Spontaneous aqueous defluorination of trifluoromethylphenols: substituent effects and revisiting the mechanism

Abstract

Trifluoromethylphenols (TFMPs) are environmental contaminants that exist as transformation products of aryl-CF₃ pharmaceuticals and agrochemicals. Their –CF₃ moiety raises concerns as it may form problematic fluorinated transformation products such as the persistent pollutant trifluoroacetic acid (TFA). This study investigates the hydrolysis and spontaneous defluorination mechanisms of 2-TFMP, 3-TFMP, 4-TFMP, and 2-Cl-4-TFMP under environmentally relevant aqueous conditions, and under alkaline pH to investigate the mechanism of defluorination. 3-TFMP did not undergo hydrolysis. The other TFMPs reacted to primarily form the corresponding hydroxybenzoic acids and fluoride. High-resolution mass spectrometry identified a benzoyl fluoride intermediate in the hydrolysis of 4-TFMP and other dimer-like transformation products of the 4- and 2-Cl-4-TFMP. Density functional theory calculations revealed that the key defluorination step likely proceeds via an E1cb mechanism, driven by β-elimination. Experimental and computational results demonstrated substituent-dependent differences in reactivity, and the importance of the deprotonation of TFMPs for the hydrolysis reaction to proceed. These findings provide mechanistic insights into the complete defluorination of TFMPs and broader implications for the environmental defluorination of other PFAS.