Two-step synthesis of monoterpenoid dioxinols exhibiting analgesic activity from isopulegol and benzaldehyde over heterogeneous catalysts

•Two-step synthesis of dioxinol from isopulegol and benzaldehyde.•Isomerization of tetrahydropyran produced in the first step over ceria composite.•Mildly acidic and basic catalysts active and selective for isomerization.•Formation of tetrahydropyran dehydration product over ion exchange resin.•Reaction of tetrahydropyran to dioxinol by dehydration-hydration and ring closure.

Benzodioxinols, compounds with 6-membered heterocycles containing two oxygen atoms, exhibit promising analgesic activity. In the current study, synthesis of dioxinol via two-step approach including Prins cyclization of isopulegol with benzaldehyde to tetrahydropyran and its ring-rearrangement to dioxinol was investigated. Different acidic and basic catalysts were studied in the second step and the highest selectivity toward dioxinol was achieved using mesoporous Ce-composite material.

Graphical abstractCatalytic isomerisation for synthesis of analgesic compounds.Download high-res image (88KB)Download full-size image