Thermal and Photoinduced Copper-Promoted C–Se Bond Formation: Synthesis of 2‑Alkyl-1,2-benzisoselenazol-3(2H)‑ones and Evaluation against Mycobacterium tuberculosis

2-Alkyl-1,2-benzisoselenazol-3­(2H)-ones, represented by ebselen (1a), are being studied intensively for a range of medicinal applications. We describe both a new thermal and photoinduced copper-mediated cross-coupling between potassium selenocyanate (KSeCN) and N-substituted ortho-halobenzamides to form 2-alkyl-1,2-benz­iso­selenazol-3­(2H)-ones containing a C–Se–N bond. The copper ligand (1,10-phenan­throline) facilitates C–Se bond formation during heating via a mechanism that likely involves atom transfer (AT), whereas, in the absence of ligand, photoinduced activation likely proceeds through a single electron transfer (SET) mechanism. A library of 15 2-alkyl-1,2-benz­iso­selenazol-3­(2H)-ones was prepared. One member of the library was azide-containing derivative 1j that was competent to undergo a strain-promoted azide–alkyne cycloaddition. The library was evaluated for inhibition of Mycobacterium tuberculosis (Mtb) growth and Mtb Antigen 85C (Mtb Ag85C) activity. Compound 1f was most potent with a minimal inhibitory concentration (MIC) of 12.5 μg/mL and an Mtb Ag85C apparent IC50 of 8.8 μM.