Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• pyridine as an additive (Scheme 6) [46]. Similarly, benzothiazoles also efficiently underwent hydroheteroarylation by using suitable ligands [47]. The reaction was successfully extended to indoles and benzimidazoles 7 bearing a removable 2-pyrimidyl (2-pym) directing group with alkynes at ambient

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• , benzothiophenes and benzimidazoles seen in many drugs. In another demonstration of the value of diazonium salts, the König group have published a protocol for the synthesis of substituted benzothiophenes using Eosin Y photocatalysis, starting from o-methylthioarenediazonium salts and substituted alkynes (Scheme

• benzofused heterocycles (indole etc.) – such as benzimidazoles or tetrazolopyridines are often seen in medicinal chemistry. Singh et al. reported a method for preparing 3-arylnitrobenzimidazoles from 2-aminopyridines and nitroalkanes, using green LED Eosin Y photocatalysis, with molecular oxygen as the

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• on the phenyl ring where the two benzimidazoles were linked via an oxygen atom. Most of these conjugates showed significant antitumor activity in vitro compared to Hoechst 33258. Amongst them, conjugate 49 (Figure 10) was found to be most potent with IC50 values of 0.56 μM for HL60 (Human

• modeling study. In general, bisbenzimidazole derivatives (conjugate 57) exhibit much better antibacterial activity than mono-benzimidazoles for Gram-positive strains. More importantly, the linker lengths and composition have dramatic influence on DNA binding and cell uptake, suggesting that the roles of

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• bromination of the α-carbon using CBrCl3 as the Br source. This in situ halogenation strategy has been employed for the synthesis of quinoxalines [23], oxazoles [24][25], pyrido[1,2-a]benzimidazoles [26], imidazo[1,2-a]pyridines [27][28][29][30], thiazoles [31][32] and benzothiazoles [33][34]. With weak

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• 1,3-N,N-dinucleophile, leading to tetrahydropyrimido[1,2-a]benzimidazoles 3 (Scheme 4) [38]. In continuation of our studies on the synthesis of azolo-annelated heterocycles we herein report the results of our investigations on the reactions between N-arylitaconimides and 1,2-diamino-4-phenylimidazole

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• , benzimidazoles, pyrimidines, indoles, etc. [114][136][137][138][139]. Further improvements are in demand for the development of synthesis with solvent-less, time efficient, less byproducts, energy saving, easy handling procedures, etc. [112][140][141]. In 2016, Rousseau and co-workers reported a solvent-free

• ]. Jang and co-workers reported a mechanochemical synthesis of benzimidazoles [143][144], benzoxazole [145] and benzothiazole derivatives in presence of ZnO nano particles as catalyst [146]. Using 0.5 mol % of ZnO nano particles which were grown on aromatic imine D as capping agent, resulted in the best

• with methanol. Secondly, the method was also applicable up to 10 g of 2-aminothiophenol and avoided the use of toxic metals which are common in benzimidazole synthesis [147][148]. Subsequently, the same group reported the preparation of 1,2-disubstituted benzimidazoles via mechanochemical activation

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• pharmaceutical intermediates [3][4][5][6]. Substituted benzimidazoles occur in veterinary medicines, as anthelmintic agents and are used in a plethora of human therapeutic areas such as psychiatrics, ulcers, hypertension, cancers etc. [7][8][9][10]. Quinazolines and quinazolones are obtained in bioactive

• ≈0.6 equivalents of oxone as an appropriate oxidant in wet dimethylformamide, at room temperature for the reaction of o-phenylenediamine 31 with appropriate aldehydes to afford 2-substituted benzimidazoles 32 in excellent yield [42]. The reaction conditions are amenable to a wide range of substrates

• benzimidazoles 33a, involved a one-pot condensation–ring distortion–oxidative dehydrogenation of o-aminobenzylamines 33 and appropriate aldehydes [43]. The reaction conditions included 0.6 equiv of oxone at room temperature with DMF as the solvent. Various aliphatic, aromatic and heteroaromatic aldehydes are

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• developed for guided photodynamic therapy [3]. On the other hand, various heterocycles also find multiple medical applications: bis(benzimidazoles), bis(benzoxazoles) and benzothiazoles display anticancer activities [4], 2-arylbenzothiazole is a privileged scaffold in drug discovey, and the main areas of

• via acetylene bridge [9]. All these compounds were synthesized from the corresponding aldehydes already possessing an heteroaromatic moiety. The development of the catalytic approaches opened an easy access to 2-aryl-substituted benzothiazoles, benzoxazoles and benzimidazoles. Kumada–Tamao–Corriu [10

