It is often found in mass spectrometry that when a molecule is protonated at the thermodynamically most favorable site, no fragmentation occurs, but a major reaction is observed when the proton migrates to a different position. For benzophenones, acetophenones, and dibenzyl ether, which are all preferentially protonated at the oxygen, deacylation or dealkylation was observed in the collision-induced dissociation of the protonated molecules. For para-monosubstituted benzophenones, electron-withdrawing substituents favor the formation of RC6H4CO+ (R = substituent), whereas electron-releasing groups favor the competing reaction leading to C6H5CO+. The ln[(RC6H4CO+)/(C6H5CO+)] values are well-correlated with the sigmap+ substituent constants. In the fragmentation of protonated acetophenones, deacetylation proceeds to give an intermediate proton-bound dimeric complex of ketene and benzene. The distribution of the product ions was found to depend on the proton affinities of ketene and substituted benzenes, and the kinetic method was applied in identifying the reaction intermediate. Protonated dibenzyl ether loses formaldehyde upon dealkylation, via an ion-neutral complex of the benzyloxymethyl cation and neutral benzene. These gas-phase retro-Friedel-Crafts reactions occurred as a result of the attack of the proton at the carbon atom to which the carbonyl or the methylene group is attached on the aromatic ring, which is described as the dissociative protonation site.

The fragmentation of protonated molecules (MH(+)) in mass spectrometry usually results in even-electron product ions, but the MH(+) ions of sulfonamides are different as they often produce dominant radical cations of the constituent amines. For a series of benzenesulfonamides of anilines that bear various substituents, we found that the sulfonamides are preferentially protonated at the nitrogen, which is different from the carboxylic amides. Upon N-protonation, the S-N bond dissociates spontaneously to produce an intermediate [sulfonyl cation/aniline] complex. Within the ion-neutral complex, charge transfer between the two partners occurs in the gas phase to give rise to the ionized anilines. A substantial energy barrier was found to govern the reaction, which is consistent with the outer-sphere electron transfer mechanism. This energy barrier prevents the charge transfer when a strong electron-withdrawing substituent is attached to the aniline moiety. In contrast, when the aniline bears an electron-donating group, charge transfer is still more favorable than the dissociation of the intermediate ion-neutral complex, in spite of the existence of the energy barrier, and therefore dominates. A correlation was observed between the intensities of the ionized anilines and the ionization energies of these anilines.

In mass spectrometry of the alpha,beta-unsaturated aromatic ketones, Ph-CO-CH=CH-Ph', losses of a benzene from the two ends and elimination of a styrene are the three major fragmentation reactions of the protonated molecules. When the ketones are substituted on the right phenyl ring, the electron-donating groups are in favor of losing a styrene to form the benzoyl cation, PhCO(+), whereas the electron-withdrawing groups strongly favor loss of benzene of the left side to form a cinnamoyl cation, Ph'CH=CHCO(+). When the ketones are substituted on the left phenyl ring, the substituent effects on the reactions are reversed. In both cases, the ratios of the two competitive product ions are well-correlated with the sigma p(+) substituent constants. Theoretical calculations indicate that the carbonyl oxygen is the most favorable site for protonation, and the olefinic carbon adjacent to the carbonyl is also favorable especially when a strong electron-releasing group is present on the right phenyl ring. The energy barrier to the interconversion between the ions formed from protonation at these two sites regulates the overall reactions. Transfer of a proton from the carbonyl oxygen to the ipso position on either phenyl ring, which is dissociative, triggers loss of benzene.