Sustainable production of active pharmaceutical ingredients from lignin-based benzoic acid derivatives via “demand orientation”

Research related to lignin valorization into fine chemicals is an extremely demanding task due to the wide distribution and low economic value of depolymerization products. Benzoic acid derivatives (BADs) are the final products of the selective oxidation of the lignin side chain (i.e., p-hydroxybenzoic acid, vanillic acid, syringic acid, and benzoic acid), with favorable processibility functionality, showing great potential in the synthesis of active pharmaceutical ingredients (APIs) containing ester and carbonyl groups. Herein, this tutorial review presents our views on lignin utilization, especially using lignin-based benzoic acid derivatives (LBADs) as raw materials for the synthesis of APIs, with the aim of providing a greener, more eco-friendly approach for providing a sustainable route for the production of APIs. We first introduce the conversion of lignin or lignin platform compounds via the oxidative cleavage of C-C and C-O bonds to LBADs. Subsequently, focusing on the functional group modification strategy for the conversion of LBADs, we raise a “Demand Orientation” concept and several typical API synthesis routes. This tutorial review provides green production routes from LBADs in six instances (i.e., trimebutine, aniracetam, diethylstilbestrol, dopamine, acetaminophen, oxybuprocaine). Finally, several others APIs from LBADs via theoretically feasible and sustainable routes are proposed. Some personal perspectives are provided to highlight the opportunities within this attractive field. © 2023 The Royal Society of Chemistry.