Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• imidazoles 2 from tertiary propargylamides and ammonium chloride under conventional heating [3]. More recently, we applied the Beller protocol to the synthesis of 2-substituted 5-methyloxazoles 3 from secondary propargylamides [4]. Being curious to explore more variants of N-carbonyl propargylamines, we

• preparation of ureas 4 could, in principle, enable a three-component entry to imidazoles 5 (an attractive option from the standpoint of library array synthesis), we compared the isolated yield of the above reaction (with the ready-made urea 4a) with the yield obtained in the three-component format. To our

• synthesis of trisubstituted 2-aminoimidazoles. This is the first example illustrating the utility of such ureas in the synthesis of imidazoles as previously reported syntheses only involved base-promoted cyclization into 2-imidazolones. The reaction can be conveniently conducted in a three-component format

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• -arylpropanoic acids. The interaction of 2-amino-4-arylimidazoles with aromatic aldehydes or isatins and acyclic methylene active compounds has led to the formation of pyrrolo[1,2-c]imidazole-6-carbonitriles, pyrrolo[1,2-с]imidazole-6-carboxylates and spiro[indoline-3,7'-pyrrolo[1,2-c]imidazoles], which can be

• with isatins and aliphatic CH acids stable Michael adducts have not been fixed. Cyclocondensation has readily led to the formation of 6'-substituted 3',5'-diamino-1-alkyl-2-oxo-1'-arylspiro[indolin-3,7'-pyrrolo[1,2-c]imidazoles], which can be considered as the analogues of alkaloids with both pyrrolo

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• products has been reviewed [15][16] and this review will focus only on IMCRs. Consecutive IMCRs Synthesis of small-ring heterocycles (tetrazoles, ketopiperazines, imidazoles, imidazolines and thiazoles) The use of consecutive Ugi reactions in the synthesis of heterocycles was first described in 2001 by Ugi

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• to heterocycles, for instance the Radziszewski reaction to imidazoles [61][62]. As an example, the condensation of 1,2-diketones DK with o-phenylenediamine to quinoxalines QU [63] employing cerium ammonium nitrate [64] as catalyst was investigated (Scheme 29). This transformation proceeded smoothly

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• -heterocycles, N-oxides 1 cannot be prepared via oxidation of the parent imidazoles by treatment with an oxidizing agent, e.g., with a percarboxylic acid [6]. Imidazole N-oxides are versatile substrates for the preparation of diverse imidazole derivatives and the most characteristic feature is their 1,3-dipolar

• completed after 2 h, and the main product isolated in 39% yield was the expected 1-(adamantyloxy)imidazole 8a (Scheme 4). In the product, the diagnostic HC(2) signal in the 1H NMR spectrum shifts high-field and appears at 7.34 ppm. Analogously, deoxygenation of N-oxides 7b–d led to the required imidazoles

• adamantylations of some benzimidazoles and imidazoles have already been reported [31], similar reactions with heterocyclic N-oxides have not been published yet. For that reason, in the final part of the study, a preliminary experiment aimed at the O-adamantylation of imidazole N-oxide 7a was carried out under

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• nucleophilic reagents. This feature enables one to carry out the direct nucleophilic functionalization of the C(sp2)–H bond, thus leading to novel C(5)-modified 2H-imidazoles. We have established that carboranyllithium, generated in situ from 1,2-dicarba-closo-dodecaborane [66], can be involved in the above

• considered as nucleophilic substitution of hydrogen (SNH) in non-aromatic N-oxides of 2H-imidazoles 1a–d. It has also been shown that the SNH reactions can be realized via either an "addition–elimination" SNH(AE) mechanism, or through an "addition–oxidation" SNH(AO) scheme to form imidazolyl carbonanes 4a–d

• 1a–d. The second step can be carried out in both eliminative and oxidative versions, the structure of the final carboranylated 2H-imidazoles 4a–d and 5a–d being controlled by the reaction conditions used. In order to accomplish the nucleophilic substitution of hydrogen according to the "addition

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

• to both the electronics of the arene and the nucleophilicity of the amine. Particularly electron-rich arenes such as N-methylindole are not tolerated, as is the case for relatively nucleophilic amines such as imidazoles, anilines or alkylamines. The reported substrates are particularly valuable to

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• major isomer (Scheme 10). Compound 18 is a valuable intermediate for a variety of coupling reactions to yield 1,5-disubstituted imidazoles – structural motifs which are generally difficult to obtain – in a selective fashion. The proposed reaction mechanism based on DFT calculations starts with the

• triarylamines 17 through a double arylation of anilines. Selective conversion of novel aryl(imidazolyl)iodonium salts 1b to 1,5-disubstituted imidazoles 18. Selected examples for the application of cyclic diaryliodonium salts 19. Tandem oxidation–arylation sequence with (dicarboxyiodo)benzenes 20. Oxidative α

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• , comprising phenylthio [56], 5-chloro-8-quinolyl [57], morpholidate [48] and imidazolide moieties [58][59]. Imidazole activation in DMF with ZnCl2 was first reported by Sekine et al. [60] and is the most often used method for the formation of triphosphates. P-Imidazoles are known to react with numerous

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• ]BF4) and water [66]. The substrate scope was investigated on 11 imidazothiazoles, 13 imidazo[1,2-a]pyridines and 6 imidazoles (Scheme 43). The reaction was simple, achieved at room temperature and had a good tolerance for various functional groups. However, for the trifluoromethylation of imidazoles

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• environmental reasons. These issues also led to the quest for biodegradable MOFs, the first being prepared in 2010 by Miller et al. [77]. Another family of MOFs, ZIFs (zeolitic imidazolate frameworks), that involves organic imidazoles as linkers, has been explored for medicinal purposes as a result of the

