Identification of Aliphatic and Aromatic Tertiary N-Oxide Functionalities in Protonated Analytes via Ion/Molecule and Dissociation Reactions in an FT-ICR Mass Spectrometer

Abstract

A mass spectrometric method is presented for the identification of compounds that contain the aliphatic or aromatic N-oxide functional group. This method utilizes gas-phase ion/molecule reactions of tri(dimethylamino)borane (TDMAB), which rapidly derivatizes protonated aliphatic and aromatic tertiary N-oxides, amides, and some amines via loss of dimethylamine in a Fourier transform ion cyclotron resonance mass spectrometer. The mechanism involves proton transfer from the protonated analyte to the borane, followed by addition of the analyte to the boron center and elimination of dimethylamine. The derivatized analytes are readily identified on the basis of their m/z value which is 98 Th (thomson) greater than that of the protonated analyte, and the characteristic boron isotope patterns. SORI-CAD of the product ions (adduct-(CH3)2NH) yields different fragment ions for aliphatic tertiary N-oxides, aromatic tertiary N-oxides, amides, and pyridines. Therefore, these analytes can be identified based on their characteristic fragment ions. This method was tested by examining two drug samples, Olanzapine and Olanzapine-4' N-oxide.

Mass spectrometric identification of the N‐monosubstituted N‐hydroxylamino functionality in protonated analytes via ion/molecule reactions in tandem mass spectrometry

“…[17,18,20] MOP was found to form an abundant stable adduct with protonated N-oxides, sulfoxides and diamines (all with PA~220 kcal/mol), which is useful for their identification. [17,18,20] Moreover, adduct-MeOH was the only major product observed when MOP was allowed to react with protonated o-phenylenediamine but not for m-phenylenediamine and p-phenylenediamine. Scheme 1 shows a proposed mechanism that involves proton transfer followed by two nucleophilic attacks by the amino functionalities to the quaternary carbon center of MOP, which leads to the loss of a methanol molecule.…”

“…MS/MS methods based on ion/molecule reactions of ionized analytes hold great promise for being able to provide information useful in the identification of specific functional groups . Our group has successfully developed such methods for the identification of many different functionalities in protonated analytes . In the work presented here, gas‐phase ion/molecule reactions of 2‐methoxypropene (MOP) are demonstrated to allow the identification of the protonated N ‐monosubstituted hydroxylamine functionality in a liner quadrupole ion trap.…”

“…[11][12][13][14][15] Our group has successfully developed such methods for the identification of many different functionalities in protonated analytes. [12][13][14][15][16][17][18][19][20] In the work presented here, gas-phase ion/molecule reactions of 2-methoxypropene (MOP) are demonstrated to allow the identification of the protonated N-monosubstituted hydroxylamine functionality in a liner quadrupole ion trap.…”

Identification of 2-Aminothiazolobenzazepine Metabolites in Human, Rat, Dog, and Monkey Microsomes by Ion-Molecule Reactions in Linear Quadrupole Ion Trap Mass Spectrometry

“…(Brodbelt, 1997;Watkins et al, 2004Watkins et al, , 2005Eberlin, 2006;Fu et al, 2012;Osburn and Ryzhov, 2013). Several neutral reagents for GPIMR such as dimethyl disulfide (DMDS), tert-butyl peroxide (TBP), and tri (dimethylamino)borane (TDMAB) have been developed to identify oxidized heteroatom functionalities (Watkins et al, 2005;Duan et al, 2008Duan et al, , 2009Fu et al, 2012). These GPIMR reagents react with functional groups of the protonated analyte molecules in the ion trap and generate unique products that can be further fragmented by collisioninduced dissociation (CID) to generate characteristic product ions or neutral molecules specific to the functional groups.…”

Total Synthesis of Maoecrystal V

“…In our final attempt to achieve the total synthesis of maoecrystal V( 1 ), we explored the possibility of using as tepwise strategyf or the formation of product 41.I tw as envisaged that the C1 position couldbebrominated using an N-bromosuccinimide (NBS)-mediated radicalr eaction, and that the resulting bromide could be converted into the corresponding ketone using a4 -methoxypyridine-N-oxide-mediated S N 2r eaction. [27] In practice, compound 13 was initially treated with SmI 2 to remove its acetyl group, and subsequently brominated with NBS in the presence of benzoyl peroxide. [28] Unfortunately,h owever,t hese reactionconditions led to the formation of the dibrominatedp roduct 43.T oa void bromination at C16, 13 wasu sed as the substrate in the bromination reaction, where it was treated with NBS in the presence of benzoyl peroxide to give the mono-brominated 44 in 90 %y ield.…”