Multicomponent Gewald synthesis

Another valuable multicomponent reaction is the Gewald synthesis leading to 2-acyl-3-aminothiophenes these are of current interest because they are commercially used as dyes or conducting polymers and have much pharmaceutical potential. 

Sridhar and co-workers [192] have described a microwave-promoted synthesis of 2-aminothiophenes 146 by reaction of a ketone with a nitrile and elemental sulfur using KF-alumina as a base via multicomponent condensation reaction. This method offers an efficient and convenient modification to the Gewald reaction replacing organic base with KF-alumina (Scheme 111). 

The Gewald reaction involves synthesis of 2-aminothiophenes via multicomponent condensation of a-methylene carbonyl compounds, cyano compounds, and sulfur. Recently, Tayebee et al. (2013) have successfully accomplished a rapid and efficient synthesis of 2-aminothiophenes (105) from ketones or aldehydes (103), malononi-trile (16), and sulfur (104) via a one-pot three-component Gewald reaction in the presence of a catalytic amount of ZnO nanoparticles (Scheme 9.31). The catalyst required for the reaction was synthesized through sedimentation of zinc acetate dihydrate in ethanol. 

---