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• of imides with alkyl halogenides, and the results are presented in this paper. Until now, ball milling N-alkylations of ureas [15], hydrazones [16], imines [17][18], pyridines [19], pyrimidines [20], imidazoles [21], secondary amines [22], as well as allylic alkylation reactions [23] were reported in

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

• ]. Encouraged by these results a variety of functionalized N-heterocycles were oxidatively dehydrogenated with IBX, to afford their aromatic counterpart. For example imidazoles 11, dihydroisoquinoline 12, pyridine 13, and pyrrole 14 were obtained from their corresponding heterocyclic precursors 7–10 in

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

• effective electrophilic activating agent for the formation of the bisimine and promotes the subsequent steps (intramolecular nucleophilic attack and the following 1,3-hydride shift), finally affording the 1,2-disubstituted imidazoles (b). In contrast, path ii is a non-catalyzed reaction. In path ii, when

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• closer look at these results suggested that the nucleophilic behavior of DBU highly depends on specific substrates. Vaidyanathan and co-workers reported the DBU-catalyzed addition of amines to acyl imidazoles [16], however, using a stoichiometric amount of DBU, Rajagopal et al. observed nucleophile

Solvent-free synthesis of novel para-menthane-3,8-diol ester derivatives from citronellal using a polymer-supported scandium triflate catalyst

• Lubabalo Mafu,
• Ben Zeelie and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 2046–2054, doi:10.3762/bjoc.12.193

• [6], acyl imidazoles or acyl ureas [7]. Acylation of alcohols in particular, provides a cheap and effective method for the synthesis of esters with potential applications in pharmaceutical products such as fragrances, flavours, surfactants or solvents [8][9]. Generally, these reactions are done in

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• protonation or quaternization of neutral precursors (imidazoles, amines, phosphines, pyridine or sulfides) with Brønsted acids or haloalkanes/dialkylsulfates, respectively. In the next step, a variety of ionic liquids are obtainable by anion exchange, either through direct treatments with Lewis acids or by

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• catalyst (Scheme 15). The use of an acidic additive also allowed the synthesis of fused bicyclic imidazoles through a GII-catalyzed RCM reaction (Scheme 16) [53]. Only few examples of RCM involving dienes that contain N-heteroaromatics were described on non-protonated species. In 2001, in the course of

• moieties such as pyridines, pyrimidines, imidazoles and pyrazoles (Scheme 37). From the selected examples discussed above, we tried to delineate some trends regarding to the use of alkenes possessing N-heteroaromatics in RCM and CM. In RCM, GI and GII are usually preferred and diluted conditions are

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

• of o-halobenzamides 82 and (benzo)imidazoles 87 for the one-pot synthesis of (benzo)imidazoquinazolinones 88 under the catalysis of CuI and assistance of L-proline. A subsequent oxidation using molecular oxygen was required for the final formation of products. According to the results, the mechanism

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• . The N-(2-keto)amide skeleton is of particular interest, as it serves as a synthetic precursor for various small heterocyclic compounds such as imidazoles, oxazoles and thiazoles [7][8][9]. Azirine, the smallest nitrogen-containing unsaturated three-membered heterocyclic system, is well known as a

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• -imidazoles based on the formation of a pyrrole ring via the reaction of 2H-azirines with 1-alkyl-3-phenacyl-1H-imidazolium bromides [29], in which one example of the synthesis of ethyl 4-imidazolylpyrrole-2-carboxylate from ethyl 3-methyl-2H-azirine-2-carboxylate was described. Earlier it was found that

• hydrolyzing the ester group. Ylides 2 can also be debenzylated, affording the corresponding pyrrolyl imidazoles 12. Thus, ylide 2h was debenzylated on Pd/C with hydrogen to produce methyl 5-(4-fluorophenyl)-4-(1H-imidazol-1-yl)-3-phenyl-1H-pyrrole-2-carboxylate (12d) in quantitive yield. As mentioned above

Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

• Anxo Fernández-Ferreiro,
• Noelia Fernández Bargiela,
• María Santiago Varela,
• Maria Gil Martínez,
• Maria Pardo,
• Antonio Piñeiro Ces,
• José Blanco Méndez,
• Miguel González Barcia,
• Maria Jesus Lamas and
• Francisco.J. Otero-Espinar

Beilstein J. Org. Chem. 2014, 10, 2903–2911, doi:10.3762/bjoc.10.308

• ]. Specifically, azole-based medications, which include imidazoles (e.g., miconazole, clotrimazole, and ketoconazole) and triazoles (e.g., fluconazole, itraconazole, posaconazole, and voriconazole), inhibit ergosterol synthesis in the cell wall [4]. Fluconazole is considered to be a good therapeutic option for

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• Leuven (KU Leuven), Celestijnenlaan 200F, B-3001 Leuven, Belgium 10.3762/bjoc.10.145 Abstract A microwave-assisted synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles from a phenylazide, propargyloxybenzaldehyde and a 1,2-diaminobenzene is proposed. Keywords

• effective than the sum of their individual components. The therapeutic application of 2-(3-fluoro-phenyl)-1-[1-(substituted-phenyl)-1H-[1,2,3]-triazol-4-yl-methyl)-1H-benzo[d]imidazoles has been demonstrated by treating tuberculosis[19]. However, there has been little progress in the development of such

• first, followed by the formation of triazole by CuAAC reaction to give the desired product 4a. Conclusion We developed a novel microwave-assisted, Cu(I)-catalyzed, three-component reaction for the synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles in good to

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• electron-rich and electron-poor anilines are suitable partners for these reactions, whereas alkylamines and benzylamine gave worse results. Moreover, the third partner (Nu in Scheme 19) is limited to one substrate as in the reaction employing diethyl phosphite (32). Indoles 30 and imidazoles 31 can bear