Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• (base 5). At the same time, in contrast to quinoquinoline 3, which sometimes adopts a twisted shape [11][13], molecule 5 each time remains almost flat. Nitration, nucleophilic methoxylation, and basicity measurements The nitration reaction of compound 5 should proceed in the same way as in other

• quinolines, at the benzene ring, and the resulting nitro compounds could potentially be subjected to further transformations, including nucleophilic substitution of nitro groups. Indeed, under the action of a small excess of the nitrating mixture, dipyridoacenaphthene 5 undergoes double nitration at

• results of 1H NMR spectra and TLC analysis, the second component was still present. This “permanent impurity” cannot be separated by chromatography or recrystallization, but it can be eliminated to some extent by washing the nitration products with hot chloroform, in which the impurity is slightly better

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• transformations of aryl substrates have also been reported for thiovinyl ethers, and also for dihydrodithiins (Scheme 5), although there are obvious limitations to this point of view. Classical electrophilic aromatic substitution procedures such as the Vilsmeier–Haack reaction or a simple nitration have been

• products (viz 16, Scheme 5b) [37]. Electrophilic aromatic substitution under less forcing reaction conditions of the same substrate 15, using a room temperature nitration procedure, does yield the expected mononitrated dithiin 17 in good yield, without desulfurization [38]. 1,4-Dithiin-2-carbaldehyde (18

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• nitration. A further strength of our route is divergency, additionally enabling the synthesis of 1-deazahypoxanthine (c1I base). Keywords: deazapurine; heterocycles; imidazopyridines; nucleoside; nucleotides; pyrrolopyrimidines; RNA atomic mutagenesis; Introduction Deazapurines (imidazopyridines and

• differed from the above path by leaving the hydroxy group of all intermediate 4-hydroxypyridine derivatives 12–15 unprotected [19]. Moreover, instead of azo coupling or nitroso formation, a simple nitration protocol with nitric acid to give the nitro derivative 13 and subsequent reduction with Raney nickel

• yields [22]. The switch from 2-tetrahydropyranyl to tert-butyloxycarbonyl protected compound 19 was required for an efficient installation of the exocyclic amine via regioselective nitration in the presence of trifluoroacetic anhydride (TFAA) and tetrabutylammonium nitrate (TBAN) to give a mixture of the

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• enzymes with tetranitromethane, a reagent for tyrosyl residue nitration, eliminated the cyclooxygenase activity, while the activity was not abolished in the presence of the cyclooxygenase inhibitor indomethacin, indicating that the tyrosine residue(s) is the catalytic center for endoperoxide formation

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

• ]metaparacyclophane and a cyclohexadienone cyclophane. Keywords: cyclophane; metaparacyclophane; nitration; paracyclophane; rearrangement; Introduction Cyclophanes have been described as having bent and battered benzene rings [1] due to a structure that involves one, or more, aromatic rings linked by aliphatic

• number of years [45][46][47][48][49][50][51][52], and have recently focused on 4-amino[2.2]paracyclophanes [14][53][54][55]. For the most part, we have avoided nitration. The literature is full of many different procedures, and the results can be unpredictable [55][56][57][58][59][60]. Yet nitration

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

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• required C3-symmetric tripyrroltruxene 6 by means of RCM in the presence of Grubbs′ first generation catalyst (G-I, 9) followed by self-aromatization without the involvement of any oxidizing agent. Compound 3 was produced from the hexabutylated truxene system 2 involving nitration, reduction and N

• , compound 2 was subjected to nitration followed by reduction to deliver triaminotruxene 4 in excellent yield. Later, compound 4 was subjected to six-fold N-allylation in the presence of NaH/allyl bromide to provide the required compound 3 which was directly treated with G-I catalyst (9) to afford the

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

• expand the library of derivatives containing core structure 13, electrophilic aromatic substitution of this compound was explored (Scheme 2). Nitration of 13 using 70% nitric acid in glacial acetic acid gave the corresponding regioisomers 14 and 15 in 53% and 41% isolated yield, respectively. The 1H NMR

• novel and may have a potential medicinal interest. Conclusion In conclusion, we have successfully synthesized hydroxy-substituted pyridobenzofuran 13. Furthermore, nitration of 13 yielded two regioisomers, 14 and 15, which were further converted to oxazoles 19 and 20. Formylation of 13 was

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• synthesis of the basic part was initiated by converting quinine to quinineamine via a Mitsunobu reaction, followed by a Staudinger reduction [40]. Then it was coupled with the acidic part, which was obtained by the nitration of 2,4,6-trimethylbenzenesulfonyl chloride [39] to obtain organocatalyst 5 (Scheme

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

• one of the most widely used fluorine-containing building blocks [48][49]. Recently, we have developed an efficient stereoselective synthesis of β-fluoro-β-nitrostyrenes 1 based on the radical nitration of 2-bromo-2-fluorostyrenes [50]. This process takes place with simultaneous elimination of bromine

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

• they are the most trustworthy strategies for direct functionalization of aromatic scaffolds [50]. As can be inspected from Scheme 18, monoiodosumanene 79 was obtained by gold-catalyzed iodination in the presence of N-iodosuccinimide (NIS). The mononitrosumanene 80 was achieved through the nitration

