Tracking Fluorine during Aqueous Photolysis and Advanced UV Treatment of Fluorinated Phenols and Pharmaceuticals Using a Combined 19 F-NMR, Chromatography, and Mass Spectrometry Approach.

Fluorine incorporation into organic molecules has increased due to desirable changes in the molecular physiochemical properties. Common fluorine motifs include: aliphatic fluorines and -CF ₃ , or -F containing groups bonded directly onto an aromatic (Ar-CF ₃ and Ar-F) or heteroaromatic ring. Photolysis of these compounds, either in natural or engineered systems, is a potential source of new fluorinated byproducts. Given the potential persistence and toxicity of fluorinated byproducts, monitoring of product formation during photolysis of various fluorinated motifs is needed. ¹⁹ F-NMR is a means to detect and quantify these species. Ar-CF ₃ and Ar-F model compounds (2-, 3-, and 4-(trifluoromethyl)phenol, 2-, 3-, 4-fluorophenol, and 2,6-, 3,5-difluorophenol) were photolyzed under a variety of aqueous conditions: pH 5, pH 7, pH 10, 1 mM H ₂ O ₂ at pH 7 to form •OH, and 0.5 mM SO ₃ ^2- at pH 10 to form e _aq ^- . Pharmaceuticals with the Ar-CF ₃ (fluoxetine) and Ar-F plus pyrazole-CF ₃ (sitagliptin) motifs were treated similarly. Parent molecule concentrations were monitored with high pressure liquid chromatography with a UV detector. Fluorine in the parent and product molecules was quantified with ¹⁹ F-NMR and complete fluorine mass balances were obtained. High resolution mass spectrometry was used to further explore product identities. The major product for Ar-F compounds was fluoride. The Ar-CF ₃ model compounds led to fluoride and organofluorine products dependent on motif placement and reaction conditions. Trifluoroacetic acid was a product of 4-(trifluoromethyl)phenol and fluoxetine. Additional detected fluoxetine products identified using mass spectrometry resulted from addition of -OH to the aromatic ring, but a dealkylation product could not be distinguished from fluoxetine by ¹⁹ F-NMR. Sitagliptin formed multiple products that all retained the pyrazole-CF ₃ motif while the Ar-F motif produced fluoride. ¹⁹ F-NMR, mass spectrometry, and chromatography methods provide complementary information on the formation of fluorinated molecules by modification or fragmentation of the parent structure during photolysis, allowing screening for fluorinated photoproducts and development of fluorine mass balances.
Competing Interests: The authors declare no competing financial interest.
(© 2022 The Authors. Published by American Chemical Society.)