Efficient synthesis of 2-phenyl-3-substituted furo/thieno[2,3-b]quinoxalines via Sonogashira coupling reaction followed by iodocyclization and subsequent palladium-catalyzed cross-coupling reactions

Abstract

In this paper, we report the successful synthesis of new 2-phenyl-3-substituted furo/thieno[2,3-b]quinoxaline derivatives from 2-chloro-3-methoxyquinoxaline and 2-chloro-3-(methylthio)quinoxaline by a three-step approach. The Sonogashira coupling reaction of the title compounds with terminal alkynes afforded 2-methoxy-3-(phenylethynyl)quinoxaline and 2-(methylthio)-3-(phenylethynyl)quinoxaline in good to excellent yields. The iodocyclization of the resulting compounds using ICl in CH₂Cl₂ afforded 3-iodo-2-phenylfuro[2,3-b]quinoxaline and 3-iodo-2-phenylthieno[2,3-b]quinoxaline. The subsequent palladium-catalyzed Sonogashira, Suzuki, and Heck reactions of the resulting iodo compounds led to the formation of 2,3-disubstituded furo/thieno[2,3-b]quinoxaline in high yields. All compounds were fully characterized by FT-IR, mass, ¹H NMR, and ¹³C NMR spectral data. The synthesized quinoxaline derivatives were also screened against the two bacterial strains Escherichia coli and Micrococcus luteus.