N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

• Ismail Özdemir,
• Nevin Gürbüz,
• Nazan Kaloğlu,
• Öznur Doğan,
• Murat Kaloğlu,
• Christian Bruneau and
• Henri Doucet

Beilstein J. Org. Chem. 2013, 9, 303–312, doi:10.3762/bjoc.9.35

• chlorides can be promoted by N-heterocyclic carbene ligands associated to palladium. So far, the reason for the influence of the nature of the carbene ligand on such couplings remains unclear. However, the presence of bulky N-substituents on the benzimidazole ring, such as 3,5-di-tert-butylbenzyl (1–4) or

From bead to flask: Synthesis of a complex β-amido-amide for probe-development studies

• Kevin S. Martin,
• Cristian Soldi,
• Kellan N. Candee,
• Hiromi I. Wettersten,
• Robert H. Weiss and
• Jared T. Shaw

Beilstein J. Org. Chem. 2013, 9, 260–264, doi:10.3762/bjoc.9.31

• Medicine, University of California, Davis, Medical Center, Sacramento, CA 95817, USA UC Davis Comprehensive Cancer Center, 2279 45th Street Sacramento, CA 95817, USA 10.3762/bjoc.9.31 Abstract A concise synthesis of benzimidazole-substituted β-amido-amide LLW62 is presented. The original synthesis of

• step involves the use of a β-amino acid-forming three-component reaction (3CR), the scope of which defines its role in the synthetic strategy. Keywords: β-amino acid; benzimidazole; multicomponent reaction; Introduction Library syntheses and high-throughput screening can often be combined to enable

• chemical and radiation therapy by subverting this p21-mediated DNA repair process [14][15][16][17]. In this study, we developed a synthesis of LLW62 (1, Figure 2), which is a complex benzimidazole-substituted β-amido-amide similar in structure to inhibitors of p21 that were reported previously to support

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA 10.3762/bjoc.9.23 Abstract High-throughput screening (HTS) previously identified benzimidazole 1 (JMN3-003) as a compound with broad antiviral activity against different influenza viruses and paramyxovirus strains. In pursuit of a lead

• : asymmetric synthesis; benzimidazole; host-directed; myxovirus; small molecule inhibitor; Introduction Myxoviruses are divided into two evolutionarily distinct yet related families: the orthomyxoviridae, which is composed largely of the influenza viruses, and the paramyxoviridae, which includes respiratory

• -molecule antiviral hits resident in host cells [13]. One such molecule recently described is benzimidazole 1 [14] (Figure 1). Although the compound is active in vitro against a number of different para- and orthomyxoviruses, 1 has poor water solubility (<15 μg/mL), which may contribute to its low oral

C2-Alkylation of N-pyrimidylindole with vinylsilane via cobalt-catalyzed C–H bond activation

• Zhenhua Ding and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2012, 8, 1536–1542, doi:10.3762/bjoc.8.174

• Cl) and electron-donating (OMe) substituents and steric hindrance at the C3 and C7 positions. Unlike the cobalt-catalyzed C2-alkenylation reaction (Scheme 1a) [33], the reaction did not tolerate a cyano group on the indole substrate. In addition, N-pyrimidyl benzimidazole did not participate in the

Synthesis of new pyrrole–pyridine-based ligands using an in situ Suzuki coupling method

• Matthias Böttger,
• Björn Wiegmann,
• Steffen Schaumburg,
• Peter G. Jones,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2012, 8, 1037–1047, doi:10.3762/bjoc.8.116

• substructures of common neutral ligands used in europium complex chemistry [6][9]: 2,2’-bipyridine and 1,10-phenanthroline. Compound 3 comprises a benzimidazole heterocycle, which was also used by the Bünzli group [1][2][3][4]. The synthesis of the resulting complexes was to date unsuccessful. We report here on

• literature procedure [12]. Compound 9 was synthesized by principally the same reaction path [12][13]. 2-Bromopyridine-6-benzimidazole 10 was published in a patent [14], and its preparation was adapted from [4]. The following in situ Suzuki coupling uses Boc-protected pyrrole [15], which was subjected to

