The Chemistry of Drugs. VI. Thermal Decomposition of Qinghaosu

Hearing qinghaosu in refluxing rylene for 22 h afforded decomposition products 2 and 4 in 15% yield each.Structures of Z and 4 were assigned based on their In-NMR and I3c-NM~ data and the former confirmed by a single crystal X-ray analysis.Structure 4, supported by spectral data and a successful 0-acetylation of the OH group remains tentative.Structures 2 and 4 contain a newly formed tetrahydrofuran ring, originating by breakage of the 0rigiw.1 ~eraxids group.Thermal decomposition of the antimalarial sesquirerpene qinghaosu (1, QHS), was hoped to afford products which could be connected with intermediates of its total synthesis. 2If was expected that such studies would in addition provide valuable first hand information on the thermal stability of the peroxide group in QHS and the course of its fragmentation.we now would like to report our findings made by heating QHS in refluxing xylene for 22 h.In contrast ro hearing 1 in toluene which afforded practically no decomposition products, or tetralin, which afforded too many decomposition praducrs, hearing 1 in xylene under reflun afforded and 5 in 15% each, 1 isolated by chromatography on silica gel.Mass spectrometrp (mass 282) and H-NMR and 13c-NM~ data (22 protons and 15 carbons)