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.

Catalytic isomerisation for synthesis of analgesic compounds.88