2-Arylbenzimidazoles, synthesis

Brasche and Buchwald developed an efficient Cu(OAc)2-catalyzed substituted benzimidazoles and substituted Af-methyl-2-arylbenzimidazoles synthesis from readily available amidines in good to very good yields (Scheme 8.50). This transformation proceeds via direct C-H bond functionalization and C-N bond formation. The O2 was used as the oxidant and water was generated as the only by-product. The starting material amidines were prepared easily from anilines with carbonitrile derivative in advance [89]. 

In addition to the synthesis of industrially important azo dyes using heteroaromatic diazo components, intramolecular azo coupling reactions of heterocyclic diazonium ions also have interesting synthetic uses, because they lead to new fused-ring heterocycles, as shown by the diazotization of 2-amino-3-arylbenzimidazoles (12.7) in which, without isolation of the diazonium ion, a 1,2,4-triazine ring is formed (Kolodyazhnaya et al., 1973). Further examples of intramolecular azo couplings were reviewed by Tisler and Stanovnik (1980), and very extensively (403 references ) by Kishimoto et al. (1990). 

Perry RJ, Wilson BD (1993) A novel palladium-catalyzed synthesis of 2-arylbenzimidazoles. J Org Chem 58 7016-7021... 

Savall BM, Eontimayor JR (2008) Synthesis of 2-arylbenzimidazoles via microwave Suzuki-Miyaura reaction of unprotected 2-chlorobenzimidazoles. Tetrahedron Lett 49 6667-6669... 

Joshi, R. S., Mandhane, P. G., Dabhade, S. K. and Gill, C. H. 2010. Tetrabutylammonium fluoride (TBAF) catalysed synthesis of 2-arylbenzimidazole in water under ultrasound irradiation. 7. Chin. Chem. Soc. 57 1227-1231. 

Skraup synthesis. It has now been reported that a convenient and cost effective preparative method results by using silver-loaded titania as the photocatalyst. In a similar way, n-nitroanilines are reduced to 1,2-phenylendiamines on Pt-loaded Xi02. Under these conditions condensation and dehydrogenation ensue leading to 2-arylbenzimidazoles in a convenient one-pot procedure that combines catalysis and photocatalysis (see Scheme 4). °... 

Sahu, D. P. Iodine-mediated synthesis of 2-arylbenzoxazoles, 2-arylbenzimidazoles, and 1,3,5-tiisub-stituted pyrazoles. Synth. Commun. 2006, 36, 2189-2194. 

An efficient and simple synthesis of several 2-arylbenzimidazoles from the reaction of 4-methyl-l,2-phenylenediamine and aromatic carboxyhc acids in the presence of zeolite catalyst is reported. The reactions were performed nnder MW irradiation, and the catalyst could be recycled and used for several times [103] (Scheme 3.43). 

Scheme 3.43 Synthesis of several 2-arylbenzimidazoles usong green method...

For the synthesis of 2-arylbenzimidazoles 8, cyclocondensation of o-phenylenediamines with aryl aldehydes followed by C-N-dehydrogenation of the primarily formed benzimi-dazolines 7 is frequently used ... 

The previous catalysts were adapted for the ruthenium-catalysed benzimidazoi-soquinoline synthesis via oxidative coupling of 2-arylbenzimidazoles with alkynes. Thus [RuCl2(p-cymene)]2, with 0.5-2 equiv. of Cu(0Ac)2.H20 in toluene at reflux produced a variety of benzimidazoisoquinolines. Unsymmetrical alkynes such as phenylpropionate led to the regioselective insertion with (Ph)C-C bond formation [(Eq. 91)] [180]. As an attempt to recover the catalyst, reactions were performed in PEG-400 as a solvent medium and the products were obtained in similar yields as in toluene and the catalyst could be recycled a few times [(Eq. 91)]. 

K. Khosravi, S. Kazemi, Synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles in both room temperature and microwave condition catalyzed by hexamethylenetetramine-bromine complex, Chin. Chem. Lett. 23 (2012) 61-64. 

D. Saha, A. Saha, B.C. Ranu, Remarkableinfluenceof substituent in ionic liquid in control of reactions simple, efficient and hazardous organic solvent free procedure for the synthesis of 2-arylbenzimidazoles promoted by ionic Kquid, [pmim]BF4, Green Chem. 11 (2009) 733-737. 

Alkoxyaniline units have been used as traceless linkers for the solid-phase combinatorial synthesis of 2-arylbenzoxazoles, 2-arylbenzothioazoles, and 2-arylbenzimidazoles [40] (Scheme 18). This method has an added advantage as the products can be released from the solid support only by exposing it to an air atmosphere without any kinds of oxidants under neutral conditions. The solid support could be easily recovered and recycled after cleavage. 

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