Synthesis and Anti-inflammatory Evaluation of 2-Aminobenzaldehydes via Ir(III)-Catalyzed C-H Amidation of Aldimines with Acyl Azides

Abstract

The aldimine-directed C-H amidation of various arenes with N-acyl azides as amidation surrogates under cationic iridium(III) catalysis is described. This transformation efficiently provides a range of 2-aminobenzaldehyde derivatives with excellent site selectivity and functional group compatibility. The resulting 2-aminobenzaldehyde framework provides facile access to a range of biologically interesting heterocycles. In addition, all synthetic compounds were screened for anti-inflammatory activity against interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Generally, a range of ortho-amidated benzaldehydes displayed promising inhibitory activity against IL-1β and TNF-α compared to dexamethasone as a positive control. Notably, compounds (3ae and 4ac) were found to exhibit potent anti-inflammatory activity stronger than that of dexamethasone.