Metal-Free Sequential C(sp²)–H/OH and C(sp³)–H Aminations of Nitrosoarenes and N-Heterocycles to Ring-Fused Imidazoles

Abstract

Hydrogen bond assisted ortho-selective C(sp)-H amination of nitrosoarenes and subsequent α-C(sp)-H functionalization of aliphatic amines is achieved under metal-free conditions. The annulation of nitrosoarenes and 2-hydroxy-C-nitroso compounds with N-heterocycles provides a facile excess to a wide range of biologically relevant ring-fused benzimidazoles and structurally novel polycyclic imidazoles, respectively. Nucleophilic aromatic hydrogen substitution (SArH) was found to be preferred over classical SAr reaction during the C(sp)-H amination of halogenated nitrosoarenes.

Incorporating Morpholine and Oxetane into Benzimidazolequinone Antitumor Agents: The Discovery of 1,4,6,9-Tetramethoxyphenazine from Hydrogen Peroxide and Hydroiodic Acid-Mediated Oxidative Cyclizations

“…Common to the oxidative cyclization of o-cyclic amine substituted anilines to give benzimidazoles, 10,28 and the Wohl-Aue and other phenazine syntheses, 19,20,29 is the likelihood of a nitroso-intermediate. Transformations via the N-oxide of the tert-amine of 4a are unlikely, with amine N-oxides isolated intermediates only when the primary NH2 is deactivated to an acetamide.…”

“…The existence of highly reactive nitroso-intermediate 7 is supported by Meth-Cohn, who also refuted claims of isolations of o-nitroso-tert-anilines, including the nitrosation of p-benzyldimethylaniline, which gave only the nitro-compound. 32 Nitroso 7 should undergo a formal 1,5-hydride shift to the likely hydroxylamine 8, 28,[32][33][34] which subsequently cyclizes and is oxidized to give benzimidazole 5a. The unexpected 1,4,6,9-tetramethoxyphenazine (6) formation via nitroso intermediate 7 would involve intermolecular reaction of 7 with starting aniline 4a resulting in nucleophilic aromatic substitution adduct 10.…”

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

“…The nitroso compounds 3 and 6 were synthesized by two different methods. 1-Bromo-3-nitrosobenzene ( 3 ) was obtained by oxidation of 3-bromoaniline ( 2 ) using Oxone ™ (Wegner et al [ 19 – 21 ], Scheme 1 ). Isolation of 3 was achieved, however, a one pot approach including a subsequent Baeyer–Mills reaction to yield 10 is preferred.…”

“… Synthesis of the nitroso compounds 3 and 6 using the two different methods described by Wegner et al [ 19 – 21 ] and Dommaschk et al [ 4 , 27 ]. …”

Synthesis of Mono-N-Methyl Aromatic Amines from Nitroso Compounds and Methylboronic Acid

“…1-Methyl-4-nitrosobenzene ( 1b ), 1-methoxy-4-nitrosobenzene ( 1c ), 1,2-dimethyl-3-nitrosobenzene ( 1d ), 2-nitroso-1,1′-biphenyl ( 1f ), 2,4-dimethoxy-1-nitrosobenzene ( 1g ), 1,3,5-trimethyl-2-nitrosobenzene ( 1h ), 4-nitrosobenzonitrile ( 1i ), methyl 3-nitrosobenzoate ( 1l ), 1-(3-nitrosophenyl)ethanone ( 1m ), 3-nitrosobenzaldehyde ( 1n ), 4-nitrosobenzaldehyde ( 1o ), 1-fluoro-4-nitrosobenzene ( 1p ), 1,2-dichloro-4-nitrosobenzene ( 1q ), 1-iodo-4-nitrosobenzene ( 1s ), N -(3-nitrosophenyl)acetamide ( 1t ), and 4-nitrosodibenzo[ b , d ]thiophene ( 1x ) were prepared following a previously reported procedure starting from the corresponding potassium aryltrifluoroborates. 27 1-Isopropyl-2-nitrosobenzene ( 1e ), 28 2-nitrosobenzonitrile ( 1j ), 29 ethyl 2-nitrosobenzoate ( 1k ), 29 1-bromo-2-nitrosobenzene ( 1r ), 30 (3-nitrosophenyl)methanol ( 1v ), 31 4-methyl-2-nitrosopyridine ( 1y ), 32 and 1-fluoro-2-nitrosobenzene ( 1z ), 33 were prepared following previously reported procedures starting from anilines. 3-Nitrosophenol ( 1u ) 34 and (4-nitrosophenyl)methanol ( 1w ) 35 were prepared following previously reported procedures starting from nitro compounds.…”