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

• 3 and 2-aminopyridine (28), azole amide 3 was mixed with 2-aminopyridine (28) under the standard conditions. Surprisingly, the azole amide 3 was transformed into 29 in 92% yield, which clearly demonstrated that transamidation occurred in this process (Scheme 4). Further exploration into a variety of

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

• the bis-heterocycles 1b and 2b, better results were obtained by doubling the amount of base (using 1 equiv of ZnCl2·TMEDA and 3 equiv of LiTMP). Under the reaction conditions employed above, the deprotonation occurred on the pyridine ring, at the 2 position adjacent to the azole substituent. The

• identified by X-ray diffraction (Figure 3, left, see Supporting Information File 2). It is known that anisole can be ortho-deprotonated using the lithium–zinc base in THF [35]. It was thus of interest to involve N-(4-methoxyphenyl)-substituted azole substrates in the deprotonation–iodination sequence. Under

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

Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

• Anastasia S. Kostyuchenko,
• Vyacheslav L.Yurpalov,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2014, 10, 1596–1602, doi:10.3762/bjoc.10.165

• azole–thiophene bonds [14][16][17]. However, the best results (higher yields, more facile purification, shorter reaction times) are obtained by the formation of the azole ring via appropriately functionalized bithiophenes [14][22]. Recently, we have developed a new method for the preparation of 3-alkyl

• account of its energy, to a π–π* transition. The wavelength maximum of this band clearly changes with the azole unit, as well as with the thiophene solubilising substituent, from 365 nm for 18, 376 nm for 13, 395 nm for 14 up to 406 nm for 15. The difference of 19 nm between the two 1,3,4-oxadiazole

• reconstruction takes place upon their optical excitation, the dominant reason being the bond order switching accompanying the benzenoid–quinoid transition. Small differences in the magnitude of this shift are observed arranging in a sequence 15 > 18 > 13 ≈ 14, and scaling well with the atomic radii of the azole

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 presence of the nitro group (a strong electron-withdrawing substituent) in the azole entails the adjustment of the conditions of N-arylation reaction. Besides a very recently published approach involving N-arylation of nitroazoles with diaryliodonium salts [20], already described methods utilize

• ]. It involves several steps: transmetallation of boronic acid with a catalyst, coordination of the azole molecule to the Cu(II) species followed by oxidation of copper(II) into copper(III) in the presence of oxygen, and then reductive elimination releasing the product and Cu(I) complex. A regeneration

• product. A series of experiments, when either an excess of azole or a base over other reagents was used, resulted in decreased yields. Nevertheless, the base should be used in stoichiometric proportion to the azole. Both increasing and decreasing the proportion led to lower yield of the product. With an

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

• stereoselectivity (E = 6). The racemic acetyl esters (±)-4a and (±)-4b used for determination of the enantiomeric configurations were prepared in good isolated yields by lipase-catalyzed esterification of the appropriate 1-(β-hydroxypropyl)azole (±)-3a or (±)-3b with vinyl acetate as the acyl donor (Scheme 1). The

• diastereomeric esters prepared from the separated enantiomers of the alcohols (+)-5a or (+)-5b and (R)- and (S)-enantiomers of methoxyphenylacetic acid (MPA, Mosher reagent) (Scheme 2). The utility of this method applied to secondary alcohols possessing heterocyclic azole rings has been demonstrated by us

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• investigated are cruzain [7][8][9][10], the major cysteine protease active in the parasite, and T. cruzi CYP51 (TcCYP51), a 14-α-demethylase enzyme of the cytochrome P450 family required for ergosterol biosynthesis [11][12][13][14]. TcCYP51 is analogous to the fungal enzyme targeted by the azole class of

Theoretical study on β-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole

• Adrian Fifere,
• Narcisa Marangoci,
• Stelian Maier,
• Adina Coroaba,
• Dan Maftei and
• Mariana Pinteala

Beilstein J. Org. Chem. 2012, 8, 2191–2201, doi:10.3762/bjoc.8.247

• secondary hydroxyl rims. The results have revealed that the most stable complex is formed when the azole residue of the propiconazole enters the cavity of the cyclodextrin through the narrow hydroxyl’s rim. Keywords: β-cyclodextrin; inclusion complexes; PM3; propiconazole; Introduction The occurrence of

• with azole-containing medicines has led to fungal resistance to this class of compounds, especially in the case of HIV patients with repeated recurrent episodes [1][2]. Today, the number of reported cases of clinic resistance to antifungal drugs is growing and mycologists have warned about an

• thermodynamically favored, and that the complex is stabilized in the B orientation, which has a stabilization energy about ~20 kJ smaller as compared to the A configuration (Table 1). These facts are in good agreement with those exposed in Figure 2, confirming a higher probability of azole ring inclusion into the β

Fluorescent hexaaryl- and hexa-heteroaryl[3]radialenes: Synthesis, structures, and properties

