Synthesis of benzo[4,5]imidazo[1,2-a]quinoxalines by I₂-mediated sp³ C–H amination

Abstract

Benzo[4,5]imidazo[1,2-a]quinoxaline derivatives were synthesized from readily accessible 2-(benzoimidazol-1-yl)aniline substrates by an I2-mediated direct sp3 C−H amination reaction. This synthetic strategy does not use transition-metals, is operationally simple and scalable, and...

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

“…On the basis of these experimental results and our previous work on I 2 -mediated C–H amination, tentative mechanisms are proposed for the formation of these benzimidazole and benzimidazolium products and are shown in Scheme . Taking the synthesis of 2a as an example, base-promoted iodination of aniline substrate 1a first generates a plausible N -iodo species ( B ).…”

“…In view of the importance of 1,2-fused/disubstituted benzimidazoles, new and practical synthetic approaches to access compounds of this type are still highly desirable and should benefit the drug discovery field. Continuing our research interest in iodine-mediated C–H amination, we report herein a facile and efficient sp 3 C–H amination reaction promoted by molecular iodine for the synthesis of 1,2-fused/disubstituted benzimidazoles from readily accessible aniline derivatives under transition-metal-free conditions. This synthetic process also works well with N -substituted aniline substrates, producing novel benzimidazolium salts, which previously could only be accessed by further alkylation or arylation of the preformed benzimidazole skeletons …”

Imidazoquinoxaline as a Privileged Fused Pharmacophore in Anticancer Drug Development: A Review of Synthetic Strategies and Medicinal Aspects

“…In 2020, Chen and the group reported I 2 -mediated sp 3 CÀ H amination for the synthesis of imidazo[1,2a]quinoxalines. [35] The reported method was free from metals, scalable, and compounds were obtained in high yield. Huang et al utilized metal catalyst copper for the synthesis of imidazo[1,2-a]quinoxaline derivatives from methylbenzenesulfonamides ( 5) and benzoimidazole derivatives (6).…”

“…There are multiple developments reported for the synthesis of imidazo[1,2‐a]quinoxalines which are described in Figure 3. In 2020, Chen and the group reported I 2 ‐mediated sp 3 C−H amination for the synthesis of imidazo[1,2‐a]quinoxalines [35] . The reported method was free from metals, scalable, and compounds were obtained in high yield.…”

Cobalt-Catalyzed Isocyanide-Based Three-Component Cascade for the Synthesis of Quinazolines

“…In addition, compounds containing a quinazoline framework ( IV and V ) were known to exhibit anti-inflammatory and antitumor activities . Hence, various procedures for the assembly of the quinazoline core have been developed. − However, the existing methods show lower atom and step economy and often suffer from a limited substrate scope. Thus, development of a concise, highly efficient, environmentally benign, and economically acceptable method is highly desirable.…”