<sub>2</sub> production of the process is studied, including contributions\nfrom energy use and the treatment of generated wastes. The energy\nimpact is evaluated through thermodynamic analysis, and the environmental\nfootprint contributions by wastes–organic and aqueous fractions–are\nassessed based on CO<sub>2</sub> emissions from solvent incineration\nand wastewater treatment, respectively. Overall, the holistic assessment\nof the process, its optimization, scale-up, product isolation, and\nenvironmental analysis indicate the feasibility of multistep chemoenzymatic\nreactions to deliver high-volume, low-value chemicals from biorefineries.