Copper-Catalyzed Double C–N Bond Formation for the Synthesis of Diverse Benzimidazoles from N-Alkyl-2-iodoaniline and Sodium Azide

Abstract

An efficient approach to the synthesis of benzimidazole derivatives has been achieved by copper-catalyzed double C-N bonds formation of N-alkyl-2-iodoaniline and sodium azide. The reaction was supposed to proceed through copper-catalyzed tandem reaction of S N Ar reaction, aerobic oxidation of C(sp 3 )-H bond and intramolecular C-N bond formation sequence. Structurally diverse 2-aryl, alkenyl and alkyl benzoimidazole derivatives were assembled by this methodology.

Transition-Metal-Free and Base-Free Electrosynthesis of 1H-Substituted Benzimidazoles

“…Further exploration on the reactivity of benzylic halides with benzimidazoles was undertaken due to their prevalence in medicinal compounds. Numerous protocols for the synthesis of benzyl benzimidazoles have been developed, which typically require the use of excess base and elevated temperatures. − Further, some reports indicate that debenzylation can lead to loss of products under similar conditions in the presence of a base. , Other catalytic procedures for the synthesis of benzyl benzimidazoles require transition-metal catalysts. ,,, A base-free and transition-metal-free procedure, however, has yet to be reported.…”

“…Moreover, competing side reactions of carbon electrophiles, such as dehydrohalogenation, might also limit benzimidazole functionalization. The conventional procedures may also lead to overalkylation of benzimidazole-producing quaternary salts . In addition, stoichiometric quantities of waste are generated from the used base in the reaction.…”

“…The conventional procedures may also lead to overalkylation of benzimidazole-producing quaternary salts. 11 In addition, stoichiometric quantities of waste are generated from the used base in the reaction.…”

Formation of Amidinyl Radicals via Visible-Light-Promoted Reduction of N-Phenyl Amidoxime Esters and Application to the Synthesis of 2-Substituted Benzimidazoles

“…Chromatography (petroleum ether/EtOAc 10:1–8:1), white solid, 41.6 mg, yield 77%, mp > 300 °C (lit. : mp 290–292 °C). 1 H NMR (400 MHz, DMSO- d 6 ) δ 13.01 (s, 1H), 8.30 (d, J = 8.0 Hz, 2H), 7.89 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 7.2 Hz, 2H), 7.74–7.36 (m, 5H), 7.24 (s, 2H).…”

“…Furthermore, the necessary substituted o -phenylenediamines are often difficult to prepare. An alternative method involving oxidative cyclocondensation of o -phenylenediamines with primary amines, alcohols, halides, and even methylarenes has been recently reported, but this method also requires harsh reaction conditions. Thus, a mild, environmentally friendly method for synthesizing benzimidazoles remains to be developed.…”