Effect of Fluorination on Skin Sensitization Potential and Fragrant Properties of Cinnamyl Compounds

A series of three - and three -fluorinated representatives of the family of cinnamate-derived odorants (cinnamaldehyde (1), cinnamyl alcohol (2), and ethyl cinnamate (3)) as used as fragrance ingredients is described. Olfactive evaluation shows that the fluorinated compounds exhibit a similar odor profile to their parent compounds, but the olfactive detection thresholds are clearly higher. In vitro evaluation of the skin sensitizing properties with three different assays indicates that -fluorination of Michael acceptor systems 1 and 3 slightly improves the skin sensitization profile. -Fluorocinnamyl alcohol 2b is a weaker skin sensitizer than cinnamyl alcohol 2a by invitro tests and the fluorinated product drops below the sensitization threshold of the KeratinoSens((R)) assay. On the other hand, -fluorination of compounds 1-3 results in highly reactive products which display a worsened invitro skin sensitization profile.