Gewald Reaction

The Gewald Reaction is a synthesis of 2-aminothiophenes via a multi-component condensation between sulfur, an α-methylene carbonyl compound and an α-cyanoester.

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Mechanism of the Gewald Reaction

First step in the process is a Knoevenagel Condensation, but the remainder of the sequence is not known in detail:

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Recent Literature

Practical synthesis of tetrasubstituted thiophenes for use in compound libraries
B. P. McKibben, C. H. Cartwright, A. L. Castelhano, Tetrahedron Lett., 1999, 5471-5474.

Synthesis of Thiophene Derivatives on Soluble Polymer-Support Using Gewald Reaction
H. Zhang, G. Yang, J. Chen, Z. Chen, Synlett, 2004, 3055-3059.