Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• ligand (such as pyridine or pyrazine), valence tautomerism from ligand-centered oxidation to a metal-centered one is achieved due to the stabilization of an octahedral Ni(III). These properties allow the tweezers to reach six distinct and stable states by playing with three orthogonal stimuli that are

• : (i) metal coordination for closing/opening of the tweezers, (ii) reversible oxidation, (iii) pyrazine guest binding in the oxidized state. Such an example demonstrates the potential of the molecular tweezers architecture to go beyond simple two-level switches and access multilevel systems. Catalytic

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• ) possible. By using a similar procedure to that applied to the synthesis of compounds 4, we succeeded in the preparation of 14Н-quinoxaline[2,3-b]phenoxazine derivatives 5 (Scheme 3). The nitrogen atoms in the oxazine and pyrazine rings of 5, N(7), N(12), and N(14), offer three possible positions for the N

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• 616 nm. Based on the photophysical properties of compounds 54a and 54b, which were synthesized in the previous study (Scheme 11), it is evident that the addition of the second biphenylene-fused pyrazine group to the structure leads to a substantial red shift towards the NIR region. This observation

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• , thus indicating well-matched energy levels, and exhibited superior performance. However, Qx38, featuring a thieno[3,4-b]pyrazine acceptor and more quinoidal backbone, suffered from reduced electron injection and increased recombination rates [43]. The challenge associated with the coplanarity of Qx

• )aromatic compounds (Qx53) with a chalcogenodiazolo[3,4-b]pyrazine scaffold. These compounds exhibited narrow bandgaps (from 1.25 to 1.44 eV) and demonstrated n-type organic semiconductor properties [56]. Jin and co-workers focused on improving the charge-transfer characteristics of a semiconducting

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• , several polyhalogenated aromatics could be chemoselectively engaged at one C–X bond, even for 1-bromo-4-iodobenzene (1f). Apart from N-methylpyrrole, other substituted pyrroles, thiazine (4o), pyrazine (4p) and electron-rich benzenes (4q) were found to be suitable trapping reagents with varying efficiency

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• -triazolo[4,3-a]pyrazine scaffold [5]. This particular series, known as OSM Series 4, has demonstrated significant potency against various strains of Plasmodium falciparum (Pf) with IC50 values as low as 16 nM. The series also showed decent in vitro human liver microsome and human hepatocyte stability, with

• of an ether linker on the pyrazine ring, with a two methylene unit chain length between the heterocyclic core and benzylic substituent, improved the potency of these compounds [16]. Hence, scaffolds 1–3 were then converted into a series of ether-linked triazolopyrazines with phenethyl alcohol or

• spectrum also confirmed the presence of the phenyl ether sidechain at C-5 of the pyrazine ring, based on correlations from the aromatic protons δH 6.90 (H-20, H-24) to δC 34.3 (C-18), and δH 4.60 (H-17) to δC 135.5 (C-19) and 145.0 (C-5). This assignment was further confirmed by ROE correlations from H-17

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• technique after a synthetic transformation are highlighted in the following section (Scheme 14, Table 3). A continuous flow crystallization was performed using a trisegmented tubular crystallizer (KRAIC) coupled with a catalytic hydration of pyrazine carbonitrile [115]. After passing the reaction setup, the

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• denitrogenative reduction to quinoxaline-2-amines 17 was noticed as a side reaction. Depending on the residue in 4-position (R, Table 1) on the pyrazine ring of the tetrazolo[1,5-a]quinoxaline, the formation of either the triazole or the imidazole product or both products occurred. For groups with electron

Synthesis, optical and electrochemical properties of (D–π)₂-type and (D–π)₂Ph-type fluorescent dyes

• Kosuke Takemura,
• Kazuki Ohira,
• Taiki Higashino,
• Keiichi Imato and
• Yousuke Ooyama

Beilstein J. Org. Chem. 2022, 18, 1047–1054, doi:10.3762/bjoc.18.106

• -based photoabsorption and fluorescence bands of OTK-2 appear in a shorter wavelength region than those of the corresponding (D–π)2A-type fluorescent dye having an azine ring (pyridine, pyrazine or triazine ring) as a substitute for the phenyl ring. However, the molar extinction coefficient (εmax) and

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• . Across the years, it was employed to prepare 2-hydroxypyrazines but some of its limits, notably regioselectivity issues when starting from α-ketoaldehydes, certainly hampered a full-fledged generation of pyrazine-containing new chemical entities of potential interest in medicinal chemistry. The present

• occurrence of 3,5-substituted-2-hydroxypyrazine as the major reaction product. Keywords: α-aminoamide; condensation; hydroxypyrazine; methylglyoxal; phenylglyoxal; Introduction In a recent report [1], the many ways a pyrazine nucleus is able to interact with proteins were reviewed. In this text, it was

