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Collision‐induced dissociation of phenethylamides: role of ion‐neutral complexes
Author(s) -
Nikolić Dejan,
Macias Carmen,
Lankin David C.,
Breemen Richard B.
Publication year - 2017
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.7915
Subject(s) - chemistry , fragmentation (computing) , dissociation (chemistry) , molecule , mass spectrometry , electrospray ionization , tandem mass spectrometry , collision induced dissociation , ion , computational chemistry , electrospray , organic chemistry , chromatography , computer science , operating system
Rationale Phenethylamides are a large group of naturally occurring molecules found both in the plant and animal kingdoms. In addition, they are used as intermediates for the synthesis of pharmaceutically important dihydro‐ and tetrahydroisoquinolines. To enable efficient characterization of this class of molecules, a detailed mass spectrometric fragmentation study of a broad series of analogs was carried out. Methods The test compounds were synthesized using standard methods for amide bond formation. Low‐energy high‐resolution tandem mass spectra were acquired on a hybrid quadrupole/time‐of‐flight mass spectrometer using positive ion electrospray ionization. Results A total of 26 analogs were investigated in the study. Fragmentation of phenethylamides was found to proceed via intermediate ion‐neutral complexes. The complexes can break down via multiple pathways including dissociation, proton transfer, Friedel‐Crafts acylation, and single electron transfer. The relative contribution of each of these pathways strongly depends on the structure of the coupling amine and acid. Conclusions A general scheme for the fragmentation of phenethylamides was developed. This study further extends the knowledge base of the ion‐neutral complex by discovering Friedel‐Crafts acylation as a novel reaction. The strong influence of minor structural modifications on the fragmentation patterns highlights the importance of testing many analogs in order to fully predict a fragmentation pattern of a particular class of molecules.