Ultrasound Assisted alpha-Arylation of Ketones: A Rapid Access to Isoquinolinone Derivatives

摘要

In the current study we have demonstrated the effectiveness of ultrasound, a source of green energy, in accessing various isoquinolin-1(2H)-one derivatives via the sequential two-step reaction in a single pot. The methodology involved ultrasound assisted Cu-catalyzed alpha-arylation of ketones with 2-iodobenzamide (via a C-C bond formation) followed by intramolecular cyclization (via the C-N bond formation) in the same pot. The role of ultrasound, catalyst, base and solvent in the current transformation was evaluated and the generality as well as scope of the methodology was examined via synthesizing a variety of compounds in acceptable to good (49-93 %) yields. The application potential of the methodology was demonstrated further via synthesizing a reported bioactive arylisoquinolinamine derivative of medicinal significance. Further, the encouraging inhibition of TNF-alpha in vitro (>50 % at 10 mu M) was shown by some of the synthesized compounds e. g. 3 j, 3 m and 3 p.