Hydride transfer reactions via ion–neutral complex: fragmentation of protonated N‐benzylpiperidines and protonated N‐benzylpiperazines in mass spectrometry

Abstract

An ion-neutral complex (INC)-mediated hydride transfer reaction was observed in the fragmentation of protonated N-benzylpiperidines and protonated N-benzylpiperazines in electrospray ionization mass spectrometry. Upon protonation at the nitrogen atom, these compounds initially dissociated to an INC consisting of [RC(6)H(4)CH(2)](+) (R = substituent) and piperidine or piperazine. Although this INC was unstable, it did exist and was supported by both experiments and density functional theory (DFT) calculations. In the subsequent fragmentation, hydride transfer from the neutral partner to the cation species competed with the direct separation. The distribution of the two corresponding product ions was found to depend on the stabilization energy of this INC, and it was also approved by the study of substituent effects. For monosubstituted N-benzylpiperidines, strong electron-donating substituents favored the formation of [RC(6)H(4)CH(2)](+), whereas strong electron-withdrawing substituents favored the competing hydride transfer reaction leading to a loss of toluene. The logarithmic values of the abundance ratios of the two ions were well correlated with the nature of the substituents, or rather, the stabilization energy of this INC.

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

“…The ionic and neutral components of an INC show reactivities similar to those expected for the isolated species in the bimolecular reactions. In previous studies, we found dissociation of protonated N-benzyl amines gave rise to [benzyl cation/amine] complex and then nucleophilic aromatic substitution [8], electron transfer [23], or hydride transfer [24] could occur within the complex in different cases. In the present study, we systematically investigated the gas-phase reactions of benzyl cations with neutral N-containing species through INC intermediates in collision-induced dissociation of N-benzylated cations in ESI-MS. With these efforts, we try to figure out a more integrated landscape of the gas-phase reactivity of benzyl cations.…”

“…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

“…The sum of the free energy of the separated 2-methoxy-4-carboxylate-phenoxyl and nitrobenzyl radicals is higher than that of 1-INC-t by 24.7 kJ/mol; this indicates that 1-INC-t is relatively stable. INC is an important intermediate in gasphase chemistry, and various chemical reactions can occur between the two species or in the ionic fragment alone prior to its final separation [6,8,17,[19][20][21][22][23][24]. In addition to direct separation to Figure 5S).…”

Anomerization of Acrylated Glucose During Traveling Wave Ion Mobility Spectrometry

“…Accordingly, a mechanism allowing consecutive elimination of ammonia and water could be proposed in the case of α-Glu-5A. As depicted in Scheme 2a with dashed arrows, an anchimerically-assisted process [37][38][39][40][41], occurring here via a nucleophilic attack of one oxygen atom from the acrylate moiety in C1 onto the carbonyl carbon of the acrylate group in C2 would allow elimination of NH 3 from the precursor ion to produce a stable m/z 451.1 fragment. The newly created OH group in this product ion would further be eliminated as a water molecule upon a 1,6-proton transfer, yielding the m/z 433.1 product ion.…”