Synthesis of indole derivatives through combined palladium catalysed and friedel-crafts reactions

Abstract

In view of tht: extensive natural occurrence and biological importance of the indole nucleus containing heterocyclic compounds a general and facile method for the synthesis of indole derivatives through palladium catalyscd reaction using lrimcthyl silylacetylenc followed by Friedel-Crafts acylation reactions is reported. The heleroannulation reaction was carried out by stirring a mixture of 2- iodoacetanilide 3 and trimethylsilylacelylene m presence of bis(. triphenylphosphenc) palladium(II)chloride as a catalyst, Cu(l)iodidc as a cocatalyst and a base triethylamine. The condensed product was then subjected to Friedel-Crafts acylation reaction with acid chlorides to afford the N-aeyl-2-acyl (Aroyl)-indolium chloride 5-8. S/ VI (P~P~~ ~. DMF, El]N, CuI, NHCOCH] 250 C I 24 h R -CH) -C,!-4 MeO-p -Ph -C6H4 i\1e-p Compound S 67 8 ~COR ~;:'/"0 "'j 0- B (5-8) COCH] ln vitro antimicrobial activity of N-acyl-2-aeyl (Aroyl)indolium chloride 5-8 were evaluated. The N-aeyl-2-aeyl (Aroyl)indolium chloride showed more sensitivity against gram-positive and gram-negative bacteria as wen as human fungal pathogens. Varying substitution at the indole moiety and sub"equent antimicrobial screening identified the C-2-acetyl functionality as a new structural altemativc for optimal antimicrobial property in the indole ela~s of(;ompounds,