A comprehensive study on rearrangement reactions in collision‐induced dissociation mass spectrometric fragmentation of protonated diphenyl and phenyl pyridyl ethers

Abstract

Rationale Recently, we have reported a forced degradation study of a pharmaceutical drug regorafenib which contains a phenyl pyridyl ether derivative as building block. We observed interesting rearrangements in two of its degradation products in tandem mass spectrometry (MS/MS) experiments. As diphenyl ether derivatives are also molecular building blocks of biological importance and used as herbicides and flame retardants, we decided to investigate specifically the fragmentation behavior of these compounds along with phenyl pyridyl derivatives in detail using high‐resolution electrospray ionization (ESI) MS/MS. Methods To understand the fragmentation reactions of protonated substituted diphenyl ethers and phenyl pyridyl ethers, ESI‐MS/MS experiments were performed using a quadrupole time‐of‐flight (QTOF) mass spectrometer. Results In contrast to radical cations of diphenyl ether derivatives which do not eliminate CO, the [M + H]+ ions of substituted diphenyl ethers undergo rearrangement reactions after loss of neutral molecules (H2O, HCl, etc.) to form a bicyclic structure containing a keto group and do eliminate CO. Similar rearrangement followed by fragmentation was observed for protonated phenyl pyridyl ethers and the degradation products formed from regorafenib and sorafenib. Conclusions The protonated ions of substituted diphenyl ethers and phenyl pyridyl ethers on collision‐induced dissociation have exhibited interesting rearrangement reactions, despite the nature of the substituent on both the aryl moieties. The proposed fragmentation patterns of these compounds give an insight into the understanding of gas‐phase reactions in mass spectrometric studies of diphenyl ether and phenyl pyridyl ether derivatives.

An intriguing “reversible reaction” in the fragmentation of deprotonated dicamba and benzoic acid in a Q‐orbitrap mass spectrometer: Loss and addition of carbon dioxide

“…It is worth noting that the product ions sometimes do not directly reflect the structure of the precursor ion. In the fragmentation reactions, skeleton rearrangements, 3,4 intermediate‐mediated reactions, 5,6 ion‐molecule reactions with background gases (water, nitrogen and oxygen) 7–12 and solvent (acetonitrile and methanol) addition 13,14 will lead to the formation of some unexpected product ions, which may lead to complicated MS/MS spectra and wrong structural assignments. Although such examples are not common, they are very important for structural analysis and gas‐phase ion chemistry, and have been recognized by the mass spectrometry community.…”

Topochemical Design of Cellulose-Based Carriers for Immobilization of Endoxylanase

“…This rearrangement process is caused by the interaction between the aromatic rings. 63 Here, after ionization, the molecular fragments from the diamine cellulose possibly go through a similar rearrangement eventually forming C 9 H 8 N + .…”

“…While rearrangement patterns for diphenyl ethers were elucidated earlier, , Baira and co-workers further expanded on this earlier work, demonstrating that protonated diphenyl and phenyl pyridyl ethers go through various rearrangements resulting in a multitude of ion compound peaks. This rearrangement process is caused by the interaction between the aromatic rings . Here, after ionization, the molecular fragments from the diamine cellulose possibly go through a similar rearrangement eventually forming C 9 H 8 N + .…”