Tunable Electrochemical C−N versus N−N Bond Formation of Nitrogen‐Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications

Abstract

Herein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen‐centered radicals (NCRs). By changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C−N versus N−N bond formation reaction. Hence, pyrido[1,2‐a]benzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition‐metal‐ and exogenous oxidant‐free strategy with broad generality. Bioactivity assays demonstrated that pyrido[1,2‐a]benzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.

Directing Group Enables Electrochemical Selectively Meta-Bromination of Pyridines under Mild Conditions

“…17 The success of aminopyridine derivates encouraged us to extend other directing groups (Table 3). The dimethylamino group (NMe 2 ) accomplished the transformation with 73% efficiency (18). Importantly, the primary amines, for instance, cyclohexylamino (NHCy) groups, promoted the reaction in good yields (19).…”

“…It should be pointed out that 2methylaminopyridine gave a relatively low yield (21) because this product would further be dimerized, forming a hydrazine product which was similar to the results of our previous study. 18 Remarkably, the aromatic p-chlorophenylamino (NHAr) group also promoted the desired transformation in 66% yield (20). However, the hydroxyl, methoxy, and acetamide failed to deliver the targeted products (22, 23, and 25).…”

Electrochemical Synthesis of High-Nitrogen Materials and Energetic Materials

“…This was made evident by the research of Chen et al, who studied the generation of C−N intramolecular bonds versus N−N intermolecular bonds from electrochemically generated nitrogen-centered radicals (NCR). 139 The authors hypothesized that by lowering the current density they could force a substituted N-phenyl-pyridinyl amine (72) to undergo intramolecular C−N bond formation to generate species 73 rather than bimolecular N−N coupling to form species 74 (Scheme 10). This is posited from the fact that the current density is proportional to the reaction rate and the concentration of electroactive species near the electrode surface.…”

Electrodimerization of N-Alkoxyamides for the Synthesis of Hydrazines

“…14 Recently, Chen and colleagues presented an electrochemical adjustable methodology from readily available N-2-pyridyl amines, providing easy access to intermolecular N−N coupling and intramolecular C−N bond formation. 15 While outstanding achievements have been accomplished, N−N bond formation from common precursors under electrochemical oxidation conditions is still attractive due to the lack of general electrochemical radical initiation methods to achieve high reaction efficiency. 16 We recognized that the successful realization of the initiation of N-centered radicals from versatile precursors would enable a new N−N bondforming reaction under mild conditions that would allow efficient access to constructing N−N bonds.…”