Recent Trends in the Synthesis of Benzimidazoles From o‐Phenylenediamine via Nanoparticles and Green Strategies Using Transition Metal Catalysts

Abstract

Benzimidazole is a heterocyclic moiety of immense importance as it acts as a primary “biolinker” in diverse synthetic routes to obtain bioactive compounds. Substituted benzimidazoles are known to possess a varied range of pharmacological applications, namely, anti‐cancer, anti‐diabetic, anti‐inflammatory, and antiviral like anti‐HIV and anti‐fungal. A number of reviews covering the important aspects of benzimidazoles such as pharmacological activities, SAR studies, and well‐known methods of synthesis have appeared in the literature. However, green synthetic methods particularly using transition metal (TM) catalysts and their nanoparticles, although being more viable and extensively applied by researchers in the present scenario, have not been exclusively and expansively reviewed. Besides this, the vital precursors required for knitting the skeleton of benzimidazole are mainly o‐aryldiamines. The conventional synthesis generally involved the condensation of these diamines with carbonyl/carboxylic acid derivatives either via high temperature heating or via adding strong acids, mostly resulting in poor yields or mixtures. However, recent trends are replacing these conditions by mild and green conditions through TM catalysts. Therefore, the current review emphasizes on the recent trends adopted in the synthesis of benzimidazoles using condensation reaction of o‐phenylenediamines and various aldehydes/ester/amide/alcohols with TM in a catalytic role in nanoform and under environmentally benign green conditions.

t‐BuONa‐Mediated Redox Condensation between o‐Nitroanilines and Benzyl Alcohols towards 2‐Phenyl Benzimidazoles under Transition‐Metal‐Free Conditions

“…All the versatility and superiorities have continually appealed considerable efforts to access substituted benzimidazoles. Annulation of o ‐phenylenediamines with carbonyl compounds such as aldehydes and carboxylic acid derivatives may be the most employed strategies [22–25] . Ortho ‐nitroanilines and benzyl alcohols, which could be converted to two aforementioned starting materials by a redox process, are considered as precursors for the cyclization [26–29] .…”

“…Annulation of o-phenylenediamines with carbonyl compounds such as aldehydes and carboxylic acid derivatives may be the most employed strategies. [22][23][24][25] Ortho-nitroanilines and benzyl alcohols, which could be converted to two aforementioned starting materials by a redox process, are considered as precursors for the cyclization. [26][27][28][29] These synthetic approaches, however, are associated with inherent drawbacks including the requirement of transition metal catalysts, external oxidants, and stoichiometric amounts of acid or base, making them less preferable.…”

Tripodal Triazine and 1,8‐Naphthalimide‐based Small Molecules as Efficient Photocatalysts for Visible‐light Oxidative Condensation

“…[21,45] Therefore, the design of sustainable transition metal-free photocatalysts is highly desirable as it would provide access to non-toxic, earth-abundant, optically tunable candidates to catalyze a wide range of organic transformations. [21,[46][47][48][49] There are few literatures reports on triphenyl triazine based π-conjugated molecules with tunable optical properties, improved light absorption and structural regularity utilized for efficient photoredox reactions [12,50] to synthesize benzimidazole and benzothiazoles. [11,18,37,38,50] High photocatalytic efficiencies and high conversion percentages (up to 99 %) were achieved by triphenyl triazine-based photocatalysts in oxyarylation of alkenes and aerobic oxidation of sulfide to sulfoxide.…”

“…Conventional organic photocatalysts are designed based on transition metal complexes [8,40–44] but those are expensive, toxic and prone to degradation [21,45] . Therefore, the design of sustainable transition metal‐free photocatalysts is highly desirable as it would provide access to non‐toxic, earth‐abundant, optically tunable candidates to catalyze a wide range of organic transformations [21,46–49] …”

A Direct Metal‐Free Synthetic Approach for the Efficient Production of Privileged Benzimidazoles in Water Medium under Aerobic Condition

“…[13] Since the past two decades, several methodologies have been reported with the best of catalytic systems under ambient and near ambient conditions with moderate to excellent yields (Scheme 2). [31,32] Catalysts in such systems included transition and lanthanide metals, [33,34] Lewis acids, [35,36] protic acids, [37] resin-based, [38] crafted nano-materials, [39][40][41] precious metal catalysts, [42] even enzymes [43] with high TON showing excellent results. A variety of solvent systems has also been used with special importance to fluorinated solvents showing a key to the selectivity.…”