A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• , i.e., benzyl and ethyl, slightly decreased the yields of the products (see 4n and 4o). Regrettably, when a substrate 2 bearing a strong electron-withdrawing nitro or trifluoromethyl group on the phenyl ring was employed, the reaction gave very complex side products under the standard conditions, and

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• conditions A and B, highlights the steric influence of the halogen C-3 substituent. Furthermore, Bookser et al. have noted comparable regioselectivity with related C-3 bromo substituted N-containing heterocycles, under similar reaction conditions [24]. Marked N-1 regioselectivity was achieved with 3-nitro

• the corresponding N-2 regioisomer (Table 4, entries 1 and 2). This latter preference for N-2 alkylation is likely due to the proximal steric bulk of both the C-7 Me and Br substituents, respectively, to the N-1 position. The presence of a nitro or methyl carboxylate group at the C-7 position of the

• ) was extended to indazoles bearing a nitro (19) or carbonyl (21–24) functional group, the desired N-1 regioisomer was obtained with a very high degree of regioselectivity. In the case of C-3 substituted indazoles 9, 19 and 21–24 (those bearing a X=O α to the indazole C-3 position), we postulate that in

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• )-27-6. Enantioselective fluorinations of typical enolates were then performed (Scheme 63). The (R)-27-6 reagent gave up to 79% yield and 88% enantiomeric excess in the case of 2-benzyl-α-tetralone. 1-28. (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-benzothiazine 1,1-dioxides and spiro-type analogues In

• 2000, the Takeuchi group reported their second series of chiral N-fluorosultam reagents, (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxides 28-3 [93] (Scheme 64). Racemic 28-1 reacted with (+)-10-camphorsulfonyl chloride to give a mixture of the diastereomers

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• undoubtedly the result of the lengthy syntheses of these compounds. We report the simple synthesis of a rare example of a non-symmetric [2.2]metaparacyclophane. Treatment of [2.2]paracyclophane under standard nitration conditions gives a mixture of 4-nitro[2.2]paracyclophane, 4-hydroxy-5-nitro[2.2

• obviously presents one of the most direct routes to 4-amino[2.2]paracyclophanes so we returned to this venerable reaction. In this paper, we disclose a simple synthesis of 4-hydroxy-5-nitro[2.2]metaparacyclophane (5), a side-product from our nitration reactions. This chemistry offers a rapid route to non

• polymerization. Extensive optimization led us to a set of conditions that routinely provided 4-nitro[2.2]paracyclophane (4) in good yields regardless of the scale of reaction (nitration has been performed on scales ranging from 0.5 g to 30 g). The 1H NMR of the crude reaction mixture invariably shows two other

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• Fmoc chloride to accomplish an orthogonal protective group strategy. The removal of the Boc groups from compounds 5 with TFA gave the mixed aniline and nitro precursors 6. In previous approaches, the nitro groups were reduced to hydroxylamines with zinc and oxidized to the corresponding nitroso

• compounds with iron(III) to perform an intramolecular Baeyer–Mills reaction [15][21]. We found that a complete reduction of the nitro group to aniline 7 and oxidation with mCPBA is increasing the yield of the intramolecular cyclization from 39% to 62% (over two steps) for the unsubstituted diazocine 8c as

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• -vinylnaphthalen-2-yl)acetaldehyde (13h) was prepared from 1-bromo-2-naphthaldehyde in 48% yield over the three steps. It should be noted that the nitro-substituted intermediate 11d was prepared by nitration of 11a with nitric acid under the promotion of acetic anhydride. With the accessibility of the aromatic

• in 38–72% yield. To our gladness, aldehyde 13d, with an electron-deficient nitro group residing on the benzene ring reacted with veratrole under the standard conditions, delivering tetralin 14da in 55% yield. However, using furan as the nucleophile component, the reaction sequence with 13d failed to

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• ]. Herein, we report a better enantioselective version of the reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones (Scheme 1). Results and Discussion Initially a model reaction was examined between N-benzyl-4-benzylidenepyrrolidine-2,3-dione (1a) and 2-nitro-1-phenylethanone (2a) in the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• direct C–C and C=C bond-forming tool which has been widely described in the literature to prepare a range of different valuable intermediates [127][128][129][130][131]. Applications in the F&F industry are sparse which is probably due to the unpredictable nature of some nitro intermediates. However, late

