Stranger Rings: How Heteroarenes and the Degree of Methyl Group Fluorination Affect Photolysis Kinetics and Fluorinated Product Formation

Pharmaceuticals and pesticides containing a variety of fluorinated aromatic structures undergo direct and indirect photolysis, producing fluorinated products. An assessment of how structural factors, including the ring structure and degree of fluorination, influence photolysis rates and the formation of fluorinated products is needed to understand the overall persistence and impacts of these fluorinated compounds. The direct photolysis and reaction with hydroxyl radicals of model trifluoromethyl-substituted compounds with benzene, pyridine, pyrazine, pyrimidine, imidazole, pyrazole, and triazole rings were investigated to determine quantum yields and second-order rate constants (<i>k</i>_•OH). Experiments with a suite of substituted benzoic acids and pyridines were also performed to evaluate the reactivity and extent of defluorination of mono-, di-, and trifluoromethyl groups. Intermediate and final degradation products were analyzed using fluorine nuclear magnetic resonance (¹⁹F NMR) spectroscopy and mass spectrometry. Increasing the number of nitrogen atoms in the aromatic ring decreases both direct and indirect photolysis rates by lowering quantum yields (up to 10-fold) and <i>k</i>_•OH values (up to 100-fold). In contrast, decreasing the degree of fluorination on the methyl group increases quantum yields by up 100-fold and <i>k</i>_•OH by increments of ∼1 × 10⁹ M^-1 s^-1 per additional H atom. Moreover, the presence of ring nitrogen atoms inhibits defluorination processes more than it inhibits processes leading to the formation of fluoroacetic acid and fluoroacetamide byproducts. These insights enhance our understanding of photodegradation mechanisms in fluoromethyl (hetero)aromatic compounds and structural factors critical for evaluating and limiting the formation of fluorinated byproducts.