Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• ; Introduction Pyrrole has a great range of applications in organic synthesis because of its occurrence in many active natural products, synthetic pharmaceuticals, and optoelectronic materials [1][2]. The pyrazinones derived from the pyrazine ring by single oxidation of one carbon atom also show very important

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

• patterns. It is well known that they can undergo a number of cyclization reactions to produce various N-heterocycles and complex natural products. In this context we recently reviewed their role in the syntheses of pyrrole [65], pyridine [66], quinoline [67], pyrazine [68], 1,4-oxazepane, and 1,4-diazepane

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

• dihydropyridine, hydantoin, imidazole, indole, isoquinoline, isoxazole, oxazole, 4H-pyran, pyrazine, pyridazine, pyridine, pyridinone, pyrimidine, pyrimidone, pyrrole, 3H-quinazolin-4-one, quinoline, 1H-quinolin-4-one, and thiophene. For heterocycles that are composed of a fused aromatic ring, such as

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• conditions allowed smooth oxidation providing the target compound in an excellent yield. For the regioisomeric diazine, (4-chlorobenzyl)pyrazine (5d), no oxidation was observed after 24 h at 100 °C. To our delight, by increasing the reaction temperature to 130 °C, (4-chlorophenyl)(pyrazin-2-yl)methanone (6d

• , entries 4 and 5). This interesting selectivity was further expanded on 6-(4-methylbenzyl)-2-methylpyrazine (18a). Pyrazine 18a features three possible positions for methylene oxidation: a benzyl, benzhydryl and a 1,4-diazinylmethyl moiety. When 18a was submitted to the Cu-catalyzed reaction conditions at

• 130 °C, only the bis-oxidation product 6-(4-methylbenzoyl)pyrazine-2-carbaldehyde (20a) was obtained in 61% (Table 5, entry 1). Interestingly, when switching to FeCl2·4H2O as the catalyst in the reaction, only mono-oxidation at the benzhydrylic methylene occurred, providing (6-methylpyrazin-2-yl)(p

Synthesis and characterization of the cyanobenzene-ethylenedithio-TTF donor

• Sandrina Oliveira,
• Dulce Belo,
• Isabel C. Santos,
• Sandra Rabaça and
• Manuel Almeida

Beilstein J. Org. Chem. 2015, 11, 951–956, doi:10.3762/bjoc.11.106

• pyrazine groups substituted TTFs recently reported by our group [13][22][23]. Conclusion In conclusion, we have prepared in fair yield a new non-symmetrically substituted cyanobenzene TTF-type electron donor, CNB-EDT-TTF, by a cross coupling reaction followed by chromatographic separation. The crystal

Interactions between tetrathiafulvalene units in dimeric structures – the influence of cyclic cores

• Huixin Jiang,
• Virginia Mazzanti,
• Christian R. Parker,
• Søren Lindbæk Broman,
• Jens Heide Wallberg,
• Karol Lušpai,
• Adam Brincko,
• Henrik G. Kjaergaard,
• Anders Kadziola,
• Peter Rapta,
• Ole Hammerich and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2015, 11, 930–948, doi:10.3762/bjoc.11.104

• central benzene or pyrazine ring [4]. If the two TTFs are oxidized at the same potentials in an electrochemical experiment, they behave instead as electrochemically independent redox centres with only weak Coulombic interactions between the cations. Interactions can also be tracked spectroscopically, and

• lock the molecule into a conformation where the two TTF units are in co-planarity [22]. The communication dramatically increases when the two TTFs are fused together as in compound 21 [23] or to either a pyrazine or benzene ring [4]. Thus, compounds 21–23 all show four distinguishable one-electron

• close together by a single bridge does not by itself seem to increase significantly the electronic communication when stepwise oxidations are used as a measure hereof. Instead, fusing directly together the two TTF units, connecting them to a benzene or pyrazine ring, or even to a larger radiaannulene

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• Würzburg, Germany 10.3762/bjoc.10.288 Abstract Nanodiamonds functionalized with different organic moieties carrying terminal amino groups have been synthesized. These include conjugates generated by Diels–Alder reactions of ortho-quinodimethanes formed in situ from pyrazine and 5,6-dihydrocyclobuta[d

• wet-chemical quantification method in cases where other techniques like elemental analysis fail due to unfavourable combustion behaviour of the analyte or other impediments. Keywords: amino groups; carbon nanomaterials; Diels–Alder reaction; Kaiser test; nanodiamond; pyrazine; Introduction Surface

