An unprecedented rearrangement in collision‐induced mass spectrometric fragmentation of protonated benzylamines

Abstract

The collision-induced dissociation (CID) mass spectra of several protonated benzylamines are described and mechanistically rationalized. Under collision-induced decomposition conditions, protonated dibenzylamine, for example, loses ammonia, thereby forming an ion of m/z 181. Deuterium labeling experiments confirmed that the additional proton transferred to the nitrogen atom during this loss of ammonia comes from the ortho positions of the phenyl rings and not from the benzylic methylene groups. A mechanism based on an initial elongation of a C--N bond at the charge center that eventually cleaves the C--N bond to form an ion/neutral complex of benzyl cation and benzylamine is proposed to rationalize the results. The complex then proceeds to dissociate in several different ways: (1) a direct dissociation to yield a benzyl cation observed at m/z 91; (2) an electrophilic attack by the benzyl cation within the complex on the phenyl ring of the benzylamine to remove a pair of electrons from the aromatic sextet to form an arenium ion, which either donates a ring proton (or deuteron when present) to the amino group forming a protonated amine, which undergoes a charge-driven heterolytic cleavage to eliminate ammonia (or benzylamine) forming a benzylbenzyl cation observed at m/z 181, or undergoes a charge-driven heterolytic cleavage to eliminate diphenylmethane and an immonium ion; and (3) a hydride abstraction from a methylene group of the neutral benzylamine to the benzylic cation to eliminate toluene and form a substituted immonium ion. Corresponding benzylamine and dibenzylamine losses observed in the spectra of protonated tribenzylamine and tetrabenzyl ammonium ion, respectively, indicate that the postulated mechanism can be widely applied. The postulated mechanisms enabled proper prediction of mass spectral fragments expected from protonated butenafine, an antifungal drug.

Gas-Phase Chemistry of Benzyl Cations in Dissociation ofN-Benzylammonium andN-Benzyliminium Ions Studied by Mass Spectrometry

“…The attack at the phenyl ring has been reported in previous studies [20][21][22]. A new case that INC-mediated electrophilic aromatic substitution reaction between benzyl cation and imidazole derivatives was observed during the fragmentation of N,N'-dibenzylimidazolium cations ( Table 2).…”

“…In other pathways, the benzyl cation can attack the phenyl ring via INC-7 resulting in the formation of product ions including m/z 185, m/z 181, and m/z 95, which depends on the shift of the replaced proton. It is noteworthy that electrophilic substitution by the benzyl cation can occur at different positions of the aromatic ring, so product ions at m/z 185 and 181 are probably mixtures of several isomers, which has been investigated and demonstrated in the studies of other multibenzyl-substituted compounds [20][21][22]. In this study, the isomerized product ions are no longer discussed in detail.…”

“…In electrospray ionization mass spectrometry (ESI-MS), fragmentation of benzylated cations prefers to generate benzyl cations [7,8,[20][21][22][23][24][25][26][27][28][29][30], though a few exceptions have been reported that tropylium ion can be co-produced in the fragmentation of benzylpyridinium ions [18,31,32]. Besides the formation of benzyl cations, other interesting ions resulting from hydride transfer [24,25] or electrophilic aromatic substitution reactions [20][21][22] via the nonconventional ion/neutral complex (INC) can also be generated in the dissociation of benzylated cations.…”

“…Consequently, a need for other examples of INC-mediated reactions is evident in order to better understand the fragmentation reactions in the contemporary ESI mass spectrometry, a method that has become one of the most popular analytical methods. Thus, renewed interest in studies on INC-mediated fragmentation reactions has emerged in recent years [8,[20][21][22][23][24][25][39][40][41][42][43][44][45][46][47].…”

Decarboxylative Coupling Reaction in ESI(−)-MS/MS of 4-Nitrobenzyl 4-Hydroxybenzoates: Triplet Ion–Neutral Complex-Mediated 4-Nitrobenzyl Transfer

“…However, the gasphase C-C coupling reactions such as methyl and benzyl transfers that occur in tandem mass spectrometry (MS/MS) often cause problems in MS-based structural elucidations, and have therefore attracted much attention [4][5][6][7]. Benzyl cations are relatively stable in the gas phase and are easily formed during MS by fragmentation of benzylated species [8,9].…”