Tracking the Process of Domino Ring-Opening and Coupling of Fused Imidazole and Direct Observation of Peroxide Intermediates

Comprehensive SummaryA domino ring-opening and coupling of imidazolyl annulated heterocycles 1 (1a: 4-methyl-1-(1-methyl-1H-benzo[d]imidazol-2-yl)-4H- benzo[d]imidazo[1,5-a]imidazole, 1b: 1-(1,5-dimethyl-1H-benzo[d]imidazol-2-yl)-4,7-dimethyl-4H-benzo[d]imidazo[1,5-a]imidazole) with dioxygen was developed at solvothermal condition, leading to conjugated 1,2-diamidoalkenes derivatives 2 ((E)-ArCONHArC=CArNHCOAr (Ar: 1-methyl-1H-benzo[d]imidazolyl (2a), 1,5-dimethyl-1H-benzo[d]imidazolyl (2b))) as single crystals directly. The reaction process was tracked by electrospray ionization mass spectrometry (ESI-HRMS) and a series of reaction intermediates are detected. O-18(2) labeling experiment verified the source of oxygen in 2. Combining evidence from control experiments, nuclear magnetic resonance (NMR) tracking, and crystallography, a seven-step reaction pathway involving oxygen addition, ring opening, Friedel-Crafts alkylation, oxidation, and dehydration was proposed and further supported by DFT calculation.

Automated summary

A domino ring-opening and coupling reaction of imidazolyl annulated heterocycles was developed using dioxygen under solvothermal conditions, resulting in the formation of conjugated 1,2-diamidoalkenes derivatives. The reaction pathway involving oxygen addition, ring opening, Friedel-Crafts alkylation, oxidation, and dehydration was proposed and supported by various experimental techniques.