• Antonio Avellaneda,
• Courtney A. Hollis,
• Xin He and
• Christopher J. Sumby

Beilstein J. Org. Chem. 2012, 8, 71–80, doi:10.3762/bjoc.8.7

• electron rich azole rings and methyl substituents make it particularly hard to reduce. Its first reduction potential is −1.21 V and its second was not observed as it occurs outside the solvent window for dichloromethane. Most hexaaryl[3]radialenes are orange or red in colour with UV–visible absorption

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)2 and A-π-IM-(π-D)2 push–pull systems. An initial effort to synthesize and apply azole derivatives as CT chromophores and to study their optical (non)linearities can be ascribed to Moylan, Miller, and co-workers as early as 1993 [31][32]. Donor–acceptor-substituted imidazoles, oxazoles, and

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

• arylation of azoles were recently reported by the groups of Greaney and Tan [73][74]. Greaney selected the oxazole-4-carboxylate esters and 4-carboxyoxa(thia)zoles as substrates to prepare the naturally occurring 2,4-linked bis(azole). Interestingly, poly(azole) structures are also prepared by repeating the

• decarboxylative direct C–H cross-coupling sequence with the residual ester group (Scheme 25a) [73]. Mechanistically, a Cu(II)-catalyzed decarboxylation reaction produces the C4-cuprated azole, which intercepts the arylpalladium acetate complex produced by prior palladation of the substrate at the C2-position, to

• -free, Pd(II)-based catalyst for direct decarboxylative cross-coupling of azole with various benzoic acids (Scheme 26a). In particular, benzoxazole was successfully coupled with 2,6-dimethoxybenzoic acid in 45% yield. Thus, without the assistance of a strong base, a carbopalladation was proposed as a

Synthesis and oxidation of some azole-containing thioethers

• Andrei S. Potapov,
• Nina P. Chernova,
• Vladimir D. Ogorodnikov,
• Tatiana V. Petrenko and
• Andrei I. Khlebnikov

Beilstein J. Org. Chem. 2011, 7, 1526–1532, doi:10.3762/bjoc.7.179

• . Selenium dioxide-catalyzed oxidation of benzotriazole thioether by H2O2, however, proceeds selectively and yields sulfoxide only. Keywords: azole; oxidation; sulfone; sulfoxide; thioether; Introduction Compounds comprising two pyrazole moieties linked by an aliphatic spacer act as bidentate chelating

• dismutase-like activity of copper(II) complexes with bis(pyrazole) ligands [5][6]. Copper(II) complexes with azole-derived thioether ligands were proposed as models for type I copper proteins [7]. The sulfur atom in a thioether spacer gives an additional possibility for modification of the ligand structure

• here was 89%, and no formation of the mercapto-derivative was detected. The properties of azole-containing thioether can be varied by functionalization of the azole ring or oxidation of the sulfur atom, and therefore we have studied the reactivity of thioethers 3–5 in electrophilic substitution and

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

• agents posaconazole (12) and ravuconazole (13)) are synthetic compounds that have one or more azole rings with three nitrogen atoms in a five membered ring. They act by inhibition of the cytochrome P450-dependent conversion of lanosterol to ergosterol [42]. Triazoles act as cytochrome P450 14α

• -demethylase inhibitors. This enzyme is involved in the conversion of lanosterol to ergosterol which is helpful in the cell wall synthesis. In this mechanism the basic nitrogen of the azole ring is tightly bound to the heme iron of the fungal cytochrome P450 preventing substrate and oxygen binding. Inhibition

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

• , Department of Chemical Organic Technology and Petrochemistry, Krzywoustego 4, 44-100 Gliwice, Poland, tel.: +48 32 237 10 32, fax: +48 32 237 10 32 10.3762/bjoc.7.24 Abstract An optimisation of Michael-type addition of azole derivatives of broad-scale acidity – ranging from 5.20 to 15.00 pKa units – namely

• protocol and a simple work-up. In the Michael-type additions of azole N–H acids, numerous catalysts such as KF/Al2O3 [8], CeCl3∙7 H2O/NaI [9], NaH or ZnCl2 [10], K2CO3 [11], anhydrous K3PO4 [12], (NH4)2Ce(NO3)6 (CAN) [22] or ionic liquids, e.g., Cu(acac)2 immobilised in [bmim][BF4] [15] have been used

• -centred organic bases expressed by the equation: pKa (DMF) = 0.9463 pKa (water) + 1.4154 [32][33]. This semi-empirical relationship enables an initial selection of a base required for a sufficient level of deprotonation of N–H azole acids. 1a and 1b as weak N–H acids required an equimolar amount of a

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

• Abstract The syntheses of novel hydrazono acyclic nucleosides similar to miconazole scaffolds are described. In this series of acyclic nucleosides, pyrimidine as well as purine and other azole derivatives replaced the imidazole function in miconazole and the ether group was replaced with a hydrazone moiety

• 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

• ], hereby, we wish to report the synthesis of some novel hydrazono acyclic nucleosides having similar scaffolds to the miconazole framework. In these compounds, the nucleobases including pyrimidines, purines and other azole derivatives were substituted as heterocyclic cores and the ether bond in miconazole