• depicted in Scheme 1. Besides the novel functionalization methods using pyrazines and cyclobutenes (see below) several nanodiamond conjugates were prepared for comparison similar to already reported procedures. It is known that pyrazine derivatives react with fullerenes in a cycloaddition reaction [13

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• 10.3762/bjoc.10.74 Abstract 3-Aryl-2H-azirines react with acylketenes, generated by thermolysis of 5-arylfuran-2,3-diones, to give bridged 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene-2,10-diones and/or ortho-fused 6,6a,12,12a-tetrahydrobis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine-4,10-diones. The latter

• routes of bis[1,3]oxazino[3,2-a:3′,2′-d]pyrazine skeleton formation revealed a new domino reaction of 3-aryl-2H-azirines occurring in the presence of furandiones: acid-catalyzed dimerization to dihydropyrazine followed by consecutive cycloaddition of the latter to two molecules of acylketenes. Keywords

• [41][43][46]. It was found that water [37], Brønsted [44][48] and Lewis acids [40][41][43] facilitate the formation of pyrazine derivatives. 2H-Azirines undergo ring opening on electronic excitation to give nitrile ylides [50]. Nitrile ylide formation under thermal conditions even from such strained

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• Abstract Here we describe the use of a new open-source software package and a Raspberry Pi® computer for the simultaneous control of multiple flow chemistry devices and its application to a machine-assisted, multi-step flow preparation of pyrazine-2-carboxamide – a component of Rifater®, used in the

• pyrazine 2 to piperazine 1 (Figure 2b). Both of these steps involve flowing through heterogeneous catalysts, a metal oxide for the hydration of the nitrile and a supported precious metal for the hydrogenation of the heteroaromatic ring. Furthermore, both steps involve the addition of a volatile small

• –Ponndorf–Verley reductions [22] and Oppenauer oxidations [23] where zirconia activation is required). In fact, it seems that the extent of hydration of pyrazine-2-carbonitrile is proportional to the initial water content of the zirconium catalyst. To confirm this hypothesis, we ran a control experiment in

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• in a poor yield by application of the Skraup synthesis to 5-acetylamidoquinoxaline [16]. Notably, 7,8-diaminoquinoline dihydrochloride condensed with glyoxal bisulfite only with the amino group in position 7 and the pyrazine ring was not closed [17]. In the present case, the cyclocondensation of

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• readily obtained through well-established condensation chemistries. In the next sections the most common syntheses of a number of drugs containing the pyrimidine as well as pyridazine and pyrazine scaffolds are presented. Furthermore, some non-aromatic derivatives including bicyclic analogues of these

Cyclization of substitued 2-(2-fluorophenylazo)azines to azino[1,2-c]benzo[d][1,2,4]triazinium derivatives

• Aleksandra Jankowiak,
• Emilia Obijalska and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2013, 9, 1873–1880, doi:10.3762/bjoc.9.219

• with increasing number of fluorine atoms at the benzene ring. No triazinium ions were obtained from azo derivatives of 4-cyanopyridine, pyrazine and pyrimidine, presumably due to their instability under the reaction conditions. The experimental results and mechanism are discussed with the aid of DFT

• reactivity of the azines, and CH2OH to provide a potential synthetic handle for the incorporation into more complex structures. Here we present the synthesis of four substituted derivatives of 1a and investigate the preparation of cations derived from pyrazine 2 and pyrimidine 3 shown in Figure 2. Our

• the pyrazine derivative 5-Z (ΔG298 = 2.7 kcal/mol), which also has the lowest TS energy (ΔG‡298 = 18.7 kcal/mol, Table 2). On the other hand, the cyclization of pyrimidine 6-Z is most endergonic and has the highest TS energy among all azoazines considered in this work. These significant differences

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• electronically deficient pyridyl residue was also converted into 5e (80%) while pyrrolidine 4f bearing a pyrazine core underwent aromatization with high efficiency to give 5f (97%). The C2-symmetric scaffold 4g was efficiently converted into 5g (86%) and similar treatment of pyrimidine 4h provided pyrrole 5h in

• heteroaryl substituents, with yields ranging from 64–87%. Oxidation under the same conditions was found to be more troublesome with pyrazine 5f since alcohol 9f was isolated in only 20% yield. Similar treatment of pyrazine 5g and pyrimidine 5h gave a complex mixture of products. While the oxidation of the