• in 1983, Ballini et al. represented the potentiality of the reaction for the synthesis of dihydrojasmone derivatives (Scheme 20) [132]. Flow chemistry embodies the safest conditions for handling hazardous chemicals, therefore opening new opportunities for nitro compounds to be industrially employed

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• reproducible protocol to isolate the product without the use of any organic solvent was established, and the recyclability of the DES mixture was successfully investigated. Keywords: alternative solvents; atom economy; DES; nitro derivatives; reduction; Introduction The search for alternative solvents, not

• , nitrocyclohexene was reduced in 60% yield in a ChCl/glycerol mixture, while 6c was obtained in similar yields in glycerol or DES B. Noteworthy, the reduction of nitrobutadiene 5d produced nitro derivative 6d in 63% yield in glycerol and 44% in DES B, with complete control of the chemoselectivity. Remarkably, the

• reduction of nitrodiene 5e, featuring an ester group, was also accomplished with complete chemoselectivity in 50% yield in DES B and in 60% yield in glycerol. The reduction of the nitro group to an amine, followed by cyclization would afford the unsaturated δ-lactam, a valuable precursor for further

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• , presumably caused by the nitro group that is known to be an efficient emission quencher. It was demonstrated with experiments in glycerol solution that the emission of 5a–d increases also upon suppression of conformational freedom of the molecule in media with high viscosity and limited free volume (Figure 2

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• unknown compounds 14–16 opens many synthetic possibilities for the preparation of novel fused derivatives of 1-aza-9-oxafluorene. The nitro compounds 14 and 15 were reduced to the corresponding aniline derivatives using hydrogen and Pd/C as a catalyst. The resulting aminophenols 17 and 18 were further

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• with alcohol 307 to obtain 309 (Scheme 71) [113]. The introduction of electron-withdrawing nitro groups on the BINOL backbone in the catalysts significantly enhanced the reactivity and enantioselectivity. Zhou et al. reported an asymmetric Prins cyclization of in situ-generated quinone methides from

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• be prepared via two similar procedures previously described in the literature [17][18]. Our synthetic route is based on the protocol offered in T. Pelkey’s publication [18] using DMF as a solvent for the nucleophilic aromatic substitution of the nitro group in 2-nitrobenzaldehyde (1) instead of the

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• 5.7–6.4 (series 5), 5.3–5.9 (series 6), and 5.0–5.5 ppm (series 7), except for the nitro derivatives (R1: 5-NO2) where the nitro group always enhances the Ar–H4 chemical shift by about 0.7 ppm. Therefore, a 2D-NOESY experiment was performed for some representative 5-NO2 derivatives (5eb–ed) confirming

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• for esterases [23][38]. The alkylation of 4NTC with homoallylic bromide under basic conditions gave a mixture of mono- and dialkylated 4NTC derivatives, with 10 (38%) predominating because of the preferential formation of the phenolate at the para-position (relative to the nitro group) [39]. Osmium

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• , and gives the target structures solely in the Z-isomeric form in high yields (up to 92%). These fluorine-containing olefins activated by a nitro group proved to be the appealing building blocks for the construction of numerous monofluorinated compounds [51][52][53][54][55][56]. This paper is devoted

• indicate an isomer as exo or endo according to the stereo-position of the fluorine atom. Thus exo-2 and endo-2 means 5-exo-fluoro-5-endo-nitro-6-exo-arylnorbornene and 5-endo-fluoro-5-exo-nitro-6-endo-arylnorbornene, respectively (Figure 1). Both diastereomers are formed in a nearly 1:1 ratio for the

• majority of the substituents on the aryl group of the nitrostyrenes 1. However, a higher diastereoselectivity towards the endo-isomer was observed when strong electron-withdrawing groups (EWGs) were present in the dienophile. For example, in the case of the 4-cyano and the 3-nitro-substituted derivative

