Sustainable one-pot production of lignin-based bioactive quinazolinone derivatives

Abstract

Nitrogen-participated catalytic conversion of lignin into high value-added N-heteroaromatic chemicals, rather than aromatic compounds composed primarily of C, H, and O, is of great importance to cost-effective biorefinery. Herein, a bifunctional I₂-promoted oxidation strategy has been proposed for one-pot synthesis of quinazolinone derivatives under ambient atmosphere, utilizing lignin β-O-4 moieties as the substrates and 2-aminobenzamide as the nitrogen source. This direct synthesis protocol sufficiently exploits the C_β or C_γ atoms to produce desirable derivatives instead of by-products. Experimental and DFT results confirm an integral multistep cascade transformation involving the activation of CO bonds by Lewis acid I₂, sequential amide-participated C–N bonds formation together with N-heteroaromatic ring construction, and oxidative cleavage of C_α-C_β bonds to generate quinazolinone derivatives and phenyl formate, driven by air or I₂/DMSO synergistic oxidation, followed by further oxidation of phenyl formate to yield quinazolinone. Notably, this strategy is effective in converting the oxidized birch lignin into the corresponding desired quinazolinones with a total yield up 25.9 wt%. Interestingly, among the products, 2-(4-hydroxy-3,5-dimethoxyphenyl)-4(3H)-quinazolinone exhibits excellent antimicrobial activity against Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. Overall, this metal-free catalytic strategy provides a straightforward, sustainable route to value-added aromatic heterocyclic chemicals, transcending the conventional petroleum-based route.