Abstract
Thiophene derivatives are aromatic five-membered ring compounds made up of one sulfur as heteroatom. These compounds are present in a large number of natural and unnatural compounds with valuable bioactivities. Many of them have a wide range of applications in medicinal chemistry such as antimicrobial, anticancer, antiparasitic, anti-inflammatory, and antihypertensive activities. Some of them are famous drugs in the market nowadays such as Cefoxitin, Cephalothin, Cephaloridine, Temocillin, tinoridine, tiaprofenic acid, tenoxicam, suproprofen and Raltitrexed. The use of thiophene derivatives has also been found in other fields. The application of thiophenes in organic materials thanks to their electronic properties has been reported. In organic synthesis, thiophenes have also drawn the attention of chemists because of their values as intermediates. The employment of thiophene derivatives in agrochemicals, flavors, and dyes has also been found. Due to diverse applications, the synthesis of thiophene derivatives has attracted a lot of attention. Numerous known synthetic methods such as Gewald and Fiesselmann methods have been modified and improved. Furthermore, a large number of novel synthetic approaches to the synthesis of thiophenes have been developed. This review will focus on considerable studies on the synthesis of thiophenes which date back from 2012. In this review, we discussed recent achievement in the synthesis of thiophene derivatives. Some established methods have been modified and improved, while other novel methods have been discovered. Diverse catalysts were employed for these transformations. In some syntheses, reaction mechanisms were also displayed. Many methods for the synthesis of thiophenes have been developed recently. In the near future, more imaginative approaches for the synthesis of thiophenes will be investigated to improve the efficiency and versatility or the use of environmentally friendly and economical procedures for thiophene synthesis will be proposed. Application to natural product synthesis and drug synthesis is probably the next challenge in the field.
Keywords: Bioactivity, Gewald reaction, malononitrile, multisubstituted, sulfur, synthesis, thiophenes.
Graphical Abstract