AbstractCompetingorthointeractions, involving the CX and theortho‐methyl substituent on the 3‐phenyl moiety, resulting in the eliminations of˙CH3and˙OH/˙SH from the molecular ions of 2‐substituted‐3‐(2‐methylphenyl)‐4(3H)‐quinazolinones and their thio analogues, were observed. An intramolecular aromatic substitution of the heteroatom of CX at theortho‐carbon of the 3‐phenyl moiety ejecting the methyl group and a hydrogen transfer from the same ortho‐methyl substituent to the heteroatom of CX resulting in the expulsion of˙XH are envisaged for the dualorthointeraction. Another expected fragmentation process observed in these compounds is the transfer of the aryl group from the 3‐position of the heterocycle to the heteroatom of CX leading to the elimination of ArX˙from the molecular ions. The proposed fragmentation processes and the ion structures are supported by high‐resolution data,B/EandB2/Elinked‐scan spectra, collisionally activated decompositionB/Espectra and deuterium isotopic labelling.