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• -benzylthiazolo[3,2-a]benzimidazoles 6 in good yields (Scheme 2a) [81]. In a closely related investigation, Shafiee and co-workers also found that the cyclocondensation of 2-amino-N-propargylbenzamides 7 with CS2 in a KOH/EtOH system gave the corresponding 2-methylenethiazolo[2,3-b]quinazolinones 8 in good to

• thiazole-2-thiones 3 through the thermal cyclocondensation of N-propargylamines 1 with carbon disulfide as developed by Batty and Weedon [75]. (a) One-pot synthesis of 2-benzylthiazolo[3,2-a]benzimidazoles 6 through a base-catalyzed cascade reaction of internal N-propargylamines 4 and CS2. (b) Synthesis of

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• -mediated hydroxylation of (2-pyridyl)arenes. Removable pyridine moiety directed hydroxylation of arenes. Removable quinoline moiety directed hydroxylation of arenes. CuCl2 catalyzed hydroxylation of benzimidazoles and benzoxazoles. Disulfide-directed C–H hydroxylation. Pd(OAc)2-catalyzed hydroxylation of

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• that afforded isocyanates 52. These were in turn treated in situ with catalyst 44 to afford the final products 50 via presumed iminophosphorane intermediates 53. Subsequently this research group used a very similar strategy for the synthesis of polysubstituted benzimidazoles 54 via sequential Ugi and

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• showed that benzimidazoles, Biginelli adducts, dihydropyridines, furans, pyrans, pyridinones, and thiophenes had a high representation of intrinsic greenness; whereas, a high proportion of MCRs producing chromene-4-ones, coumarins, indoles, and pyrazoles had low probabilities of achieving intrinsic

Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

• Natividad Herrera Cano,
• Jorge G. Uranga,
• Mónica Nardi,
• Antonio Procopio,
• Daniel A. Wunderlin and
• Ana N. Santiago

Beilstein J. Org. Chem. 2016, 12, 2410–2419, doi:10.3762/bjoc.12.235

• ][7] or benzothiazole [8][9] rings in numerous compounds is an important structural element for their biological and medical applications. For example benzimidazoles are widely spread in antiulcer, antihypertensive, antiviral, antifungal, anticancer, and antihistaminic medicines, among others [10][11

• -disubstituted benzimidazoles (b). Therefore, the main drawbacks of current protocols for the synthesis of benzimidazoles include the use of expensive reagents, difficulties in the preparation of the catalyst, long reaction times, a narrow scope of substrates, tedious work-up procedures, the use of hazardous

• solvents, which are not environmentally friendly. Thereby, we propose the use of Er(OTf)3 as catalyst to provide an eco-friendly, economical and easy to work-up procedure for the synthesis of 1,2-disubstituted benzimidazoles, which can be afforded in only two minutes. In order to selectively obtain 2

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• acid type. They have been widely used for several synthetically useful transformations like dehydration of amides leading to nitriles [23][24] or the Beckmann rearrangement [23][25]. They have also been employed in the synthesis of heterocycles such as benzimidazoles, benzothiazoles, benzoxazoles [23

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• were disclosed by Wang et al. [80]. The synthesis using 92 and benzimidazoles 87 provided benzimidazole-fused cyclic sulfonamides 93. The reaction allowed the synthesis of various products with fair to high yields with the assistance of L-proline as ligand. The expected conversion took place also in

Molecular-oxygen-promoted Cu-catalyzed oxidative direct amidation of nonactivated carboxylic acids with azoles

• Wen Ding,
• Shaoyu Mai and
• Qiuling Song

Beilstein J. Org. Chem. 2015, 11, 2158–2165, doi:10.3762/bjoc.11.233

• into the desired 3 via intermediate D along with the recycling of the Cu catalyst. Conclusion In conclusion, Cu-catalyzed oxidative direct amidation from nonactivated carboxylic acid with benzimidazoles under dioxygen atmosphere with molecular oxygen as an activating reagent has been described. Azole

• , the use of oxygen as both the sole terminal oxidant and activating reagent, and inexpensive and readily available starting materials. This is the first Cu-catalyzed, direct, amide formation between nonactivated carboxylic acids and benzimidazoles in coupling reagent, traditional activating, reagent

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• -substituents, where one of the N-substituent is an aromatic or a benzylic group and the other substituent an alkyl [25][26][27][28][29][30] or benzyl [31][32] group. A synthetic strategy for the preparation of sterically demanding monoaryl benzimidazolium salts starts from the corresponding benzimidazoles

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• studied for the construction of heterocycles. We have reported on a highly efficient gold/silver-catalyzed intramolecular hydroamination of terminal alkynes in water for the synthesis of fused tricyclic xanthenes [34]. On the basis of this methodology, we have also afforded two fused benzimidazoles

