The mechanism of the Ugi four-component reaction has been investigated by electrospray ionization (tandem) mass spectrometry using charge-tagged reagents (a carboxylic acid or an amine) to favour detection. Key intermediates were transferred directly via ESI(+) from the reaction solution to the gas phase and characterized by MS measurements and MS/MS collision induced dissociation. The Mumm rearrangement (final step) was also investigated by both travelling wave ion mobility mass spectrometry and DFT calculations. The data seem to consolidate the amazingly selective mechanism of this intricate four-component reaction.
The current manuscript describes the role and importance of catalysis and solvent effects for the Biginelli multicomponent reaction. The overwhelming number of new catalysts and conditions recently published for the Biginelli synthesis, including in some manuscripts entitled "catalyst-free" and/or "solvent-free" have incentivized controversies and hot debates regarding the importance of developing new catalysts and reaction conditions to perform this very important multicomponent reaction. These so-called "catalyst-free" reports have generated much confusion in the field, requiring urgent elucidations. In this manuscript, we exemplify, demystify, and discuss the crucial role of catalysis, solvent effects, mechanisms, kinetics, facts, presumptions, and myths associated with the Biginelli reaction aiming to avoid current and future confusion and to stimulate new approaches.
The use of a charge-tagged acrylate derivative bearing an imidazolium tag to study the Morita-Baylis-Hillman reaction via ESI-MS(/MS) monitoring and the effect of such tag (imidazolium cations and ion pairs) over TSs is described. The ionic nature of the substrate was meant to facilitate ESI transfer to the gas phase for direct mass spectrometric analysis. The detection and characterization of charged intermediates has suggested major reaction pathways. DFT calculations considering the effect of a polar and protic solvent (methanol), of a polar and aprotic solvent (acetonitrile), and of no solvent (gas phase) were used to predict possible TSs through a common accepted intermediate. The controversial proton transfer step, which may proceed via Aggarwal's or McQuade's proposals, was evaluated. Calculations predicted the formation of electrostatic intermediate complexes with both the cation and anion when charge-tagged reagents are used. These complexes contribute to the positive ionic liquid effect, and based on the formation of these unique complexes, a rationale for the ionic liquid effect is proposed. These complexes also pointed to a plausible explanation for the positive ionic liquid effect observed in several reactions that are difficult to be carried out in organic solvents but have shown a beneficial effect when performed in ionic liquids.
The current article
describes the synthesis, characterization,
and application of a designed hybrid fluorescent BTD–coumarin
(2,1,3-benzothiadiazole-coumarin) derivative (named BTD-Lip). The use of BTD-Lip for live-cells staining showed
excellent results, and lipid droplets (LDs) could be selectively stained.
When compared with the commercially available dye (BODIPY) for LD
staining, it was noted that the designed hybrid fluorescence was capable
of staining a considerable larger number of LDs in both live and fixed
cells (ca. 40% more). The new dye was also tested on live Caenorhabditis elegans (complex model) and showed
an impressive selectivity inside the worm, whereas the commercial
dye showed no selectivity in the complex model.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.