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• of iodofluorobenzene derivatives with nitro-cyanostilbenes is reported. The systematic variation of the fluorination degree and pattern indicates the relevance of the halogen bond strength for the induction of liquid crystalline properties. The modular self-assembly approach enables the efficient

• behaviour of halogen-bonded liquid crystals has been reported. In 2014, Tothadi and Desiraju reported on a new supramolecular synthon based on the non-covalent interaction between 1,4-dinitrobenzene and iodobenzene [13]. Their structural analysis of a series of ternary cocrystals revealed that the nitro

• entities [14][15][16][17]. However, no examples for supramolecular materials employing this complementary interaction have been reported so far. In the present study we report the first halogen-bonded liquid crystal based on the complementary binding of nitro-cyanostilbene and tetrafluoroiodobenzene

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• reacted with 2,6-dimethylpyridine (1a) to obtain the corresponding products 3a–r with a moderate to excellent yield (Table 2). The substrates 2a–d with nitro substituents were well reacted to achieve the desired products 3a–d in 68–95% yield (Table 2, entries 1–4). Distinctly, 2-nitrobenzaldehyde (2c

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• being slightly tilted out of the cavity. The corresponding interplanar angles Φ with the aromatic subunits are 81.55°, 80.78°, 77.08°, and 80.57°, respectively, starting counterclockwise from the upper subunit bearing a nitro group (Figure 2a). The 1,3-alternate isomer 4a represents quite an interesting

• the nitro groups or (ii) concomitant reduction of the nitro groups and the allyl moieties. Thus, the reaction of 4a with SnCl2∙2H2O in ethanol gave the corresponding amine 5 in 57% yield after column chromatography on alumina. On the other hand, the four-day stirring of 4a with Pd/C under a H2

• calixarene. Comparing the complexation constants for the otherwise identical receptors (7a vs 8a or 7b vs 8b), it is obvious that the presence of allyl vs propyl substituents does not impose much difference in terms of absolute K values and selectivity. As expected, the nitro-substituted receptors 7a and 8a

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• (hetero)aromatic units and either electron-donating (methyl, methoxy) or electron-withdrawing groups (carboxy, nitro, etc.) pending on the imine substrate. The molecular structures of all synthesized α-(arylamino)acetonitriles 2a–j were fully characterized by spectroscopic methods. The MS spectra

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• superior electrophile in comparison to the ester function. Indeed, this bielectrophilic reagent reacted only at the nitro group, providing the amide 20 as the sole product. The yield was quite marginal, primarily due to decomposition of the fragile ester functionality under the harsh reaction conditions

• bar was charged with 2-nitro-1-phenylethan-1-one (1h, 330 mg, 2.00 mmol), 2-picolylamine (12, 108 mg, 1.00 mmol), 87% polyphosphoric acid (500 mg), and phosphorous acid (500 mg). The flask was capped with a septum, placed into an oil bath preheated to 160 °C, and stirred for 2 h. Upon reaction

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• with carbon disulfide [26], diphenylketene [27], β-nitrostyrenes [28][29], if ionic liquids (IL) were used as reaction media. The reaction of β-nitrostyrenes with azomethine imines proceeds giving mixtures of Michael and anti-Michael-type adducts, containing a nitro group at the C2- or C1-position of

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• nitrogen heteroatoms were synthesized in multistep synthetic routes. A Buchwald–Hartwig amination of brominated precursors, thermolysis of azide precursors, and a Cadogan reaction of nitro-substituted precursors were successfully applied to eventually build-up pyrrole rings to stable and soluble fused

• of azide precursors, and a Cadogan cyclization of nitro-substituted precursors were applied to prepare various unknown derivatives. These represent novel core molecules, which by further derivatisation, for example with terminal acceptor groups, would lead to interesting π-conjugated materials for

• derivatives by Cadogan reaction of nitro-substituted precursors. Another possibility for the preparation of fused pyrrole rings is established by the Cadogan reaction [40]. Well-known examples are the reductive cyclization of 2-nitro-1,1’-biphenyls with triethyl phosphite or phosphanes as reducing agent to