Tracking Fluorine during Aqueous Photolysis and Advanced UV Treatment of Fluorinated Phenols and Pharmaceuticals Using a Combined 19F-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 - CF3, or -F containing groups bonded directly onto an aromatic (Ar-CF3 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. 19F-NMR is a means to detect and quantify these species. Ar-CF3 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 H2O2 at pH 7 to form (OH)-O-circle, and 0.5 mM SO32- at pH 10 to form e(aq)(-). Pharmaceuticals with the Ar-CF3 (fluoxetine) and Ar-F plus pyrazole-CF3 (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 19F-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-CF3 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 F-19-NMR. Sitagliptin formed multiple products that all retained the pyrazole-CF3 motif while the Ar-F motif produced fluoride. F-19-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.

Automated summary

Fluorine incorporation into organic molecules has increased due to desirable changes in the molecular physiochemical properties. Photolysis of fluorinated compounds can lead to the formation of new fluorinated byproducts. Monitoring of product formation during photolysis of various fluorinated motifs is important due to the potential persistence and toxicity of these byproducts. 19F-NMR is a useful method to detect and quantify fluorine-containing species.