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:

Recent Literature

An Efficient Synthesis of 2-Aminothiophenes via the Gewald Reaction Catalyzed by an N-Methylpiperazine-Functionalized Polyacrylonitrile Fiber
L. Ma, L. Yuan, C. Xu, G. Li, M. Tao, W. Zhang, Synthesis, 2013, 45, 45-52.

Microwave-Assisted Synthesis of 5-Substituted 2-Aminothiophenes Starting from Arylacetaldehydes
G. Revelant, S. Dunand, S. Hesse, G. Kirsch, Synthesis, 2011, 2935-2940.

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

An Efficient One-Pot Synthesis of Substituted 2-Aminothiophenes via Three-Component Gewald Reaction Catalyzed by L-Proline
T. Wang, X.-G. Huang, J. Liu, B. Li, J.-J. Wu, K.-X. Chen, W.-L. Zhu, X.-Y. Xu, B.-B. Zeng, Synlett, 2010, 1351-1354.

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