Tuning of tetrathiafulvalene properties: versatile synthesis of N-arylated monopyrrolotetrathiafulvalenes via Ullmann-type coupling reactions

• Vladimir A. Azov,
• Diana Janott,
• Dirk Schlüter and
• Matthias Zeller

Beilstein J. Org. Chem. 2015, 11, 860–868, doi:10.3762/bjoc.11.96

• the second to the dication. Non-substituted derivative 4c shows a lower first oxidation potential than its alkylS-substituted counterpart 4a,b, as expected due to the electron-withdrawing effect of the two thioalkyl groups [28][29]. The strong electron-withdrawing effect of the 4-nitrophenyl group in

• ; CV (vs SCE, CH2Cl2): E1/2ox1 = 0.48 V, E1/2ox2 = 0.83 V. 2-[4,5-Bis(propylthio)-1,3-dithiol-2-ylidene]-5-(4-nitrophenyl)-5H-1,3-dithiolo[4,5-c]pyrrole (4d). Prepared from 7a (0.055 g, 0.140 mmol), CuI (0.014 g, 0.070 mmol), K3PO4 (0.089 g, 0.42 mmol), trans-diaminocyclohexane (7.5 µL, 0.062 mmol) and

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• ) (see Figure 1). Protein concentrations were checked by UV (λ = 280 nm). Lipase activity test [53]. Lipase activity was determined by measuring the hydrolysis of p-nitrophenyl palmitate (pNPP; Sigma). Solution A (10 mM p-nitrophenyl palmitate in 10 mL ethanol) and solution B (100 mg gummi arabicum in 90

Matsuda–Heck reaction with arenediazonium tosylates in water

• Ksenia V. Kutonova,
• Marina E. Trusova,
• Andrey V. Stankevich,
• Pavel S. Postnikov and
• Victor D. Filimonov

Beilstein J. Org. Chem. 2015, 11, 358–362, doi:10.3762/bjoc.11.41

• a rotary evaporator under reduced pressure and the crude product was purified by flash chromatography. 3-Chloropropyl (E)-3-(4-nitrophenyl)acrylate (3ba): Yield 90%, 0.90 mmol, pale yellow solid, mp 86 °C; 1H NMR (300 MHz, DMSO-d6) δ 8.23 (d, J = 8.7 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.77 (d, J

• = 16.2 Hz, 1H), 6.84 (d, J = 16.2 Hz, 1H), 4.28 (t, 2H), 3.76 (t, 2H), 2.11 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 165.6, 148.0, 142.4, 140.4, 129.5, 123.9, 122.2, 61.4, 41.9, 31.1; EI–MS m/z: 269 [M]+; HRMS m/z: calcd for C12H12NO4Cl, 269.0449; found, 269.0452. 3-Chloropropyl (E)-3-(3-nitrophenyl)acrylate

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• , oxazine 4g and adduct 7g are stable on silica and were isolated in a pure form. The reaction of azirine 1g containing a 4-nitrophenyl substituent on C3 produces only oxazine 4h and [4.3.1] adduct 7h, which were isolated in 58 and 13% yields, respectively (Table 1, entry 9). Compounds 6–8 were

• depends on the electronic effects of the para substituents in the aryl group of 3-aryl-2H-azirine 1. The [3.2.1] adduct is preferably formed from azirines 1e,f with electron-donating substituents (Table 1, entries 7 and 8), while 3-(4-nitrophenyl)-2H-azirine (1g) provides the [4.3.1] adduct only (Table 1

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

• César A. Estévez,
• José Ramón Isasi,
• Eneko Larrañeta and
• Itziar Vélaz

Beilstein J. Org. Chem. 2014, 10, 3127–3135, doi:10.3762/bjoc.10.330

• ), hydrochloric acid (37%, Panreac, Spain), dibasic sodium phosphate and monobasic potassium phosphate (99% purity, Panreac, Spain). In order to determine the activity of the β-D-galactosidase (lactase), 2-nitrophenyl-galactopyranoside (ONPG) (Sigma-Aldrich, ≥98% purity, 301.3 g/mol) was used as a substrate to

