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Updated: Jun 22, 2026

Characterizing Lewis Pairs Using Titration Coupled with In Situ Infrared Spectroscopy
Published on: February 20, 2020
Brønsted acidity of substrates influences the outcome of passerini three-component reactions
Babajide O Okandeji1, Jason K Sello
1Department of Chemistry, Brown University, 324 Brook Street, Providence, Rhode Island 02912, USA.
Abstract:
Passerini three-component reactions of aldehydes, isocyanides, and strong carboxylic acids (i.e., pK(a) < 2) yield alpha-acyloxycarboxamides and/or alpha-acylaminocarboxamides, the characteristic products of Ugi four-component reactions. We propose that alpha-acylaminocarboxamide formation with these substrates is a consequence of in situ Brønsted acid-catalyzed reaction of the isocyanide and aldehyde to yield an imine that participates in an Ugi-type reaction. The apparent transfer of the isocyanide alpha-carbon to protic solvents as a formyl group during imine formation is indicative of new isocyanide reactivity.
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A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions

