Hp. Buchstaller et al., Synthesis of novel 2-aminothiophene-3-carboxylates by variations of the Gewald reaction, MONATS CHEM, 132(2), 2001, pp. 279-293
The synthesis of the title compounds through variations of the Gewald react
ion is presented. Knoevenagel condensation of methylketone derivatives with
methyl cyanoacetate and subsequent treatment of the alpha,beta -unsaturate
d nitriles with sulfur and amine resulted in the corresponding 2-aminothiop
henes 5 or isomers 9 and 10. Reaction of methylketone derivatives bearing a
leaving group at the methyl group under modified Gewald conditions selecti
vely led to the formation of 4-substituted 2-aminothiophenes 9a and 12. The
introduction of the sulfur atom occurs through nucleophilic displacement w
ith sodium sulfide.