Solid-catalyzed synthesis of isomers–free terpinen–4–ol

Abstract

Terpinen–4–ol is a natural product with wide application in the fragrance and agrochemical industry, currently extracted from tea tree oil or synthesized from either base–promoted rearrangement of 1,4–cineol or acid–catalyzed hydration of limonene. However, these synthetic processes, based on aggressive, unrecoverable homogeneous reagents, are non–selective and give significant amounts of isomers, which severely complicate and make more expensive the purification of the active substance. Here we show the isomers–free synthesis of terpinen–4–ol, exclusively over solid catalysts such as alumina, nanotitania and Pd/C, in >60% yield, by selective epoxidation, isomerization of terpinolene epoxide and allyl alcohol hydrogenation. The synthesis can be performed either in batch or in flow mode for the isomerization of terpinolene epoxide. The use of bare nanotitania as a selective epoxide isomerization catalyst, here demonstrated, opens new ways for the synthesis of quaternary alcohols.