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