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 (k•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 k•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 k•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.