¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• spectroscopy. For monocyclic derivatives of azoles, the structures of N-alkylated regioisomers can be determined using 2D H-(C)-N multiple bond correlation (HCNMBC) experiments [22][23] using natural isotopic abundance. These experiments rely on the magnetization transfer through 13C-15N J-coupling constants

• tetrazolo[1,5-b][1,2,4]triazin-7-one in TFA solution. The formation of an adamantyl cation and NH-tetrazolo-triazine during the isomerization reaction was confirmed. (A) Adamantylated azoles and derivatives of 1,2,4-triazolo[5,1-c][1,2,4]triazine with antiviral activities. (B) Four sites sensitive to N

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• the nucleobases are usually protected with acyl groups and the 5´-OH of the monomeric building block with a 4,4’-dimethoxytrityl group (DMTr), or sometimes with its monomethoxytrityl analog (MMTr) [4][5]. To achieve coupling, phosphoramidites are activated with azoles [6], such as tetrazole [7], its

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• crystalline compounds, ligands for asymmetric synthesis, and they are also convenient reagents in organic synthesis [1]. Although bicyclic assemblies of azoles exhibit interesting chemical properties and biological activities [1][7][8][9][10][11] isoxazoles conjugated to other azole rings are poorly presented

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• -translationally modified into the final product, and a heterotrimeric complex that is responsible for both heterocyclisation of serine and cysteine residues, and subsequent oxidation of (ox/thi)azolines into (ox/thi)azoles (Figure 3A). This catalytic complex consists of “C” and “D” proteins (annotated as McbB and

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

• heteroaryls, Schreiber and Wang [54] attempted and achieved the Cu(OAc)2-catalyzed C–H amidation/sulfonamidation of azoles 29 and polyfluorinated arenes 30 under the assistance of pyridine (Py) as ligand and base. Corresponding products 31, 32 and 33 were readily acquired with fair to excellent yield

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

• Sciences, Beijing, 100190, P. R. China 10.3762/bjoc.11.233 Abstract A copper-catalyzed oxidative direct formation of amides from nonactivated carboxylic acids and azoles with dioxygen as an activating reagent is reported. The azole amides were produced in good to excellent yields with a broad substrate

• scope. The mechanistic studies reveal that oxygen plays an essential role in the success of the amidation reactions with copper peroxycarboxylate as the key intermediate. Transamidation occurs smoothly between azole amide and a variety of amines. Keywords: amidation; azoles; Cu-catalyzed; molecular

• key intermediate to make the subsequent amide formation feasible (Scheme 1b). In our work, azoles have been chosen as the amines due to their special bioactivity [31]. To the best of our knowledge, Cu salt has not yet been used for catalyzed, oxidative direct amide formation. We report the first

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• ). The catalytic iodination of electron deficient 1,3-azoles was recently realized by Zhao et al. Under the catalytic conditions consisting of LiOt-Bu, 1,10-phenanthroline and CuBr2, a class of different conventional azoles 17, including benzoxazoles, benzothiazole, N-methylbenzimidazole, 5-phenyloxazole

• -catalyzed arene C–H fluorination of benzamides. Copper-catalyzed arene C–H iodination of 1,3-azoles. Copper-catalyzed C–H halogenations of phenols. Proposed mechanism for the C–H halogenation of phenols. Copper-catalyzed halogenation of electron enriched arenes. Copper-catalyzed C–H bromination of arenes

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• pyrrole and indole substrates 1 and 2, the unsubstituted azoles were reacted with aryl and heteroaryl iodides under copper catalysis. As far as the derivatives 1a,b, 1d,e and 2a–e are concerned, the reactions were carried out by using 1.5 equiv of the azole, 0.2 equiv of copper, 2 equiv of caesium

• )phenyl)-substituted azoles were isolated in high yields (Scheme 1). In a previous study [33], we have shown that hexane containing N,N,N’,N’-tetramethylethylenediamine (TMEDA) is a suitable solvent to perform the C2 deproto-metallation with the TMP-based lithium–zinc as the base of commercially available

