Photochemical Formation of Trifluoroacetic Acid: Mechanistic Insights into a Fluoxetine-Related Aryl-CF3 Compound

Abstract

Trifluoroacetic acid (TFA) is a ubiquitous environmental contaminant; however, its sources are poorly constrained. One understudied source is from the photochemical reactions of aromatic compounds containing −CF₃ moieties (aryl-CF₃) including many pharmaceuticals and agrochemicals. Here, we studied the aqueous photochemistry of 4-(trifluoromethyl)phenol (4-TFMP), a known transformation product of the pharmaceutical fluoxetine. When exposed to lamps centered at UV-B, 4-TFMP formed up to 9.2% TFA at a steady state under acidic conditions and 1.3% under alkaline conditions. TFA yields of fluoxetine were similar to 4-TFMP for acidic and neutral pH, but higher at alkaline pH, suggesting that fluoxetine may have a mechanism of TFA formation in addition to via the 4-TFMP intermediate. Use of an ¹³CF₃ isotopologue of 4-TFMP allowed for the tracking of TFA formation, which formed via multiple oxidative additions prior to oxidative ring cleavage. The oxidation is mediated by reactive oxygen species (ROS) generated through self-sensitized photolysis, with singlet oxygen and hydroxyl radicals as the key ROS. In addition to the TFA formation mechanism, other photochemical reactions of 4-TFMP resulted in defluorination and dimerization. Overall, this work expands our understanding of how TFA forms from aryl-CF₃ compounds to better understand the total global burden of TFA.