A Practical Transition Metal-Free Synthesis of Highly Substituted Thiophenes Containing a Benzoxazole Moiety and Their Antimicrobial Activity

Abstract

Two new series of 3-(pyrrol-1-yl)thiophene derivatives 3a–3c and 3-amino-4-(1,3-benzoxazol-2-yl)-5-(substituted-amino)thiophene derivatives 5a–5f were synthesized in 75–85% and up to 91% yields, respectively, from readily available and simple substrates. Substrates 2a–2c underwent an amino group change into a pyrrole unit on heating in acetic acid. This protocol has been proven effective by a scaled-up reaction and synthetic transformation. The functional group tolerance and substrate scope of this approach were both approved. It was also possible to prepare substituted thiophenes in a single process. The synthesized thiophene derivatives were tested for their antibacterial effects. The results showed that the presence of a ketone group on the thiophene unit was more efficient compared to the ester group. Compounds 2c, 5b, and 5c showed higher antibacterial activity against both Gram-positive and Gram-negative bacteria. Particularly, compound 5b exhibited the highest antibacterial activity with a MIC value of 0.0625 mg/mL against Staphylococcus aureus, Escherichia coli, and Candida albicans and with a MIC value of 0.125 mg/mL for Bacillus subtilis, Salmonella enterica, and Pseudomonas aeruginosa.