Synthesis of 1,2-Fused/Disubstituted Benzimidazoles and Benzimidazolium Salts by I₂-Mediated sp³ C–H Amination

Abstract

An intramolecular sp 3 C−H amination reaction of aniline derivatives has been established. This reaction employs molecular iodine (I 2 ) under transition-metal-free conditions and produces 1,2-fused or 1,2-disubstituted benzimidazoles. This operationally simple synthetic process works well with N-substituted aniline substrates, forming novel benzimidazolium frameworks. Under the optimal reaction conditions, a broad variety of 1,2fused/disubstituted benzimidazoles and benzimidazolium salts, including several bioactive compounds, were synthesized from readily accessible precursors in an efficient and scalable fashion.

Manganese‐catalyzed Efficient Synthesis of N‐heterocycles and Aminoketones Using Glycerol as a C3 Synthon

“…Full experimental details for preparing catalysts and dehydrogenation coupling reaction, spectroscopic and chromatogramphic data of all compounds, are available in the Supporting Information of this article. The authors have cited additional references within the Supporting Information [53–66] …”

Thermocatalytic Conversion of CO2 to Valuable Products Activated by Noble‐Metal‐Free Metal‐Organic Frameworks

“…Benzimidazoles and its derivatives are important N-containing heterocyclic compounds due to their pharmacological properties and biological activities, which can be synthesized by condensation of 1,2-phenylenediamines and carboxylic acid based on the Ladenburg ring closure method. [200] Utilization of CO 2 as C1 source is another environmentally friendly method to synthesize benzimidazoles, but efficient catalysts are highly desired due to the inert CO 2 . Frustrated Lewis pairs (FLPs) consist of sterically hindered Lewis bases and Lewis acids, which exhibit excellent ability for nonmetal-mediated activation of CO 2 .…”

Recent Advancements in Strategies for the Synthesis of Imidazoles, Thiazoles, Oxazoles, and Benzimidazoles

“…(2023) devised a transition metal‐free, molecular iodine‐catalyzed intramolecular Sp 3 C−H amination reaction of N‐substituted aniline derivatives for the efficient synthesis of pharmaceutically important scaffolds of benzimidazoles having fused and di‐substituted ring structures (Scheme 143). [167] The N‐substituted aniline scaffolds were synthesized from 2‐fluronitrobenzene in the presence of amine, followed by the reduction of the nitro group. This novel synthetic procedure involving oxidative cyclization in the presence of molecular iodine and sodium acetate as base has broad functional group tolerance and is acquiescent to gram‐scale synthesis.…”

“…At first, AlCl 3 does activate the fluoride, followed by the concurrent attack of the NH group on the carbon of the CHF 2 group, which generates the ). [167] The N-substituted aniline scaffolds were synthesized from 2-fluronitrobenzene in the presence of amine, followed by the reduction of the nitro group. This novel synthetic procedure involving oxidative cyclization in the presence of molecular iodine and sodium acetate as base has broad functional group tolerance and is acquiescent to gram-scale synthesis.…”