Cyanoacetamide MCR (III): three-component Gewald reactions revisited
Kan Wang1, Dabin Kim, Alexander Dömling
1University of Pittsburgh, Drug Discovery Institute, Pittsburgh, PA 15261, USA.
Abstract:
Cyanoacetic acid derivatives are the starting materials for a plethora of multicomponent reaction (MCR) scaffolds. Here we describe valuable general protocols for the synthesis of arrays of 2-aminothiophene-3-carboxamides from cyanoacetamides, aldehydes or ketones, and sulfur via a Gewald-3CR variation. In many cases the reactions involve a very convenient work up by simple precipitation in water and filtration. More than 40 new products are described. We foresee our protocol and the resulting derivatives to become very valuable to greatly expanding the MCR scaffold space of cyanoacetamide derivatives.
Related Concept Videos
Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview
Acid Halides to Amides: Aminolysis
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
Reactions of Acid Anhydrides
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
Alkenes via Reductive Coupling of Aldehydes or Ketones: McMurry Reaction


