A fixed‐charge model of the N‐protomer of 4‐aminobenzoic acid to facilitate the study of the unimolecular and bimolecular chemistry of its “neutral” carboxylic acid group

Abstract

RationaleThere are a growing number of examples of protomers formed via electrospray ionization (ESI) that do not fragment under mobile proton conditions, giving rise to distinct tandem mass spectra. To model the N‐protomer of 4‐aminobenzoic acid, here we study the gas‐phase unimolecular and bimolecular chemistry of the 4‐(carboxyphenyl)trimethylammonium ion.Methods4‐(Carboxyphenyl)trimethylammonium iodide was synthesized, purified via recrystallization and transferred to the gas phase via ESI. 4‐(Carboxyphenyl)trimethylammonium ion, 7, was mass selected and subjected to collision‐induced dissociation and ion–molecule reactions in a linear ion trap mass spectrometer.ResultsThe major fragmentation channel for the fixed‐charge cation 7 is methyl radical loss, whereas loss of trimethylamine and CO2 represents minor pathways. The free carboxylic acid functional group of 7 is unreactive toward a number of neutral reagents (methanol, acetone, acetonitrile, and N,N′‐diisopropylcarbodiimide). 7 reacts very slowly with trimethylborate via addition‐elimination, consistent with density functional theory (DFT) calculations that show this reaction is slightly endothermic. The deuterated cation 7(D) undergoes slow D/H exchange with ethanol, and DFT calculations reveal that a flip‐flop mechanism operates.ConclusionsThe free carboxylic group of 7 is not very reactive toward neutral reagents in the gas phase.