The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

• Published in: Chemistry : a European journal Vol. 15; no. 38; pp. 9799 - 9804
• Main Authors: De Souza, Rodrigo O. M. A., da Penha, Eduardo T. , Milagre, Humberto M. S., Garden, Simon J., Esteves, Pierre M., Eberlin, Marcos N., Antunes, Octavio A. C.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 28.09.2009
• Subjects: Biginelli reaction; Cations - chemistry; density functional calculations; electrospray mass spectrometry; heterocyclic compounds; Heterocyclic Compounds - chemistry; reaction mechanisms; Spectrometry, Mass, Electrospray Ionization
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200900470

Biginelli reactions have been monitored by direct infusion electrospray ionization mass spectrometry (ESI‐MS) and key cationic intermediates involved in this three‐component reaction have been intercepted and further characterized by tandem MS experiments (ESI‐MS/MS). Density functional theory calculations were also used to investigate the feasibility of the major competing mechanisms proposed for the Biginelli reaction. The experimental and theoretical results were found to corroborate the iminium mechanism proposed by Folkers and Johnson, whereas no intermediates directly associated with either the more energy demanding Knoevenagel or enamine mechanisms could be intercepted. Key cationic intermediates involved in the three‐component Biginelli reaction (see scheme) have been intercepted and further characterized by tandem MS experiments (ESI‐MS/MS). The experimental and theoretical results were found to corroborate the iminium mechanism proposed by Folkers and Johnson, whereas no intermediates directly associated with either the more energy demanding Knoevenagel or enamine mechanisms could be intercepted.