• also mentioned that this heterocycle appears to be under-represented in the DrugBank database (in comparison with pyridine-containing substances) plausibly because of a lesser “availability of pyrazine fragments in vendors”. For chemists, this statement could be translated as “fragments” far more

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• with the Lewis acids discussed in this review and thus lead to a significant shift of their optoelectronic properties. It has been confirmed that organic molecules containing pyrimidine, pyrazine, and indole groups display similar interactions upon the addition of Lewis acids [40][41][42]. Lewis acid

• the excited states, accounting for the decrease of band gap [27][37][43]. In 2018, Li et al. used density functional theory (DFT) to investigate the energy levels of polymers 19 (P1) and 20 (P2, Figure 10) containing pyrazine groups before and after the addition of B(C6F5)3 (see Figure 11a) [45

• ]. Considering the electrostatic potential surface (EPS) maps (see Figure 11b) of the pyrazine-containing polymers before and after B(C6F5)3 coordination, it is likely that B(C6F5)3 sacrificed the electron density of the polymer skeleton and turned it from an electron-rich to an electron-deficient species. This

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• common nitrogen-containing compounds such as pyridine, pyrazine, 1H-pyrazole, 1H-indole, 1-methyl-1H-indole, piperidine, and piperazine were subjected to screening. Pyridine and piperidine slightly hamper the reaction of 1g (Table 2, entries 2 and 7, 80–82%). Other nitrogen-containing compounds have more

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• . Kovalevskaya Str., 22, Yekaterinburg 620219, Russian Federation 10.3762/bjoc.17.2 Abstract Novel carbazole-based [6]helicenes fused with an azine ring (pyridine, pyrazine or quinoxaline) have been prepared through a five-step synthetic sequence in good overall yields. Commercially available 2,3-dihaloazines

• , we synthesized carbazole-based [6]helicenes fused with an azine ring (quinoxaline, pyrazine or pyridine ones). Scheme 2 represents the current work. We envisaged that combining the carbazole unit with the readily available azine building block would result in the formation of donor–acceptor hybrid

• data given in Table 6, it can be seen that the interplanar angle between the terminal rings A and F of the pyridine-fused [6]helicene 10c is the largest in the series (average value is 62°). The same value for [6]helicene 12 is equal to 56.7° [42]. The helicity of pyrazine-fused [6]helicene 10b and

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• pyrazine-fused trichalcogenasumanenes have been assembled via the transformation of 1,2-dibutoxybenzene unit into the corresponding ortho-quinones by means of FeCl3 in CH2Cl2/MeCN at room temperature (Scheme 44) [79][80][81]. Interestingly, it was observed that 1,2-dibutoxy groups could be selectively

• generate the corresponding pyrazine-fused sumanene networks 169a–f and 170a–f in low-to-good yields (Scheme 44). As can be inspected from Scheme 45, oxidation of 155 and 160 with both oxone (potassium peroxymonosulfate) and H2O2 afforded the one-ring-opened product 177. Interestingly, when these compounds

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• , giving selectively the C-2-substituted product in moderate to excellent yield (Scheme 27a). However, only traces of the product were detected employing benzoxazole. Six-membered heteroaromatic compounds, such as pyridine, pyrazine, quinazoline, and even carboline, in some cases fused to a benzene ring

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• mode of binding for each compound was similar to panobinostat in HDAC8 (Figure 2). Two differences were however observed in the mode of binding of TOI4. It was shown that the pyridazine ring did not lay as planar in the gorge as the pyrazine and pyrimidine rings of TOI1 and TOI2, respectively. The

• interaction with the Zn2+ ion. TOI3-rev, like that of TOI1, TOI2, and TOI4 produces two parallel-displaced π–π interactions with Phe-152 and Phe-208 (Figure 2). The pyrimidine ring of TOI3-rev also lays planar in the gorge similar to the pyrazine and pyrimidine rings of TOI1 and TOI2. The indole ring of TOI3

• inhibition results against HDAC8. Both of these inhibitors have pyrimidine rings in the core; thus, the data suggests that while this ring structure did produce inhibition, it was not as effective as the inclusion of a pyrazine ring. This finding is consistent with our computational data which demonstrated

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

• ]. Switchable mechanically interlocked molecules (MIM) that rely on multivalency have been studied rarely, thus Chen et al. have reported the design and highly efficacious synthesis of a novel two-component, triply interlocked [2](3)catenane C–H3·6PF6 19 (Figure 16) by use of a pyrazine-extended triptycene

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

• the formation of hydrogen bonds, an approach known as ‘crystal engineering’ (see, for instance, [13][14] and references therein). Indeed, whereas several two-component molecular systems cocrystallizing in a special layered way involving pyrazine, quinoline and phenazine as the H-bond acceptor and

