Straightforward and greener synthesis of naturally occurring long chain alkylresorcinols

Abstract

Alkylresorcinols are natural phenolipids exhibiting interesting properties (e.g., antioxidant, anticancer). To monitor their bioproduction or quantify them in food samples, standards are required. However, due to their odd long alkyl chain (C > 15), only a few synthetic routes are available, with the most efficient ones relying on the Wittig reaction. To provide a more sustainable synthetic route, two major modifications were implemented: (i) the starting material was changed from 3,5-dimethoxybenzaldehyde to 3,5-dibenzyloxybenzaldehyde, thereby eliminating the need for demethylation with highly toxic reagents such as BBr₃ or HBr; and (ii) the solvent system was replaced with greener and safer alternatives - cyclopentyl methyl ether and isopropyl alcohol - instead of the toluene, dimethyl sulfoxide, and dichloromethane used in previous publications. This strategy also enabled the replacement of a four-step sequence with two one-pot two-step reactions, resulting in good overall yields of 66 % and 60 % for C:19 and C:21 alkylresorcinols, respectively.