• expressed in lactase units per milliliter of solution (ALU/mL). The official monograph USP 37 assay, used to determine lactase activity of preparations derived from Aspergillus oryzae, is based on hydrolysis of the substrate o-nitrophenyl β-D-galactopyranoside (ONPG) at 37 °C and pH 4.5 (buffer prepared

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• tris(thiourea) derivative, could result. With phenyl isothiocyanate and its 4-nitro derivative, however, 3-hydrazinyl-1H-1,2,4-triazole-5(4H)-thiones 10a,b were obtained as major products in 57 and 68% yield, respectively (Scheme 5). In the case of (4-nitrophenyl) isothiocyanate, the bis(arylthiourea

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

• -withdrawing group such as 4-nitrophenyl afforded a poor yield of 7% (6e, Table 2, entry 4). The sterically demanding 1-naphthyl group furnished product 6f in unsatisfactory 14% yield. Using phenylboronic acid the yield was the same no matter whether Boc or Cbz were used as protecting group (Table 2, entries 1

• from oxidation of the corresponding THIQ. An ester functionality was well tolerated, furnishing 63% of product 7m (Table 4, entry 6) and also 4-fluorophenyl and 3-nitrophenyl groups did not hamper the reaction (Table 4, entries 4 and 5). Arylation of the nitrogen of the THIQ core was not observed in

• performed well, furnishing the desired product 7d in 65% yield (Table 5, entry 4). In case of the 4-nitrophenyl group as in 5e, which reflects a −M/−I-substituent, no conversion was observed under standard indolation conditions (5 mol % Cu(NO3)2·3H2O, 1.3 equiv t-BHP, 50 °C, 15 h). Hence, another batch (1.3

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• treatment with BF3·OEt2 of the persilylated precursor failed and inevitably led to the anhydro derivative 12. Moreover, whereas treatment with TFA/THF/H2O 90:5:2.5 of 4-nitrophenyl per-O-TBS-α-D-Araf afforded 16, 4-nitrophenyl per-O-TBS-β-D-galactofuranoside did not lead to compound 15 under the same

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• imine (Schiff base), which was subsequently reduced to PEG-g-chitosan with sodium cyanoborohydride [55], allowing retention of net charge. PEGylation can also be accomplished by condensation of the free amino groups with activated PEGs, such as PEG-NHS or PEG-p-nitrophenyl carbonate, converting the

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• ), 6.81 (d, J = 5.0 Hz, 1H), 1.97 (s, 3H). 4-Methyl-2-(2-nitrophenyl)thiophene (2b): After column chromatography (pentane/diethyl ether 95:5), a mixture of products 2a and 2b was obtained in 60% (0.131 g) yield. 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 6.91 (s, 1H), 2.19 (s, 3H). 2a was also

First synthesis of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2014, 10, 808–813, doi:10.3762/bjoc.10.76

• Dileep Kumar Singh Mahendra Nath Department of Chemistry, University of Delhi, Delhi 110 007, India 10.3762/bjoc.10.76 Abstract A synthetic protocol for the construction of new meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins is described starting from 5-(4-amino-3-nitrophenyl)-10,15,20

• [1,2-a]quinoxalinoporphyrins (4a–h) is depicted in Scheme 1. At first, 5-(4-amino-3-nitrophenyl)-10,15,20-triphenylporphyrin (1) was synthesized from 5,10,15,20-tetraphenylporphyrin (TPP) after a series of reactions [46][49] in five steps. The Clauson–Kaas reaction of porphyrin (1) with 2,5

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

• . The analytical and isolated yields of the reaction products are listed in Table 2. Compounds 3–5 were fully characterized using standard spectral methods. The structures of compounds 3а, 4b were confirmed by X-ray analysis (Figure 1). Furandiones 1a–c react with 3-(4-nitrophenyl)-2H-azirine (2c) to

• -azirine leads to an increase of yield of 1:2 adduct 3, and in the case of 3-(4-nitrophenyl)-2H-azirine (2c) it becomes the only product, while from 3-(4-methoxyphenyl)-2H-azirine (2b) only 2:2 adducts 4 and 5 were formed. It is also worth noting that in all cases the proportion of cis-isomer 4 was larger