• various attempts to deprotonate bromobenzene using the lithium–zinc base failed, a result probably due to degradation of the deproto-metallated compound through benzyne formation [46], it proved possible to accumulate at room temperature the arylmetal compounds formed from the N-(4-bromophenyl)azoles 1e

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

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

• lead to loss of vision. Candida albicans is one of the most widespread fungal pathogens involved in fungal keratitis [1][2]. The most common antifungal treatments include the use of polyenes and azoles; however, a significant treatment failure rate exists with these pharmacological agents [3

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• catalyst instead of copper since palladium has been widely recognized as powerful transition metal catalyst involved in C2-arylations of azoles [25][33][46][47][55][56][57][58]. C2-Arylation of 1-(indol-3-yl)-N-PG-THIQs 4 was expected to be challenging since the C3 position of the indole is blocked by the

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

• possible to determine the barrier to proton transfer of benzimidazole itself in HMPA-d18, thus providing a missing value in heterocyclic tautomerism of azoles and benzazoles [33]. Experimental Four of the compounds reported in this paper are commercial (Sigma-Aldrich): 1, 2, 3 and 5. We reported the

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• the products. Therefore, there is a need for the development of a new, simple synthetic route, applicable to a wide range of C-nitro-NH-azoles. Since 1998 when Chan and Lam [21][22] described a novel method for the formation of C–N bonds through the copper-catalyzed coupling of NH-containing

• was also investigated. For this purpose the cross coupling of phenylboronic acid with a series of C-nitro-NH-azoles such as: 3(5)-nitropyrazole (1a) (pKa = 9.81) [46], 4-nitropyrazole (1b) (pKa = 9.67) [46], 4(5)-nitroimidazole (1c) (pKa = 8.93) [47], 3-nitro-1,2,4-triazole (1d) (pKa = 6.05) [48] and

• presented in this paper make this route more valuable. Conclusion In conclusion, we have developed an efficient and simple method for the cross coupling of arylboronic acids with C-nitro-NH-azoles in the presence of a catalytic amount of simple copper salts. The reaction takes place in a protic solvent

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• Pawel Borowiecki Malgorzata Milner-Krawczyk Jan Plenkiewicz Warsaw University of Technology, Faculty of Chemistry, Noakowskiego St. 3, 00-664 Warsaw, Poland 10.3762/bjoc.9.56 Abstract Racemic 1-(β-hydroxypropyl)azoles were prepared by solvent-free direct regioselective ring opening of 1,2

• using enzyme-catalyzed kinetic resolution of 1-(β-hydroxypropyl)azoles as a key step. We have shown that this attempt is simple and allows the preparation of new types of optically active ionic liquids. Inhibitory activity of the newly synthesized CILs was tested towards gram-negative and gram-positive

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• fully substituted 1,2,3-triazoles with excellent chemo- and regioselectivities. Likewise, the optimized catalytic system proved applicable to the direct preparation of 1,2-diarylated azoles through a one-pot C–H/N–H arylation reaction. Keywords: cascade reaction; C–H functionalization; copper

• - and step-economical access to annulated carbo- as well as O- and N-heterocycles. Finally, we found that the catalytic system also proved to be applicable to the one-pot copper-catalyzed direct arylation of various azoles 5 through N–H/C–H bond cleavages with aryl iodides 6 as the organic electrophiles

• regioselective fashion, and also allowed for twofold C–H/N–H bond arylations on various azoles. Experimental General information Catalytic reactions were carried out under an inert atmosphere of nitrogen using predried glassware. All chemicals were used as received without further purification unless otherwise

Synthesis of oleophilic electron-rich phenylhydrazines

• Aleksandra Jankowiak and
• Piotr Kaszyński

Beilstein J. Org. Chem. 2012, 8, 275–282, doi:10.3762/bjoc.8.29

• : arylhydrazines; methodology; synthesis; Introduction Mono-arylhydrazines I are important intermediates in the synthesis of a number of heterocycles, including indoles [1] and some azoles (for example [2][3]), many of which exhibit biological activity and are used in drug development [4][5][6]. Arylhydrazines

