Site-selective and metal-free C–H nitration of biologically relevant N-heterocycles

Abstract

The site-selective and metal-free C–H nitration reaction of quinoxalinones and pyrazinones as biologically important N-heterocycles with t-butyl nitrite is described. A wide range of quinoxalinones were efficiently applied in this transformation, providing C7-nitrated quinoxalinones without undergoing C3-nitration. From the view of mechanistic point, the radical addition reaction exclusively occurred at the electron-rich aromatic region beyond electron-deficient N-heterocycle ring. This is a first report on the C7–H functionalization of quinoxalinones under metal-free conditions. In contrast, the nitration reaction readily takes place at the C3-position of pyrazinones. This transformation is characterized by the scale-up compatibility, mild reaction conditions, and excellent functional group tolerance. The applicability of the developed method is showcased by the selective reduction of NO2 functionality on the C7-nitrated quinoxalinone product, providing aniline derivatives. Combined mechanistic investigations aided the elucidation of a plausible reaction mechanism.

Tandem annulation and dipolar cycloaddition of azomethine imines in catalytic C(sp2)–H functionalization

“…18,19 In addition, the photocatalytic reaction of azomethine imines for the formation of C-centered radicals, which are trapped by various electrophiles, has been reported. 20,21 With the current advances in transition metal-catalyzed [22][23][24][25][26][27][28][29] and transition metal-free [30][31][32][33] C-H functionalization, azomethine imines have been employed in catalytic C-H functionalization, such as alkylation and alkynylation. 34,35 Considering the increase in demand for the construction of novel polycyclic N,O-heterocycles in medicinal chemistry and drug discovery, 36,37 research efforts have recently been dedicated to C-H functionalization and dipolar cycloaddition performed in tandem.…”

“…In addition, the photocatalytic reaction of azomethine imines for the formation of C ‐centered radicals, which are trapped by various electrophiles, has been reported 20,21 . With the current advances in transition metal‐catalyzed 22–29 and transition metal‐free 30–33 C–H functionalization, azomethine imines have been employed in catalytic C–H functionalization, such as alkylation and alkynylation 34,35 …”

Site-selective direct nitration of 2H-indazoles: easy access to 7-nitroindazoles

“…Based on the aforementioned control experiments and the previously related literature reports, 5 a ,14,15 a possible mechanistic pathway for this strategy has been proposed in Scheme 4. At first, a reactive NO 2 radical species ( I ) is generated upon thermal decomposition of Fe(NO 3 ) 3 ·9H 2 O.…”