Several compounds that contain the 2-aminothiophene structural motif have been found to be promising pharmacological
agents, such as the antipsychotic drug olanzapine, which has already been commercialised. There are many approaches to the synthesis of
2-aminothiophenes; however, the Gewald reaction is considered to be the simplest and most convergent method for generating these heterocycles.
The reaction is reviewed from its original development to the most recent advances in terms of substrate scope, reactivity, reaction
conditions, and synthetic applications.