Abstract:
Indole derivatives are one of the most privileged structure motifs frequently found in natural products, pharmaceuticals, functional materials, and agrochemicals. Synthesis and biological evaluation of indole derivatives have been a topic of special interest to organic and medicinal chemist. Here a convenient method for the synthesis of 2, 5-disubstituted indole derivatives through palladium catalyzed cross-coupling reaction followed by base catalyzed and palladium catalyzed intramolecular cyclization reaction is reported. In this purpose, 2-iodo-4-substituted-N-ethanoyl anilines 4, 7 were synthesized by the iodination of their parent 4-sustituted anilines using I2, (CH3COO)2Cu in CH3COOH. The cross-coupling reaction of 2-iodo-4-substituted-N-ethanoyl anilines 4, 7 with terminal alkynes 11-13 were carried out in the presence of (Ph3P)2PdCl2, CuI, and Et3N in DMF at 60-80°C for 24-48 h under nitrogen atmosphere to yield 2-alkynyl-4-substituted-N-ethanoyl anilines 14-18. The condensed products 14, 15, 17 were subjected to base catalyzed cyclization by EtONa in EtOH at 80°C for 4-6 h to yield 2, 5-disubstituted-1H indoles 20, 22 along with acyclic by products 2-alkynyl-4-substituted anilines 21, 23, 24. The condensed products 15-17 were also subjected to intramolecular cyclizaton by PdCl2 in CH3
CN at 80°C for 0.5-2 h to yield 2, 5-disubstituted –N-ethanoyl indoles 25-27 only.
In vitro antimicrobial activities of the synthesized compounds 4, 7, 14-18, 25-27 were evaluated. None of the compound showed inhabitant activity against the gram positive and gram negative bacteria as well as human fungal pathogens.
