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.