Benzimidazoles microwave-assisted synthesis

Benzil, 3 594 14 594 Benzilonium bromide, 4 359t Benzimidazoles, microwave-assisted synthesis of, 16 574-575 Benzimidazolethiols, 25 197 Benzimidazolone dioxazine, 19 446 Benzimidazolone pigments, 19 432 433 Benzimidazolone Violet, pigment for plastics, 7 367t Benzine, 3 597... 

Tu and co-workers [103] have elaborated an efficient microwave-assisted synthesis of 4,5-bis-phenyl substituted benzo[4,5]imidazo[l,2-a]pyrimidines 59 through a MCR of an aromatic aldehyde with 1,2-diphenylethanone and 2-amino-benzimidazole. PEG-300 was used as an inexpensive, nontoxic, and recyclable reaction medium which can be reused up to three times without reduction of the product yield although a weight loss of 10% PEG was observed per cycle (Scheme 43). 

Yu et al. [31] gave the simple and microwave assisted synthesis of pyridinium salts (xxiv) consisting of long alkyl chains and benzimidazole moiety as a blue fluorescent gelators. 

Neochoritis CG, Zarganes-Tzitzikas T, Tsoleridis CA et al (2011) One-pot microwave assisted synthesis under green chemistry conditions, antioxidant screening, and cytotoxicity assessments of benzimidazole Schifif bases and pyrimido[l, 2-a]benzimidazol-3(4H)-ones. Eur 1 Med Chem 46 297-306... 

Abstract Benzimidazole is a biologically important scaffold which displays important biological activities. Recent progress in the synthesis and bioactivity of benzimidazoles is reviewed. New synthetic procedures, including microwave-assisted synthesis, solid phase synthesis, natural product synthesis, and synthesis of bisbenzimidazoles are briefly described. Functionalization and cyclization reactions of benzimidazoles lead to a wide variety of novel benzimidazole structures. Selected bioactivity, such as anti-infective, anti-inflammatory, antitumor and receptor agonist/antagonist activities are presented. 

Recently, microwave-assisted synthesis of eighteen 2-(alkyloxyaryl)-lH-benzimidazole derivatives 20 related to the natural stilbenoid family has been... 

Classical condensation-cyclization reactions using 1,2-diaminobenzenes 24, 2-mercaptoacetic acid 25 and appropriately substituted aromatic aldehydes 26 in dry benzene under reflux required a long reaction time to afford the thiazobenzimidazoles 27, which are potent anti-HIV agents, by Scheme 7. On the other hand, the microwave-assisted synthesis of lH,3H-thiazolo[3,4-a]benzimidazoles 27 was completed in toluene within 12 minutes [32]. 

Conventional synthetic methods remain the mainstream routes for the synthesis of benzimidazoles. However, a few novel synthetic methodologies for the synthesis of benzimidazole have been reported in the time frame selected for this review. The popularity of microwave-assisted synthesis has been increasing rapidly since it enables the effective synthesis of benzimidazoles and its analogs. A wide variety of benzimidazole analogs have been synthesized, and several of these look promising for further drug discovery efforts. 

Boufatah N, Gellis A, Maldonado J, Vanelle P (2004) Efficient microwave-assisted synthesis of new sulfonylbenzimidazoIe-4,7-diones heterocyclic quinones with potential antitumor activity. Tetrahedron 60(41) 9131-9137. doi 10.1016/j.tet.2004.07.070 Brain CT, Brunton SA (2002) An intramolecular palladium-catalysed aryl amination reaction to produce benzimidazoles. Tetrahedron Lett 43(10) 1893-1895. doi 10.1016/80040-4039(02) 00132-6... 

S. Jubie, R. Rajeshkumar, B. Yellareddy, G. Siddhartha, M. Sandeep, K. Surendrareddy, H.S. Dushyanth, K. Elango, Microwave assisted synthesis of some novel benzimidazole substituted fluoroquinolones and their antimicrobial evaluation, J. Pharm. Sci. Res. 2 (2010) 69-76. 

R. Kalirajan, L. Rathore, S. Jubie, B. Gowramma, S. Gomathy, S. Sankar, Microwave assisted synthesis of some novel pyrazole substituted benzimidazoles and evaluation of their biological activities, Indian J. Chem. Sect. B SOB (2011) 1794-1799. 

An efficient and a quick microwave-assisted synthesis of benzimidazoles and trisubstituted imidazoles has been developed by Zhao et al. (2005). Three benzimidazoles were obtained as a result of the condensation of 1,2-phenylenediamine with carboxylic acids and acetoacetic ester without catalyst. A series of trisubstituted imidazoles were synthesized by condensation of benzil, aromatic aldehyde and ammonium acetate in the presence of glacial acetic acid. 