• is ca. 3.35 Å. The structure of the ethanol solvate of compound 3 is shown in Figure 5. The central ring is almost coplanar with the pyrrole ring (interplanar angle 9°), but subtends an angle of 38° with the benzimidazole system. Ethanol forms one classical hydrogen bond within the asymmetric unit

Hybrid super electron donors – preparation and reactivity

• Jean Garnier,
• Douglas W. Thomson,
• Shengze Zhou,
• Phillip I. Jolly,
• Leonard E. A. Berlouis and
• John A. Murphy

Beilstein J. Org. Chem. 2012, 8, 994–1002, doi:10.3762/bjoc.8.112

• ][23][24][25][26][27]. Benzimidazole-derived donor 1 converted aryl iodides to aryl radicals by transfer of a single electron at 110 °C [17], and was the first neutral organic ground-state molecule to achieve this. Later, the more powerful reagents 2 [18], 4 [20] and 5 [21] and related compounds [25

• in Figure 1, while the pre-existing aromatic rings in 6 are represented in red. The driving force for oxidation arising through aromatisation is greater for the imidazole- and pyridine-derived motifs 7 and 8, which are associated with the strongest donors, than it is for the benzimidazole-derived

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• 99% yield. Cyclization of 12 in the presence of triethyl orthoformate and a catalytic amount of TsOH at 80 °C gave the corresponding benzimidazole derivative 13 in 76% yield, which was further treated with (S)-2-amino-2-phenylethanol in the presence of Cs2CO3 in toluene to afford the corresponding

• were easily isolated by silica gel column chromatography in 37% yield and 44% yield, respectively. Similarly, using L-valinol, (Sa,S)-15b and (Ra,S)-15b could also be synthesized. Quaternization of the benzimidazole ring of (Sa,S)-15 and (Ra,S)-15 with R2I (R2 = Me, Et) gave the corresponding

• thermal ellipsoids at the 30% probability level. Selected bond distances (Å) and angles (°): Au1–I1 2.5260(5), Au1–C7 1.991(5), C7–N1 1.334(7), C7–N2 1.357(7), N2–C14 1.427(6), I1–Au1–C7 173.12(16), Au1–C7–N2 124.5(4), C7–N2–C14–C15 105.8(6). Synthesis of axially chiral benzimidazole derivatives. The

Derivatives of phenyl tribromomethyl sulfone as novel compounds with potential pesticidal activity

• Krzysztof M. Borys,
• Maciej D. Korzyński and
• Zbigniew Ochal

Beilstein J. Org. Chem. 2012, 8, 259–265, doi:10.3762/bjoc.8.27

• some nitroaniline and benzimidazole derivatives was beneficial to their herbicidal and fungicidal activity [6][8][9]. Moreover, some 2-nitroaniline and 2,6-dinitroaniline derivatives belong to the group of commonly applied herbicides [10]. Herein we report the synthesis of novel aromatic compounds

• containing a tribromomethylsulfonyl group, including derivatives of nitroaniline, nitrophenylhydrazine, diphenyl ether and benzimidazole (Scheme 1). All the target molecules are derived from a common precursor, namely 4-halogenphenyl tribromomethyl sulfone, efficiently synthesized from inexpensive 4

• hydroxide, the particular products being later successfully isolated by recrystallization. With diamine 9 at hand, we proceeded to the synthesis of benzimidazole scaffolds (Scheme 7, Table 3; see Supporting Information File 1 for further details on products 11a–11j). The cyclization was carried out

Imidazole as a parent π-conjugated backbone in charge-transfer chromophores

• Jiří Kulhánek and
• Filip Bureš

Beilstein J. Org. Chem. 2012, 8, 25–49, doi:10.3762/bjoc.8.4

• represents another synthetic approach used for the synthesis of superior diimidazole chromophores [20]. Benzimidazole D-π-A derivatives are a well-investigated class of charge-transfer chromophores. Although many synthetic approaches are known to date [10][21][22], the most popular ones involve the

