Gas-phase Smiles rearrangement reactions of deprotonated N-phenylbenzamides studied by electrospray ionization tandem mass spectrometry

RATIONALE: Electrospray ionization tandem mass spectrometry (ESI-MSn) is an invaluable tool for the study of gas-phase reactions. When N-phenylbenzamide is analyzed in negative ion mode, the nucleophilic deprotonated site of nitrogen or oxygen, together with the adjacent electrophilic phenyl carbon in the same molecule, provides a useful opportunity to study the intramolecular nucleophilic reaction in the gas phase. METHODS: AllMS(n) experiments of deprotonated N-phenylbenzamides were conducted on an ion trap mass spectrometer using ESI in negative ionmode. The accuratemasses of fragments were measured on an ESI quadrupole time-of-flight mass spectrometer in negative ion mode. Theoretical calculations were conducted at the B3LYP/6-31++ G(d, p) level of density functional theory using the Gaussian 03 program. RESULTS: When the polarity of the substituent on the aniline ring was changed, gas-phase Smiles rearrangement reactions could be initiated by different atoms in the anionic center. Upon collisional activation, loss of CO from deprotonated N-phenylbenzamides could be observed, which can be interpreted as a nitrogen anion triggering the Smiles rearrangement reaction through a three-membered ring transition state. As the aniline ring was substituted by a strong electron-withdrawing group (e. g., NO2, COCH3, or CF3) at the para position, a characteristic phenolate anion was obtained, which was derived from the Smiles rearrangement reaction initiated by the oxygen anion through a four-membered ring transition state. CONCLUSIONS: In the fragmentation of deprotonated N-phenylbenzamides, the gas-phase Smiles rearrangement reaction initiated by either the nitrogen or the oxygen atom can proceed. The findings in this study have not only enriched knowledge on the gas-phase Smiles rearrangement reactions, but also provided valuable information for understanding the rearrangements of deprotonated aromatic amides in gas phase. Copyright (C) 2015 John Wiley & Sons, Ltd.