Synthesis of substituted indoles through palladium catalyzed and Friedel-Crafts reaction

Abstract

Thesis title: synthesis of substituted indoles through palladium catalyzed and Friedel-crafts reaction. 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 Friedel-Craft acylation reaction. Intramolecular cyclization reaction is reported. In this purpose N-(2-iodo-3/4-substituted phenyl) acetamide 12-15 and 2, 2, 2-trifluoro-N-(2-iodo-4/5-substitutedphenyl) acetamide 16-18 were synthesized by the iodination of their parent 3/4-sustituted anilines using KI, KIO3, HCl in CH3OH. The cross-coupling reaction N-(2-iodo-3/4-substitutedphenyl) acetamide 12-15 and 2, 2, 2-trifluoro-N-(2-iodo-4/5-substitutedphenyl) acetamide 16-18 with trimethylsilylacetyl ene were carried out in the presence of (Ph3P)2PdCl2, CuI, and Et3N in DMF at 60-80°C for24-48 h under nitrogen atmosphere to yield N-(4/5-substituted-2-trimethylesilyl ethynylphenyl) acetamide 19-22 and 2,2,2-trifluoro-N-(4-methyl-2-trimethylesilylethynylphenyl) acetamide 23. The condensed products 19, 21, 22 were subjected to Friedel-Craft acylation by acetyl chloride/ chlorobenzoyl chloride in Cl2CH-CHCl2in presence of anhyd. AlCl3 at 0-25°C for 2 h to yield 1, 2-diacetyl-5-methyl/chloro-1H indoleumchloride 24, 28, 29 and decomposition and difficulties of separation by column chromatography. I got corresponding 4-substituted benzoic acid 25, 26, 27, 30. ----------------------------------