Gas-Phase Alcoholysis of Benzylic Halides in the Atmospheric Pressure Ionization Source

The present study investigates the gas-phase alcoholysis reaction of benzylic halides under atmospheric pressure chemical ionization (APCI) conditions. The APCI corona discharge is used to initiate the novel reaction, which is monitored by ion trap mass spectrometry (IT-MS). The model compound α,α,α-trifluorotoluene is applied to observe the cascade methoxylation reaction during the +APCI-MS analysis, resulting in the formation of [PhC(OCH₃)₂]⁺. Based on the results of isotopic labeling and substrate expansion experiments, an addition-elimination mechanism is proposed: initially, the reaction was initiated by the dissociation of fluorine from PhCF₃ under APCI condition, leading to the formation of [PhCF₂]⁺; subsequently, two methanol molecules nucleophilicly attack [PhCF₂]⁺ stepwisely, accompanied by the elimination of HF, yielding the product ion [PhC(OCH₃)₂]⁺. The proposed mechanism was further corroborated by theoretical calculations. The results of substrate scope expansion experiments suggest that this in-source reaction has the potential to differentiate the positional isomers of alcohols and phenols.