New conditions for the synthesis of thiophenes via the Knoevenagel/Gewald reaction sequence. Application to the synthesis of a multitargeted kinase inhibitor

Gewald reaction: synthesis, properties and applications of substituted 2-aminothiophenes

“…However, it is sure, that S 8 has to be activated to react with Knoevenagel-Cope product 9. Some authors report that the activation of sulfur and the following addition of sulfur on a methylene group is base-promoted [57][58][59] , others detail the electrochemical activation of the S 8 .…”

“…66 The yield of a dimer 14 is highly dependent on the reaction conditions. While in some cases the ylidene dimerization is significant and the by-product is isolated in higher yield than the desired 2-aminothiophene derivative 58 , on other hand under suitable reaction conditions not only is the straightforward reaction favored, but also the recyclization of dimerized ylidene 14 to appropriate aminothiophene 7 occurs. 59 The dimer 14 preferably is formed in the less studied, so-called redesigned Gewald procedure which is suitable for preparation six-membered carbonitriles with a free amino group.…”

A Solvent-Free, One-Step, One-Pot Gewald Reaction for Alkyl-aryl Ketones via Mechanochemistry

“…These useful compounds have also been significant with respect to their biological activity [3][4][5]. Due to their importance and versatility, the chemistry of 2-aminothiophenes has received much attention and several synthetic methods have been published [6][7][8].…”

A facile four-component Gewald reaction under organocatalyzed aqueous conditions

“…[20][21][22][23] Another interesting feature of the Gewald reaction is the use of the 2-aminothiophene products in other organic transformations. 24,25 The growing use of MCRs in synthesis led us to examine the possibility of employing more than three components in the reaction so that we can access derivatized Gewald products in a one-pot operation. In the framework of our investigations on the development of one-pot synthetic procedures, [26][27][28] we herein report a simple method for conducting a four-component Gewald reaction under inexpensive and benign aqueous triethylamine conditions.…”