Synthesis of New Substituted Thiophene Derivatives and Evaluating their Antibacterial and Antioxidant Activities

Abstract

p-Fluorophenacyl chloride (1) was used as a building block for the preparation of new tetra-substituted thiophene derivatives. The basic-catalyzed reaction of 1 with various thiocarbamoyl compounds such as 2-acetyl-2-substituted-thioacetanilides 2a,b, 3-arylazo-4-mercapto-4-phenylamino-buten-2-ones 5a–c, ethyl 2-arylazo-3-mercapto-3-phenylamino-acrylates 8a–c, N-aryl-2-cyano-3-mercapto-3-phenylamino-acrylamides 11a–c, N-aryl-2-(mercapto(phenylamino)methylene)-3-oxo-butanamides 14a–c, and 2-mercapto-4,6-dimethylnicotinonitrile 17 led to the production of their corresponding substituted thiophene compounds 4a–b, 7a–c, 10a–c, 13a–c, 16a–c, and 19 in moderate yields. The newly synthesized thiophene compounds were deduced according to FTIR, 1H NMR, 13C NMR, 19F NMR, and mass analyses along with micro-analytical data. The synthesized thiophene compounds were tested to evaluate their antibacterial and antioxidant activities. The majority of the synthesized thiophenes showed good to moderate anti-bacterial and antioxidant activities. The hydroxythiophene compound 4a showed extremely high antibacterial activity with inhibition zones 15–21 mm (from 60 to 87.5% activity indices). It inhibits bacterial growth and approaches the activity of Ampicillin, which inhibits bacteria with areas of inhibition from 23 to 25 mm. The hydroxythiophene compound 4a showed excellent antioxidant properties (85.9%) relative to the reference, Ascorbic acid (88.0%).