• −30 esu) showed a substantially higher dipole moment and first-order hyperpolarizability than chromophore 27a (Figure 9; μ = 10.9 D; β = 50.91 × 10−30 esu) due to a higher efficiency of D-A conjugation. Benzimidazole-derived chromophores In contrast to imidazoles, benzimidazoles possess fused benzene

• inexpensive and readily available compounds (Scheme 1). Typical representatives of benzimidazole-derived D-π-A systems are shown in Figure 11. In 2004, Carella, Centore, and co-workers [25] reported the synthesis and further application of nitrobenzimidazole-derived anilines 35 and 36. These two compounds

Gold-catalyzed oxidation of arylallenes: Synthesis of quinoxalines and benzimidazoles

• Dong-Mei Cui,
• Dan-Wen Zhuang,
• Ying Chen and
• Chen Zhang

Beilstein J. Org. Chem. 2011, 7, 860–865, doi:10.3762/bjoc.7.98

• to form α-diketones and aldehydes in good yields is presented. Further directed synthesis of quinoxalines and benzimidazoles, via the condensation of the resulting α-diketones and aldehydes with benzene-1,2-diamine, was achieved in high yields. Keywords: allene; benzimidazole; gold-catalysis

• interested in the use of gold for simple and highly efficient transformations. Additionally, quinoxaline and benzimidazole skeletons are common building blocks for the preparation of substances with pronounced biological activities [39][40][41][42][43][44]. Herein, we report the gold(I)-catalyzed oxidation

Synthesis of chiral mono(N-heterocyclic carbene) palladium and gold complexes with a 1,1'-biphenyl scaffold and their applications in catalysis

• Lian-jun Liu,
• Feijun Wang,
• Wenfeng Wang,
• Mei-xin Zhao and
• Min Shi

Beilstein J. Org. Chem. 2011, 7, 555–564, doi:10.3762/bjoc.7.64

• desired compound (S)-2a in 98% yield. Reduction of (S)-2a by means of Pd-C/H2 for 8 h gave (S)-3a in 98% yield. Subsequent cyclization with triethyl orthoformate catalyzed by p-toluenesulfonic acid at 100 °C for 5 h afforded (S)-4a in 83% yield. Quaternization of the benzimidazole ring of (S)-4a by

• (S)-8 in 98% yield. Amine (S)-8 was then treated with (Boc)2O in the presence of Et3N at room temperature for 24 h to give the corresponding BOC derivative (S)-4b in 87% yield. Quaternization of the benzimidazole ring of (S)-4b with methyl iodide in acetonitrile gave the corresponding benzimidazolium

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• ). This route has been used to prepare several ondansetron analogues based on different amine components. Benzimidazoles Nearly all benzimidazole containing drugs such as esomeprazole (190, Nexium), omeprazole (191, Prilosec), lansoprazole (192, Prevacid), pantoprazole (193, Protonix) and rabeprazole (194

• instance shows this in the synthesis of the benzimidazole core of pantoprazole [61]. The benzimidazole ring in rabeprazole (194, Figure 6) is only substituted at position 2 and can be easily prepared by the same procedure. In a similar strategy, the benzimidazole structure 210 in the angiotensin II

• regioselectivity of the imidazole formation. The benzimidazole ring is then assembled by treating this diamine with tetraethyl orthocarbonate under Lewis acid conditions. The synthesis is concluded by installation of the tetrazole ring and acetal side chain, the latter is cleaved under physiological conditions

Fluorometric recognition of both dihydrogen phosphate and iodide by a new flexible anthracene linked benzimidazolium-based receptor

• Kumaresh Ghosh and
• Debasis Kar

Beilstein J. Org. Chem. 2011, 7, 254–264, doi:10.3762/bjoc.7.34

• to afford the diamide 4 in 80% yield. Subsequent reaction of 4 with anthracene coupled benzimidazole 3 (prepared in 64% yield from benzimidazole and 9-chloromethylanthracene in the presence of NaH in dry THF) gave the dichloride salt 5 in 55% yield. Anion exchange using NH4PF6 in warm aqueous CH3OH