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• -substituted benzimidazoles with ethyl bromoacetate and electron-deficient alkynes, in 1,2-epoxybutane, gave a variety of pyrrolo[1,2-a]quinoxalin-4-ones and pyrrolo[1,2-a]benzimidazoles. The influence of experimental conditions on the course of reaction was investigated. A novel synthetic pathway starting

• from benzimidazoles unsubstituted at the five membered ring, alkyl bromoacetates and non-symmetrical electron-deficient alkynes in the molar ratio of 1:2:1, in 1,2-epoxybutane at reflux temperature, led directly to pyrrolo[1,2-a]quinoxalin-4-ones in fair yield by an one-pot three-component reaction

• ][9][10][11][12][13]. The development of more efficient synthetic methods towards these compounds is an active research area [14][15][16]. Recently, we reported on the formation of pyrrolo[1,2-a]benzimidazoles along with pyrrolo[1,2-a]quinoxalines in the one-pot three-component reaction of 1

An experimental and theoretical NMR study of NH-benzimidazoles in solution and in the solid state: proton transfer and tautomerism

• Carla I. Nieto,
• Pilar Cabildo,
• M. Ángeles García,
• Rosa M. Claramunt,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2014, 10, 1620–1629, doi:10.3762/bjoc.10.168

• .10.168 Abstract This paper reports the 1H, 13C and 15N NMR experimental study of five benzimidazoles in solution and in the solid state (13C and 15N CPMAS NMR) as well as the theoretically calculated (GIAO/DFT) chemical shifts. We have assigned unambiguously the "tautomeric positions" (C3a/C7a, C4/C7 and

• C5/C6) of NH-benzimidazoles that, in some solvents and in the solid state, appear different (blocked tautomerism). In the case of 1H-benzimidazole itself we have measured the prototropic rate in HMPA-d18. Keywords: CPMAS; DNMR; GIAO; proton transfer; tautomerism; Introduction Of almost any class of

• heterocycles it can be said that they have relevant biological and medicinal chemistry properties, because, for instance, over 80% of top small molecule drugs by US retail sales in 2010 contain at least one heterocyclic fragment in their structures [1]. Benzimidazoles besides being the skeleton of many

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• , [18F]FPM-IMPY, has shown less promising results. This compound, in which one of the N-methyl groups of IMPY was replaced with a [18F]fluoropropyl moiety, showed lower binding affinity than IMPY and poor pharmacokinetics [96]. Benzimidazoles The benzimidazole scaffold is highly similar to the

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• -dihydrofurans, polysubstituted pyridines, pyrido[1,2-a]benzimidazoles and charge-separated zwitterionic salts [26][27][28][29][30][31]. We envisaged that in situ generated pyridinium ylide might react with the reactive carbonyl group of isatins to afford spiro epoxyoxindoles (Scheme 1). To test this feasibility

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

• least not excessively electron poor, aromatic aldehydes, application of this transformation early in the synthesis ultimately proved successful. Although this route is not suitable for large-scale production of 1, multigram quantities of this compound and benzimidazoles of comparable complexity are

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

• ammonia, amines, hydrazines and phenolates to give 2-nitroaniline, 2-nitrophenylhydrazine and diphenyl ether derivatives. Reduction of the nitro group of 4-tribromomethylsulfonyl-2-nitroaniline yielded the corresponding o-phenylenediamine substrate for preparation of structurally varied benzimidazoles

• molecules remained to be synthesized: Phenylhydrazones and benzimidazoles. The acid-catalyzed reaction of phenylhydrazine derivative 7b with aldehydes or ketones (Scheme 5) afforded a series of phenylhydrazones possessing various substituents (Table 2; see Supporting Information File 1 for further details

• on products 8a–8l). The two-step synthesis of benzimidazoles featured aniline derivative 7a as the starting material (Scheme 6). The first transformation, i.e., the reduction of the nitro group, was initially intended to be completed with stannous chloride in concentrated hydrochloric acid as a

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

• diimidazoles, benzimidazoles, bis(benzimidazoles), imidazole-4,5-dicarbonitriles, and imidazole-derived chromophores chemically bound to a polymer chain. Keywords: charge transfer; chromophore; conjugation; donor–acceptor system; imidazole; Introduction Over the past three decades, great progress has been

• −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

• of NH proton abstraction by using a fluoride anion. Remarkably large differences between the β values of protonated/deprotonated forms showed that benzimidazoles are potent molecules for a new type of NLO molecular switching. Chromophores featuring a 4,5-dicyanoimidazole acceptor moiety Since the