Fragmentation of Protonated Amides Through Intermediate Ion–Neutral Complexes: Neighboring Group Participation

Abstract

It has been shown that neighboring group participation plays an important role in the fragmentation of protonated amides; the attachment of an adjacent functional group capable of accepting a proton provides alternative pathways of low energy for the formation of the inevitable N-protonated species in the fragmentation of the amide bond. Under methane chemical ionization (CI) conditions, protonated aniline ( m/ z 94) is only 1.6% of the base peak MH + ion for acetanilide; the abundance of the m/ z 94 ion is increased to 15% for acetoacetanilide and protonated o-methoxyaniline reaches a relative intensity of 49% for N-acetyl- o-methoxyaniline. A more striking difference in ease of the formation of protonated anilines is found for acetanilides bearing a nitro group at different positions. Protonated nitroaniline ( m/ z 139) is the base peak in the methane CI spectrum of N-acetyl- o-nitroaniline; the m/ z 139 ion drops to only 0.7% for the para isomer, and this ion is increased to 31.5% in the spectrum of N-acetoaceto- p-nitroaniline. By employing low energy collision-induced dissociation, it has been found that the fragmentation of protonated amides proceeds by way of ion–neutral complexes. In the case of acetanilide, for example, the cleavage of the amide bond gives rise to an acetylium ion and neutral aniline, which are bound together as a complex. An α-hydrogen of the acetylium ion, which is activated by the positive charge, is captured by aniline due to its higher proton affinity as compared with ketene. For those compounds having mobile protons other than the amidic hydrogen, it is indicated that such proton has the priority to be transferred in the reaction. Thus, the proton on the free carboxyl group of N-phenyl succinic and maleic monoamides is transferred in the fragmentation, leading to anhydrides as the neutral species in the formation of protonated aniline.