• fluorescence spectra on a Perkin-Elmer LS 55 spectrofluorometer, respectively. Synthesis of 3 [49] To a solution of benzimidazole (0.300 g, 2.54 mmol) in dry THF (15 mL), NaH (0.14 g) was added and the mixture refluxed for 1 h under a nitrogen atmosphere. The reaction mixture was then cooled to room

• purified by silica gel column chromatography with 80% ethyl acetate in petroleum ether as eluent to afford the compound 6 (0.309 g, 64% yield). The chloro-amide 6 (150 mg, 1.2 mmol) was heated under reflux in dry CH3CN (20 mL) with the anthracene-coupled benzimidazole 3 (570 mg, 1.85 mmol) for 4 days. The

Structure and reactivity in neutral organic electron donors derived from 4-dimethylaminopyridine

• Jean Garnier,
• Alan R. Kennedy,
• Leonard E. A. Berlouis,
• Andrew T. Turner and
• John A. Murphy

Beilstein J. Org. Chem. 2010, 6, No. 73, doi:10.3762/bjoc.6.73

• both the positive charge and an unpaired electron upon oxidation; this stabilization is greater than is afforded by sulfur in TTF. Benzimidazole-derived donor 6 (E11/2 = −0.82 V; E21/2 = −0.76 V vs SCE in DMF) [18][19][20], combines the stabilization of positive charge and of an unpaired electron

Synthesis of some novel hydrazono acyclic nucleoside analogues

• Mohammad N. Soltani Rad,
• Ali Khalafi-Nezhad and
• Somayeh Behrouz

Beilstein J. Org. Chem. 2010, 6, No. 49, doi:10.3762/bjoc.6.49

• derivatives were conducted according to Scheme 1. As shown in Scheme 1, condensation of imidazole, 2-phenylimidazole, hydantoin, benzimidazole and benzotriazole with 2-bromoacetophenone and 4′-methoxy-2-bromoacetophenone gave the key intermediates, ketones 1a–1g. Based on our literature survey, we recognized

• largely prevented. However, from our experience, using triethylamine (TEA) as a homogeneous base instead of K2CO3 (which was previously employed by Liu et al.) produced more satisfactory results. Hence, the reaction of imidazole or benzimidazole derivatives with 2-bromoacetophenones and TEA in the

Efficient and improved synthesis of Telmisartan

• A. Sanjeev Kumar,
• Samir Ghosh and
• G. N. Mehta

Beilstein J. Org. Chem. 2010, 6, No. 25, doi:10.3762/bjoc.6.25

• -formylphenylboronic acid 10 with 2-(2-bromophenyl)-4,4-dimethyl-2-oxazoline (11) as the key step (90% yield). The benzimidazole moiety 15 was constructed regioselectively via a reductive amination-condensation sequence, replacing the alkylation of the preformed benzimidazole step in the previously published route

• the benzimidazole derivative 3. After saponification, the free carboxyl group is condensed with N-methyl-1,2-phenylenediamine to afford the bis-benzimidazole 4, which is then alkylated with the 4′-(bromomethyl)-2-biphenylcarboxylic acid tert-butyl ester (8) to give, after hydrolysis of the ester group

• . The resulting amine 14 was not isolated but cyclized in situ to the n-propyl benzimidazole 15 in 80% yield in refluxing glacial acetic acid. Finally, cleavage of the oxazoline moiety in 15 by acid afforded Telmisartan (1) (Scheme 3). Conclusion In conclusion, a concise and selective synthesis of the

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• specifically to the minor groove of the DNA. A pentameric thymidyl DNG incorporating bis-benzimidazole (Hoechst 33258) ligand (64) was synthesised [105]. The stability of DNG-Hoechst conjugates 64 and 65 with a 30-mer double-strand DNA (dsDNA) and single-strand DNA (ssDNA) were evaluated. Fluorescent emission