Synthesis, photophysical and electrochemical properties of pyridine, pyrazine and triazine-based (D–π–)₂A fluorescent dyes

• Keiichi Imato,
• Toshiaki Enoki,
• Koji Uenaka and
• Yousuke Ooyama

Beilstein J. Org. Chem. 2019, 15, 1712–1721, doi:10.3762/bjoc.15.167

• and OUJ-2 with two (diphenylamino)carbazole thiophene units as D (electron-donating group)–π (π-conjugated bridge) moiety and a pyridine, pyrazine or triazine ring as electron-withdrawing group (electron-accepting group, A) have been designed and synthesized. The photophysical and electrochemical

• lowering of the LUMO energy level are dependent on the electron-withdrawing ability of the azine ring, which increases in the order of OUY-2 < OUK-2 < OUJ-2. Keywords: D–π–A structure; fluorescent dyes; pyrazine; pyridine; triazine; Introduction Donor–π-conjugated–acceptor (D–π–A) dyes are constructed of

• an electron-donating group (D) such as a diphenyl or dialkylamino group and an electron-withdrawing group (electron-accepting group, A) such as a nitro, cyano, and carboxy group or an azine ring such as pyridine, pyrazine and triazine linked by π-conjugated bridges such as oligoenes and heterocycles

Selective detection of DABCO using a supramolecular interconversion as fluorescence reporter

• Indrajit Paul,
• Debabrata Samanta,
• Sudhakar Gaikwad and
• Michael Schmittel

Beilstein J. Org. Chem. 2019, 15, 1371–1378, doi:10.3762/bjoc.15.137

• fluorescence at λ = 602 nm. Ligands, such as pyrazine, 2-chloropyrazine, 1,4-dimethylpiperazine, anthracene, pyrene, coronene, perylene, and perylene-3,4,9,10-tetracarboxylic dianhydride were compared to DABCO. Only in presence of DABCO the fluorescence maximum was shifted to λ = 618 nm along with the color

• repulsion. For instance, pyrazine creates notable repulsive interactions of the α-H towards the zinc porphyrin ring in a sandwich complex. Apparently, stability gains through π–π stacking in the sandwich with pyrene, coronene, etc. are not strong enough to compensate for the strain in [Cu2(1)(2)(guest)]2

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• ; Introduction Pyrazine and piperazine ring systems are key structural elements in a large number of biologically active molecules [1][2][3][4][5][6]. Compounds containing these scaffolds were shown to behave as anticancer agents [2][3][4][5], sodium channel blockers [5], and also display antiviral activity [7

• the nucleophilic addition of Grignard reagents to N-acylpyrazinium salts. A literature search showed this organometallic reagent reacting with pyrazine N-oxides towards the one-pot synthesis of N-Boc-protected N-hydroxy-substituted piperazines in good yields [6]. Methylmagnesium iodide was observed

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• -hydroxy-4,5-benzotropone (238): Some quinoxaline and pyrazine derivatives 254–256 were synthesized from 1,2-phenylenediamine (251), 1,2-diaminocyclohexane (252), and ethylenediamine (253) with 4,5-benzotropolone 238 (Figure 11) [162]. Compound 256 can be converted to methylated 257. Tarbell’s group also

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• ] activity. There are several methods reported in literature for the construction of pyrazolo[3,4-b]pyrazine nucleus. Quiroga et al. [144] studied the reaction of o-aminonitrosopyrazoles 227 and cyclic β-diketones 58 in various solvents like pyridine, acetic acid and N,N-dimethylformamide for the synthesis

• pyridine to give 1,3,6-trisubstitutedpyrazolo[3,4-b]pyrazine-5-carbonitriles 230 in good yields. 5-Carbonitrilepyrazolo[3,4-b]pyrazines 230 were hydrolyzed to corresponding pyrazolo[3,4-b]pyrazine-5-carboxylic acids 231 and subsequently converted to acid chloride 232 at reflux temperature with thionyl

• ]pyrazines 230 which was used as synthetic precursor to generate several other substituted pyrazolo[3,4-b]pyrazine derivatives via amidoxime and carbohydrazide

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• to proceed depending on the structure of the substrate and the nucleophile. The first, Beirut reaction [1][2][3][4][5][6][7][8][9][10], allowing to transform the furoxan ring to pyrazine or imidazole N-oxides as well as N-hydroxyimidazole occurs under the action of α-unsubstituted aldehydes, ketones

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• imidazo[1,5-a]pyrazine structure show inhibitory activity against kinases BTK [1], MEK [2], ACK1 [3], mTORC1(2) [4], c-Src [5], growth factor IGF-1R [6] and act as the antagonists of Hedgehog pathway dependent malignancies [7]. Imidazo[1,5-a]pyrimidines are inhibitors of the bone morphogenic protein [8