Microwave Assisted Multicomponent Reactions for the Synthesis of Heterocycles Synthesis of benzimidazoles 28 ... 

The one-pot synthesis of thiazolo[3,4-a]benzimidazoles has been reported using a microwave-assisted condensation-cyclization (see Scheme 17) of a substituted 1,2-diamine, substituted benzaldehyde and mercaptoacetic acid [74]. Heating the mixture at reflux for 12 min using a single-mode microwave reactor for the most part gave the fused benzimidazoles in improved yield and dramatically shorter times, when compared to classical conditions of heating at reflux in benzene for 24-48 h (Scheme 29). 

Following the pioneering work by Alterman, several microwave-assisted palladium-catalyzed aminations have been reported for a number of different substrates, using different types of palladium sources and ligands. The examples shown in Scheme 6.59 include bromoquinolines [124], aryl triflates [125], and intramolecular aminations in the synthesis of benzimidazoles [126]. In all cases, the use of micro-wave irradiation dramatically reduced the required reaction times and in many cases also improved the yields. Several authors have also found that the microwave-driven reaction required significantly less catalyst than its conventionally heated counterpart [126]. 

Developing their work on the use of microwave-assisted Niementowski reactions, the same group published the synthesis of novel triaza- and tetraaza-benzo a -indeno[l,2-c]anthracen-5ones by the condensation of anthranilic acid with 2-(2-aminophenyl)indole or benzimidazole (Scheme 3.49)78,79. 

Bendale, P.M. and Sun, C.-M., Rapid microwave-assisted liquid-phase combinatorial synthesis of 2-(arylamino)benzimidazoles, /. Comb. Chem., 2002, 4, 359-361. 

A one-pot microwave-assisted relay reaction for the synthesis of 2-substituted benzimidazoles (xi) have been reported by Pattabiraman et al. [20]. The products were obtained in good yields and the reaction times were significantly reduced. 

Xu and Xong [28] developed a microwave-assisted tracer rapid synthesis of benzimidazoles (xxi) on a polymer support. The arylation of benzylammonia, followed by treatment with N-chlorosulfonyl isocyanate and subsequent hydrolysis gave primary ureas. The Pd-catalysed cyclization of resin bound primary ureas followed by cleavage with TFA-H2O yielded the desired product in good yield and high purities. 

Rheault TR, Donaldson KH, Cheung M (2009) Convenient synthesis of heteroaryl-linked benzimidazoles via microwave-assisted boronate ester formation. Tetrahedron Lett 50 1399-1402... 

Alen J, Robeyns K, Borggraeve WMD, Meervelt LV et al (2008) Synthesis of pyrazino[l, 2-a]benzimidazol-l(2H)ones via a microwave assisted Buchwald-Hartwig type reaction. Tetrahedron 64 8128-8133... 

Several reports of the synthesis and chemistry of benzimidazoles have been published. The most common methods involved the condensation of 1,2-phenylenediamine with a carbonyl group. 2-Substituted benzimidazoles were prepared from 1,2-phenylenediamine and esters under microwave conditions <06SC2597>. A highly selective synthesis of 2-aryl-l-arylmethyl-l/7-1,3-benzimidazoles from the reaction of 1,2-phenylenediamines and aromatic aldehydes in the presence of silica sulfuric acid in ethanol or water has been reported <06TL2557>. Microwave-assisted one-step high-throughput synthesis of benzimidazoles from phenylenediamine and carboxylic acids in the presence of triphenyl phosphite has been disclosed <06TL2883>. A... 

Recently, 2-alkyl- and 2-aryl-substituted benzimidazole derivatives 15 have been synthesized from 1,2-diaminobenzene dihydrochloride 13 and its corresponding acids 14 in the presence of polyphosphoric acid using microwave-assisted methods (Scheme 3). The reaction time required for the synthesis of benzimidazole derivatives 15 was reduced to minutes by this method compared to conventional synthesis, which required up to four hours of heating to complete the reaction. Furthermore, it was found that the application of microwave irradiation increased yields by 10-50% (Table 1). It has been... 

In addition to flow systems that use conventional heating, microwave-assisted flow chemistry has also been reported [78,86-88]. Organ reported the synthesis of benzimidazole through microwave-assisted flow chemistry (Scheme 1.16) [86]. One of the critical components of the flow system was a silicon carbide reactor tube. As mentioned previously, these materials have a very high absorption of microwave radiation and heat very rapidly upon irradiation. The ability of the silicon carbide to transfer heat is also very high thus, this material is ideally suited for the constraction of a reactor tube that wiU be used... 

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