• to an increase in the yield of 1:2 adduct 3, and in the case of 3-(4-nitrophenyl)-2H-azirine (2c) it becomes the only product, while from 3-(4-methoxyphenyl)-2H-azirine (2b) only 2:2 adducts 4 and 5 were formed. Calculations at the DFT B3LYP/6-31G(d) level for various routes of bis[1,3]oxazino[3,2-a

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• (M + 23). N-(2-(1H-Indol-3-yl)ethyl)-2-(3-nitrophenyl)-2-oxoacetamide (9e): 38% yield; mp 138.1–139.5 °C; IR (cm−1): 3364, 3331, 3121, 2860, 1662, 1523, 1346, 1263, 1212, 1098, 815, 752, 725; 1H NMR (400 MHz, CDCl3) δH 9.13 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 8.46 (d, J = 7.2 Hz, 2H), 8.09 (s, 1H, NH

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• ), (E)-3-(dimethylamino)-1-(3-nitrophenyl)prop-2-en-1-one (1 mmol) and 4-methoxyaniline (1 mmol). This three-component reaction was initially examined in solvents such as acetonitrile, dioxane, dimethyl sulfoxide, toluene and ethanol under heating. However, the only isolable product was compound 4d

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• then reacts with 7a to form the enamino ester 8a. Hydrolysis of 8a followed by cyclization affords 9 in 85% yield. The structure of 9 was unambiguously assigned by X-ray crystallographic methods (Figure 1). In contrast, we found that the p-nitrophenyl-substituted analogue 7b reacts with ethyl

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

• is achieved via an asymmetric addition of phenylethylzinc to the imine N-oxide 2.66 yielding the corresponding 3,4-dihydroisoquinoline-N-hydroxide 2.68. Further reductive cleavage of the hydroxylamine moiety followed by activation with 4-nitrophenyl chloroformate [79] yields the intermediate 2.69. In

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• catalyzed [3 + 2] cycloaddition reaction. Unfortunately, the yield for this reaction was very low (<20%). In order to obtain compound 1 by the 1,3 dipolar cycloaddition route we changed the protocol. We synthesized the nitro derivative 2 (3-tert-butyl-5-(4-nitrophenyl)-1,2,4-oxadiazole) in situ by using the

• ), 1522 (w), 1510 (m), 1491 (m), 1463 (m), 1442 (m), 1415 (w) 1394 (w), 1351 (s), 1329 (w), 1291 (w), 1197 (m), 1186 (s), 1172 (s), 1096 (w), 1028 (w), 962 (w), 845 (m), 835 (m), 777 (s), 700 (w), 645 (s) cm−1. Representative procedure for the synthesis of 3-tert-butyl-5-(4-nitrophenyl)-1,2,4-oxadiazole

• 4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)aniline (1). Atoms are drawn as 50% thermal ellipsoids. One hydrogen at N1’ is eclipsed. Packing diagram of compound 1. Hydrogen bonds are indicated as dashed lines. Molecular structure of 3-tert-butyl-5-(4-nitrophenyl)-1,2,4-oxadiazole (2). Atoms are drawn as 50

A simple, enaminone-based approach to some bicyclic pyridazinium tetrafluoroborates

• František Josefík,
• Markéta Svobodová,
• Valerio Bertolasi and
• Petr Šimůnek

Beilstein J. Org. Chem. 2013, 9, 1463–1471, doi:10.3762/bjoc.9.166

• preparation of 4-(4-methoxyphenyldiazenyl)-2-(4-nitrophenyl)-3-phenyl 5,6,7,8-tetrahydropyrido[3,2-c]pyridazin-2-ium tetrafluoroborate (5n) failed. A mixture of compounds 5k + 5m (approx. 1:2) was obtained instead. Crystallization of the mixture gave a mixed crystal (5k + 5m, for discussion of its structure