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

• -A system featuring ICT. Two principal orientations of the imidazole-derived charge-transfer chromophores. Donor–acceptor triaryl push–pull azoles 4a–h [31][32]. Y-shaped CT chromophores with an extended π-conjugated pathway and various donor and acceptor substitution patterns [16][33][34][35

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• methodology The first examples of direct C–H heteroarylation of various azoles were reported by Ohta, including the direct C5-selective pyrazinylation of oxazole with chloropyrazines in the presence of Pd(PPh3)4 as catalyst and potassium acetate base (Scheme 4) [36][37]. This protocol was successfully applied

• , which was highly effective in the direct arylation of oxazoles with various arylbromides (Scheme 7) [44]. In his initial study, Miura observed a substantial amount of C2-arylation of azoles, including benzoxazole, using Cu(I) alone as catalyst (Scheme 8) [40]. In 2007, this methodology was judiciously

• arylation of heterocycles, including electron-rich azoles with aryl bromides, by using potassium phosphate as a base and phenanthroline as a ligand (Scheme 8) [47]. Over the past few decades, it has also been demonstrated that copper catalysis is not required in order to attain good yield and selectivity in

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• azoles are a class of synthetic compounds that possess one or more azole rings. Whilst both imidazole and triazole are five membered ring heterocycles, imidazole contains two ring nitrogen atoms, whereas triazoles have three. However, compared with imidazoles (clotrimazole, ketoconazole, miconazole

• to some synthetic antifungal agents makes it necessary to continue the search for new antimicrobial substances. Azoles are the largest class of antifungal agents in current clinical use [36]. During the last two decades, the incidence of invasive fungal infections (IFIs) increased dramatically

• invasive Aspergillus and Candida infections. It has a wide range of antifungal activity against various fungal strains such as Candida spp. resistant to older azoles, Cryptococcus neoformans, Aspergillus spp., Rhizopus spp, Bacillus dermatitidis, Candida immitis, Histoplasma capsulatum and other

Michael-type addition of azoles of broad-scale acidity to methyl acrylate

• Sławomir Boncel,
• Kinga Saletra,
• Barbara Hefczyc and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2011, 7, 173–178, doi:10.3762/bjoc.7.24

• , no corresponding regioisomers were obtained. Keywords: imidazole derivatives; methyl acrylate; Michael-type addition; pyrazole derivatives; 1,2,4-triazole derivatives; Introduction Derivatives of azoles are important biologically active compounds. Many, especially those containing imidazole

• of various azoles to α,β-unsaturated carbonyl and nitro derivatives has been frequently exploited in the synthesis of precursors of biologically active compounds [3][7][8][9][10][11][12][13][14][15]. This reaction, although structurally restricted to α,β-unsaturated carbonyl compounds and their

• reports on the synthesis of Michael-type adducts of azoles by the use of microwave irradiation [7][24]. The optimisation of aza-Michael reactions with N-methylimidazole as the base catalyst was published in 2007 by Liu et al [25]. However, when this catalyst was used with azoles of narrower-scale acidity

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

• has led to an ongoing search for safe and efficient chemotherapeutic agents with potent broad-spectrum antifungal activities. Some of the best known antifungal azole drugs having rational versatility in structures are miconazole (A), oxiconazole (B) and related compounds, namely aryl azoles (Figure 1

• different strategies were considered for the synthesis of the title compounds taking into account the differences in chemical behavior of purine and pyrimidine nucleobases compared to azoles. Because of their better solubility, reactivity and ease of separation of products, the reactions of the azole

• that among published methods for N-alkylation of imidazole derivatives [26][27][28][29][30][31][32][33][34], the method developed by Liu et al. [35] was the most appropriate one for N-alkylation of azoles and their derivatives, since in this method the formation of quaternary imidazolium salts is

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• immunosuppressed patients, especially those suffering from AIDS or cancer, fungal infections have become a significant, often life-threatening problem [1][2]. Present treatments rely on antifungals such as polyene antibiotics (amphotericin B), nucleoside analogs (5-fluorocytosine) and azoles (fluoconazole