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

A series of three α- and three β-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 α-fluorination of Michael acceptor systems 1 and 3 slightly improves the skin sensitization profile. α-Fluorocinnamyl alcohol 2b is a weaker skin sensitizer than cinnamyl alcohol 2a by in vitro tests and the fluorinated product drops below the sensitization threshold of the KeratinoSens assay. On the other hand, β-fluorination of compounds 1 - 3 results in highly reactive products which display a worsened in vitro skin sensitization profile.