Fragmentation pattern of amides by EI and HRESI: study of protonation sites using DFT-3LYP data

• Published in: RSC advances Vol. 8; no. 38; pp. 2147 - 21413
• Main Authors: Fokoue, H. H, Marques, J. V, Correia, M. V, Yamaguchi, L. F, Qu, X, Aires-de-Sousa, J, Scotti, M. T, Lopes, N. P, Kato, M. J
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01.01.2018; The Royal Society of Chemistry
• Subjects: Amides; Aromatic compounds; Chemistry; Cleavage; Conjugation; Fragmentation; Molecular chains; Natural products; Nitrogen; Protonation; Spectrometry
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c7ra00408g

Amides are important natural products which occur in a few plant families. Piplartine and piperine, major amides in Piper tuberculatum and P. nigrum , respectively, have shown a typical N-CO cleavage when analyzed by EI-MS or HRESI-MS. In this study several synthetic analogs of piplartine and piperine were subjected to both types of mass spectrometric analysis in order to identify structural features influencing fragmentation. Most of the amides showed an intense signal of the protonated molecule [M + H] + when subjected to both HRESI-MS and EI-MS conditions, with a common outcome being the cleavage of the amide bond (N-CO). This results in the loss of the neutral amine or lactam and the formation of aryl acylium cations. The mechanism of N-CO bond cleavage persists in α,β-unsaturated amides because of the stability caused by extended conjugation. Computational methods determined that the protonation of the piperamides and their derivatives takes place preferentially at the amide nitrogen supporting the dominant the N-CO bond cleavage. The N-CO cleavage of α,β-unsaturated piperamides under EI and ESI is supported by computational studies.