Synthetic Approaches to 2-Arylbenzimidazoles: A Review

Abstract

Benzimidazoles are very useful building blocks for the development of molecules that are important in medicinal chemistry. 2-Substituted benzimidazole derivatives have found applications as diverse therapeutic agents, including antiulcers, antihypertensives, antivirals, antifungals, anticancers, and antihistaminics. Because of their importance, the methods for their synthesis have become a focus of Synthetic Organic Chemists. However, we failed to locate report in the literature that covers various efforts that have been made for the synthesis of 2-arylbenzimidazoles. Therefore, in the present review, we have tried to compile some of the important synthetic techniques and methodologies used for its synthesis during the last decade.

Lithium Hexamethyldisilazane Transformation of Transiently Protected 4-Aza/Benzimidazole Nitriles to Amidines and their Dimethyl Sulfoxide Mediated Imidazole Ring Formation

“…Using p -benzoquinone as an oxidant, 39 scandium triflate 42 or ferric chloride 43 as recyclable oxidants did not improve reaction time or yield of 1a . Although, DMSO is a known oxidant, 44 it does not appear to have been explored in this type of synthesis.…”

“…Indeed, a 2012 review by Panda et al listed 118 different conditions for this synthesis. 39 The first step in this cyclization is the formation of the imine, followed by the cyclic aminal, which is then oxidized to the imidazole ring. We examined the most common conditions to make 1a .…”

Synthesis of 2-arylbenzimidazoles under mild conditions catalyzed by a heteropolyacid-containing task-specific ionic liquid and catalyst investigation by electrospray (tandem) mass spectrometry

“…3 This large spectrum of biological activities shown by a plethora of benzimidazole-based molecules has boosted the development of several synthetic methodologies. 4 Most of those methodologies require, however, toxic solvents, high temperatures, aryl acid chlorides, reagents excesses, large catalysts amounts or other undesired conditions (environmentally maleficent). 5 The development of new catalytic and green chemistry methodologies using eco-friendly and sustainable conditions aiming at better yields, selectivities, and atom economy are therefore highly desired features.…”

Direct conversion of alkyl halides into benzimidazoles using pyridine-N-oxide and 1,2-diaminobenzenes

“…22 Benzimidazoles are usually synthesized by condensation between carboxylic acids or their functional derivatives and o-aminoanilines. [23][24][25][26][27][28] The major drawbacks of these procedures are severe dehydrating reaction conditions, high temperature, considerable reaction time up to one day, and very strong acid catalysts.…”