Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• °C) in the presence or absence of bases (Et3N). Keywords: deep eutectic solvents; imidazoles; phenacyl azides; phenacyl halides; pyrimidines; Introduction In a world with dwindling petroleum resources, the setting up of more and more sustainable routes for the preparation of heterocyclic compounds

• place smoothly using such neoteric solvents (Scheme 1, path a) [16]. Among nitrogen-containing heterocyles, imidazoles and pyrimidines are important structural scaffolds commonly found in natural products [17][18], light-emitting devices [19][20], and pharmacologically active compounds as anticancer

• chloride (1b) with NaN3 (1.5 equiv) in ChCl/Gly at 80 °C gave the best results, as it provided the adducts 3a/3a' in an overall 88% yield after 12 h reaction time (Table 1, entries 1–4). Of note, imidazoles 3a/3a' were found to precipitate directly from the aforementioned eutectic mixture during the

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• . Conclusion An environmentally benign NDL catalyst was characterized and utilized as a heterogeneous catalyst for the synthesis of 2-aryl-1-arylmethyl-1H-benzo[d]imidazoles, dihydropyrimidinones/ -thiones, and 2-amino-4-(hetero)aryl-3,5-dicarbonitrile-6-sulfanylpyridines in a mixture of ethanol and H2O 1:1

• conditions.a Effect of the catalyst loading.a Effect of the temperature.a NDL-catalyzed synthesis of 2-aryl-1-arylmethyl-1H-benzo[d]imidazoles 3.a NDL-catalyzed synthesis of dihydropyrimidinone/-thione derivatives 7.a NDL-catalyzed synthesis of 2-amino-4-(hetero)aryl-3,5-dicarbonitrile-6-sulfanylpyridines 11.a

• Green chemistry metrics for the synthesis of 2-aryl-1-arylmethyl-1H-benzo[d]imidazoles 3. Green chemistry metrics for the synthesis of dihydropyrimidinones/-thiones 7. Green chemistry metrics for the synthesis of 2-amino-4-(hetero)aryl-3,5-dicarbonitrile-6-sulfanylpyridines 11. Supporting Information

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• deprotection then furnished 83b in reasonable yields between 68 and 87%. Bis(diphenylphosphine)-substituted imidazoles were also synthesized by Karthik et al. [87] starting from the diiodoimidazole derivative 84. The lithium chloride mediated magnesium/iodine exchange reaction of 84 followed by the addition of

Reversible switching of arylazopyrazole within a metal–organic cage

• Anton I. Hanopolskyi,
• Soumen De,
• Michał J. Białek,
• Yael Diskin-Posner,
• Liat Avram,
• Moran Feller and
• Rafal Klajn

Beilstein J. Org. Chem. 2019, 15, 2398–2407, doi:10.3762/bjoc.15.232

• imidazoles are denoted by black arrows. Color codes: C, gray; N, blue; Pd, orange. Hydrogens, counterions, and solvent molecules are not shown for clarity. UV–vis absorption spectrum of an aqueous solution of (E-1)22 (blue) and following exposure of this solution to UV light for 5 min (orange). Inset: Ten

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• imidazoles [8][9], polypyrroles [10][11], and indole moieties [12][13], as part of supramolecular receptors, triazole heterocycles containing macrocycles have recently been introduced as new host molecules for the selective recognition of ions, mechanically interlocked molecules (MIMs), supramolecular

1,2,3,4-Tetrahydro-1,4,5,8-tetraazaanthracene revisited: properties and structural evidence of aromaticity loss

• Arnault Heynderickx,
• Sébastien Nénon,
• Olivier Siri,
• Vladimir Lokshin and
• Vladimir Khodorkovsky

Beilstein J. Org. Chem. 2019, 15, 2059–2068, doi:10.3762/bjoc.15.203

• hydroquinones or chloranilic acid as the H-bond donors (the O–H···N=C H-bonds) are known [15][16], the examples of the N–H···N=C bonds are less numerous and involve mostly aminopyrimidines and imidazoles [13][14]. Derivatives of 3 can be of special interest as flexible supramolecular synthons [14][17] owing to

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• could be easily prepared according to a previously reported general method [17]. The N-arylation of benzo[d]imidazoles with 1-bromo-2-fluorobenzene derivatives in the presence of K3PO4 (5 equiv) at 150 °C gave 1a–i in 45–99% yields. All synthetic details including the preparation method for 1-(2

• residue was purified by silica gel chromatography (n-hexane/AcOEt). (a) Ortep drawing of 2a (50% probability, only one of two independent molecules is shown) and (b) packing structure. The component based solvent was omitted for clarity. Cs2CO3-mediated cyclization of 1-(2-bromoaryl)imidazoles with Se

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• –Crafts reaction; triflic acid; Introduction Imidazoles and benzimidazoles are important heterocyclic scaffolds in pharmaceuticals and agrochemicals [1][2][3][4][5][6][7][8][9][10]. They also have applications in the fields of dyes, chemo-sensing, and fluorescent materials [3]. (Benz)imidazoles are a

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