Are benzoylium and nitrilium ions produced from substituted 2-arene-2-oxazolines during mass spectrometry? A study based on DFT calculations, QTAIM, and ESI-MS/MS.

RATIONALE
Oxazolines are important compounds for drug development, synthesis, and pharmaceutical applications. Interest in analyzing and developing methods to characterize reaction products from these small heterocyclics has led us to study the gas-phase reactivity and fragmentation of seven 2-arene-2-oxazolines compounds by computational chemistry combined with mass spectrometry.


METHOD
Protonation sites were investigated by computed proton affinity (PA), gas-phase basicity (GB), and some quantum chemistry descriptors of reactivity; the B3LYP/6-31+G(d,p) computational model was used. Fragmentation mechanisms were suggested by employing data from collision-induced dissociation (CID), energy-resolved plots from MS/MS spectra, multiple stage experiments (MS2 ), and survival-yield method (SY).


RESULTS
Protonation studies based on Quantum Theory of Atoms in Molecules (QTAIM) and computational thermochemistry were useful to describe the reactivity of the investigated 2-arene-2-oxazolines, which can be protonated at the nitrogen atom. Three major fragmentation pathways were identified for the protonated molecules: formation of benzoylium or nitrilium ions through elimination of 71 and 72 u from the protonated molecules, respectively, and elimination of 54 u from [M+H]+ . These pathways were exploited by Density Functional Theory (DFT) calculations combined with QTAIM studies.


CONCLUSIONS
Our results can help to identify 2-arene-2-oxazoline derivatives by electrospray ionization tandem mass spectrometry (ESI-MS/MS), which can be applied for monitoring reactions through the identified diagnostic ions (product ions). Also, we can suggest that benzoylium and nitrilium ions emerge during fragmentation under CID conditions.