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• . Benzothiazole probes such as 83a,b and 84a,b labeled with [Re] and [99mTc] were also synthesized (Scheme 7A) [68][69]. [Re] and [99mTc]MAMA-BTA (83a and 83b; MAMA = monoamine-monoamide bisthiol-BTA) were prepared by first linking 2-(4-nitrophenyl)-6-hydroxybenzothiazole (85) via 1,5-dibromopentane (86) to

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• product 18. This compound was obtained in the form of crystals suitable for X-ray diffraction analysis. The molecular structure of 18 is shown in Figure 2A, confirming unambiguously its identity as N-(4-nitrophenyl)-3-fluoropropane-1-sulfonamide. Crystal data and structure refinement parameters are

• substrate 4-nitrophenyl butyrate in a spectrophotometric assay. The concentrations of 17 and 19 were monitored by RP-HPLC. As expected, sulfonamide 17 proved to be stable against degradation by carboxylesterase (Figure 6). Under the same conditions, fluoroacetamide 19 underwent degradation with a pseudo

• resulting sulfonamides was confirmed with the aid of the corresponding nonradioactive reference compounds. For one of these, N-(4-nitrophenyl)-3-fluoropropane-1-sulfonamide (18), the single-crystal X-ray structure was determined. The formation of 18F-labelled sulfonamides derived from aliphatic amines did

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• cyclooctenes have been used to examine the role of glycans in such processes such as neurite outgrowth [4], bacterial motility [5], and inflammation [6]. ROMP polymers with pendant reactive functional groups, such as N-hydroxysuccinimide (NHS) or nitrophenyl esters, are useful materials since the pendant

• modifications. Teoc deprotection under mildly basic conditions with tetrabutylammonium fluoride (TBAF) reveals the terminal primary amine, which can be subsequently coupled with a reporter molecule such as a dye. The terminating agent 3 was obtained by conjugation of 4-nitrophenyl (2-(trimethylsilyl)ethyl

Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins

• Satyasheel Sharma and
• Mahendra Nath

Beilstein J. Org. Chem. 2013, 9, 496–502, doi:10.3762/bjoc.9.53

• of a novel series of dihydro-1,3-oxazinoporphyrins. Results and Discussion The targeted dihydro-1,3-benzoxazinoporphyrins 6–9 were prepared in a three step procedure, starting from 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (1), which was obtained by the reduction of 5-(4-nitrophenyl)-10,15,20

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• of SF5 organics is their limited availability. In SF5-aromatics, para- and meta-nitro-(pentafluorosulfanyl)benzenes (3 and 4) (Figure 1) are available by the direct fluorination of the corresponding bis(nitrophenyl)disulfides [18][19][20], and several other SF5-benzenes are available through

Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

• Vijayanand Chandrasekaran,
• Katharina Kolbe,
• Femke Beiroth and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26

• . The determined IC50 values were referenced to the inhibitory potency of methyl α-D-mannoside (MeMan) and p-nitrophenyl α-D-mannoside (pNPMan), respectively, each tested on the same plate. Thus, relative inhibitory potencies (RIP values) were obtained, which allow comparison of inhibitory potencies of

• p-nitrophenyl α-D-mannoside (pNPMan). This result can be rationalised by computer docking, showing that regardless of the configuration of the N=N double bond of the azobenzene moiety in 2, favourable interactions can be formed with the tyrosine gate of the FimH CRD. While the terminal mannoside

Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution

• Dyanne L. Cruickshank,
• Natalia M. Rougier,
• Raquel V. Vico,
• Susan A. Bourne,
• Elba I. Buján,
• Mino R. Caira and
• Rita H. de Rossi

Beilstein J. Org. Chem. 2013, 9, 106–117, doi:10.3762/bjoc.9.14

• Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, Córdoba, Argentina 10.3762/bjoc.9.14 Abstract An anhydrous 1:1 crystalline inclusion complex between the organophosphorus insecticide fenitrothion [O,O-dimethyl O-(3-methyl-4-nitrophenyl

• pesticide against undesired degradation reactions. Fenitrothion [O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate] (1, Figure 1) is an organophosphorus insecticide and acaricide [3]. It is effective against a wide range of pests that damage forests and various crops and it can also be used in the