Palladium (0) catalyzed Suzuki cross-coupling reactions of 2,4-dibromothiophene: selectivity, characterization and biological applications

Abstract

A series of novel 2-aryl1-4-bromothiophenes (2a–f), biarylthiophenes with non-identical aryl groups (3a–e) and biarylthiophenes with identical aryl groups (4a–f) were synthesized in moderate to excellent yields by using different arylboronic acids in a Suzuki–Miyaura cross-coupling reaction. The experimental results showed that the use of K2CO3 as base resulted in moderate yields compared with that of good yields obtained upon using K3PO4. The highest yield obtained using K3PO4 was 82% for 2, 4-bis (4-chlorophenyl) thiophene (4d). The synthesized compounds in the present study were examined for their biofilm inhibition and hemolysis assay. Among all compounds 2, 4-bis (4-methoxyphenyl) thiophene (4b) was found to strongly inhibit the formation of bacterial biofilm against E. coli. The compound 4b exhibited higher inhibition (80.92%) compared with the standard Rifampicin with 97.43% inhibition. The compound 2, 4-bis (4-chlorophenyl) thiophene (4d) displayed strong anti-biofilm activity with its ability to prevent the formation of Pasteurell amultocida biofilm at the percent inhibition of 74.53%. In addition, 2f showed the highest percentage hemolysis 16.0% compared with that of the standard Triton-X-100. 3