4-Pyridylnitrene and 2-pyrazinylcarbene

• Curt Wentrup,
• Ales Reisinger and
• David Kvaskoff

Beilstein J. Org. Chem. 2013, 9, 754–760, doi:10.3762/bjoc.9.85

• ]pyrazine (24). FVT of 4-azidopyridine (18) as well as of 24 or 2-(5-tetrazolyl)pyrazine (23) affords the products expected from the nitrene, i.e., 4,4’-azopyridine and 2- and 3-cyanopyrroles. Matrix photolyses of both 18 and 24 result in ring expansion of 4-pyridylnitrene/2-pyrazinylcarbene to 1,5

• and Discussion Here, we report details of the FVT as well as matrix photolysis reactions of 4-azidopyridine (18) and the isomeric triazolo[1,5-a]pyrazine (24) and its precursor, 2-(5-tetrazolyl)pyrazine (23). Furthermore, we report evidence for ring expansion as well as ring opening of 4

• literature method [21]. 1,2,3-Triazolo[1,5-a]pyrazine (24) was prepared according to a literature procedure [16]. FVT of 4-azidopyridine (18) The azide (0.50 g) was distilled into the FVT apparatus from a sample flask held at 35 °C and thermolysed at 400 °C/10−2–10−3 mbar in the course of 1 h. 4,4

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

• Mohammad Piltan,
• Loghman Moradi,
• Golaleh Abasi and
• Seyed Amir Zarei

Beilstein J. Org. Chem. 2013, 9, 510–515, doi:10.3762/bjoc.9.55

• -diaminobenzene, dialkyl acetylenedicarboxylates, and ethyl bromopyruvate forms pyrrolo[1,2-a]quinoxaline derivatives in good yields. Ethylenediamine also reacts under similar conditions to produce new pyrrolo[1,2-a]pyrazine derivatives. Keywords: acetylenedicarboxylates; benzene-1,2-diamine; ethyl bromopyruvate

• ; pyrrolo[1,2-a]pyrazine; pyrrolo[1,2-a]quinoxaline; Introduction Among the various classes of heterocyclic compounds, quinoxalines, a class of N-containing heterocycles, form an important component of many pharmacologically active compounds [1][2][3][4]. For example, the quinoxaline ring is a constituent

• research area. The syntheses of pyrrolo[1,2- a]isoquinolines have previously been reported by us [28]. In this paper, we describe a simple synthesis of functionalized pyrrolo[1,2-a]quinoxaline and pyrrolo[1,2-a]pyrazine derivatives in the absence of catalysts. Results and Discussion The reaction of 1,2

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• possess interesting biological activity, the scope of the amination was investigated in somewhat more detail. Regarding the scope of the amine and coumarinyl acetate coupling reaction, dialkyl (5a–c) and the cyclic amines pyrrolidine (5d–5f), pyrazine (5g), and morpholine (5h) were competent coupling

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

• electrodes to facilitate the electron or hole injection and transfer in OLED devices. 2,5-Bis(benzimidazol-2-yl)pyrazine derivatives 70 (BBIP), with improved solubility through N,N’-dialkylation, exhibited high fluorescence intensity even in protic solvents, as well as interesting solvatochromic properties

One-pot three-component synthesis of quinoxaline and phenazine ring systems using Fischer carbene complexes

• Priyabrata Roy and
• Binay Krishna Ghorai

Beilstein J. Org. Chem. 2010, 6, No. 52, doi:10.3762/bjoc.6.52

• the synthesis of quinoxaline and phenazine ring systems has been investigated. This involves the generation of furo[3,4-b]pyrazine and furo[3,4-b]quinoxaline as transient intermediates, which were trapped with Diels–Alder dienophiles. This is the first report on furo[3,4-b]pyrazine intermediates

• ] with 2-alkynyl-3-pyrazine carbonyl derivatives, followed by the generation of a hitherto unknown intermediate e.g. furo[3,4-b]pyrazine 4 and trapping of the latter with dienophiles. Phenazine derivatives can be synthesized using similar methodology from the coupling of 2-alkynyl-3-quinoxaline carbonyl

• -phenylmaleimide (~ 1:1:1 ratio) in refluxing THF was initially investigated (Table 1, entry 1). This reaction led to a mixture of oxanorbornene derivative 7a and quinoxaline derivative 5a through the tandem generation and trapping of the furo[3,4-b]pyrazine intermediate 4 (R1 = Ph). Ring opening followed by

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32