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

Abstract

A direct electrochemical synthesis of 1H-substituted benzimidazoles is described. Benzimidazole is a commonly used nitrogen heterocycle in U.S. FDA approved drugs; therefore, a direct and sustainable approach that limits chemical waste for the synthesis of substituted benzimidazoles is appealing. The electrosynthetic approach described within is able to synthesize a variety of 1H-substitubed benzimidazoles while concurrently producing H 2 , without a transition-metal catalyst or added bases. Furthermore, the procedure works efficiently with only simple carbon electrodes, thus avoiding commonly employed platinum and gold electrodes. This electrochemical procedure also exhibited good functional group tolerance. Desired products were achieved with up to 88% yield, illustrating the range and possible sustainability of this approach.

Selective N1-Acylation of Indazoles with Acid Anhydrides Using an Electrochemical Approach

“…To address the challenges of general applicability and operational simplicity while achieving reaction efficiency, we have utilized an electrochemical procedure for the chemoselective acylation of indazoles. This electrochemical procedure, called the “anion pool method” was recently developed by our group for the electrochemical synthesis of alkylated benzimidazoles . The anion pool method builds on principles of the previously developed cation pool method and is base, catalyst, and precious-metal-electrode free.…”

Highly Efficient Zn(L‐Pro)2 Catalyst for the Synthesis of 2‐Phenyl Benzimidazoles and 2‐Phenyl Benzothiazoles via Aerobic Oxygenation

“…[27,29] On the other hand, the traditional method for synthesizing benzothiazoles and benzimidazoles, [30,31] use Brønsted and Lewis acids as catalysts in an oxidative cyclization. Furthermore, the condensation reaction of o-phenylenediamine or o-aminothiophenol with a variety of aldehydes, acid chlorides, carboxylic acids, and nitriles in the presence of a variety of catalytic systems has been developed using Sm(OTf) 3 , [32] Ceric ammonium nitrate [CAN], [33] CeO 2 -ZrO 2 , [34] VOSO 4 , [35] Zn 3 (BTC) 2 MOF, [36] K 2 S 2 O 8 , [37] Bi(NO 3 ) 3 , [38] 4-MethoxyTEMPO, [39] Fe/ionic liquid, [40] Chlorotrimethylsilane, [41] via electrosynthesis, [42] hydrotalcite, [43] and hexamethylenetetramine-bromine complex. [44] While the above-mentioned reports were successfully completed employing a variety of catalysts or reagents, these methods have some drawbacks, including the use of expensive catalysts, toxic reagents and solvents, long reaction times, the formation of side products, the use of strong oxidizing reagents, stoichiometric quantities, and the use of metal salts, all of which are harmful to the environment.…”

“…On the other hand, the traditional method for synthesizing benzothiazoles and benzimidazoles, [30,31] use Brønsted and Lewis acids as catalysts in an oxidative cyclization. Furthermore, the condensation reaction of o‐phenylenediamine or o‐aminothiophenol with a variety of aldehydes, acid chlorides, carboxylic acids, and nitriles in the presence of a variety of catalytic systems has been developed using Sm(OTf) 3 , [32] Ceric ammonium nitrate [CAN], [33] CeO 2 ‐ZrO 2 , [34] VOSO 4 , [35] Zn 3 (BTC) 2 MOF, [36] K 2 S 2 O 8 , [37] Bi(NO 3 ) 3 , [38] 4‐MethoxyTEMPO, [39] Fe/ionic liquid, [40] Chlorotrimethylsilane, [41] via electrosynthesis, [42] hydrotalcite, [43] and hexamethylenetetramine‐bromine complex [44] …”

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

“…K. Bahrami and co‐workers showed an important step forward by using simply water as a solvent in SDS micelle medium and got good yield of the benzimidazole products, but question is to separate the micelle from the solution is always a extra step in this procedure [47] . Furthermore, Vanucci and co‐worker reported an important sustainable route to synthesis a series of 1 H ‐substituted benzimidazole derivatives [48] . They employed a transition‐metal‐free and base‐free electrosynthetic approach based on simple carbon electrodes and produced the benzimidazole scaffold in high yield.…”

“…[47] Furthermore, Vanucci and co-worker reported an important sustainable route to synthesis a series of 1H-substituted benzimidazole derivatives. [48] They employed a transition-metal-free and basefree electrosynthetic approach based on simple carbon electrodes and produced the benzimidazole scaffold in high yield. Therefore, focusing on the limitations associated to produce benzimidazole derivatives, we for the first time, report a catalyst-free synthetic approach to deliver privileged benzimidazoles in an aqueous medium involving aerial oxygen illustrating both air and water playing a pivotal role in the course of synthesis (Scheme 2).…”