Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp2 C–H bond activation in ball mills

Abstract

A solvent-free palladium-catalyzed ortho-iodination of acetanilides using N-iodosuccinimide as the iodine source has been developed under ball-milling conditions. This present method avoids the use of hazardous organic solvents, high reaction temperature, and long reaction time and provides a highly efficient methodology to realize the regioselective functionalization of acetanilides in yields up to 94% in a ball mill. Furthermore, the current methodology can be extended to the synthesis of ortho-brominated and ortho-chlorinated products in good yields by using the corresponding N-halosuccinimides.

Keywords

• acetanilide
• ball milling
• C–H activation
• halogenation
• mechanochemistry
• N-halosuccinimide
• palladium catalysis