• separable regioisomers were obtained in moderate-to-good overall yields (Scheme 19). In similar fashion, trisubstituted sumanene derivatives were also prepared as shown in Scheme 19. The monochlorosumanene 88 was also reported by Amaya and Hirao in three steps from the sumanene (2) using a classic nitration

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• challenges since the solubility of CAN in organic solvents determines the likelihood of nitration or oxidative dimerization [1]. It was found that dry acetonitrile was more conducive to nitration, whereas methanol afforded the desired biaryl in 55% yield. In contrast to CAN, both V2O5 and CrO3 required

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• protected biscarbazolyl derivative 7. TFA was used for deprotecting 7, which led to the corresponding free amine derivative 8 that could directly be used for cyclization. We were unable to successfully follow all steps in the synthesis scheme by Sanchez et al. [6]. The problematic step was the nitration

• reaction. Due to the highly acidic environment partial loss of one of the tert-butyl groups in 2 took place. This considerably reduced the yield and resulted in a mixture of products 3a and 3b that was challenging to separate due to similar properties. Careful optimization of the nitration process did not

• reference [6]. It is worth noting that the described cleavage problem during nitration was specific to tert-butyl groups. We also studied the possibility of hexyl substituents instead of tert-butyl groups [25]. In this case, the nitration process yielded only the desired product. However, since this

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• group hinder the electrophilic modification at the 3-position. Generally, the aryl group is introduced by a Suzuki–Miyaura cross-coupling reaction [4][5], for which 3-bromo-4-nitrophenol must be prepared by the nitration of 3-bromophenol [6][7]. An alternative approach is the nitration of 3-arylphenol

• [8][9]. However, these nitration methods are less effective because the yield of the desired product is reduced by the formation of regioisomers. Although the hydroxylation of 3-arylated-1-fluoro-4-nitrobenzene has also been reported as a related strategy, multistep reactions are necessary for

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• assembled using this strategy, as displayed in Scheme 15, and a plausible mechanism for the reaction is shown in Figure 16. C–H nitration of protected anilines Nitroanilines are an important class of compounds and found in many drugs and dyes [144]. Therefore, recently, König and co-worker reported the

• in the literature, earlier methods applied harsher conditions, such as a strong acid and high temperature. Although in some cases, a mild nitration agent such as tert-butyl nitrite (TBN) was used, the reaction required an elevated temperature [146][147][148][149][150]. As can be seen in Figure 17

• catalyst. Proposed mechanism for the trifluoromethylation of 88. Plausible mechanism for the synthesis of substituted coumarins. Mechanism proposed for the phosphonylation reaction of 100. Plausible mechanism for the nitration of aniline derivatives via photoredox catalysis. Proposed mechanism for the

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

• of azo, nitro, and amino derivatives of 6-hydroxy-2,3-benzotropone (239) (Scheme 42) [164]. While 7-amino derivative 264 was prepared via diazo coupling of 239 with diazotized p-toluidine in a pyridine solution followed by hydrogenation, the nitration of 239 in acetic acid solution afforded nitro

• ) [174]. Catalytic hydrogenation of 241 over Adams's catalyst (PtO2.H2) gave the diol 295 (Scheme 49) [162][165][174]. Treatment of 241 with alkaline hydrogen peroxide caused degradative fission to give o-carboxycinnamic acid (296) [165], while nitration of 241 with nitric acid in an acetic acid solution

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• ]. Classical nitration methods have, however, many drawbacks concerning elevated reaction temperatures, long reaction times, and poor yields. The introduction of amino or substituted amino groups onto ring A of estrone is fascinating from both organic chemical and biological points of view. Certain ring A

• -aminated estrone derivatives are described as inhibitors of estrogen biosynthesis. They are often synthesized via a three-step method including nitration, reduction, and functionalization of the amino group [1][2]. This three-step protocol may be simplified to involve only one or two steps by the

• coupling procedure, the synthesis of 2-amino-13α-estrone 13 could be achieved in only two steps without the first, aromatic nitration step used extensively earlier. The newly synthesized amino derivatives of 13α-estrone 5–13 may possess important biological activities without hormonal effect. Pd-catalyzed

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• % overall yield, Scheme 8). In the key transformation, the mannose residue at the reducing terminus was then converted into a glucosamine derivative (in fact possessing an azide at C2) first by conversion to the glycal and then an azido nitration reaction. This innovative method is considerably shorter than

Nitration of 5,11-dihydroindolo[3,2-b]carbazoles and synthetic applications of their nitro-substituted derivatives

• Roman A. Irgashev,
• Nikita A. Kazin,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2017, 13, 1396–1406, doi:10.3762/bjoc.13.136

• , Russia 10.3762/bjoc.13.136 Abstract A new general approach to double nitration of 6,12-di(hetero)aryl-substituted and 6,12-unsubstituted 5,11-dialkyl-5,11-dihydroindolo[3,2-b]carbazoles by acetyl nitrate has been developed to obtain their 2,8-dinitro and 6,12-dinitro derivatives, respectively. A

• both nitro groups, unlike potassium salts of indole or carbazole, which have caused substitution of only one nitro group. Keywords: electrophilic aromatic substitution; indolo[3,2-b]carbazole; N-heteroacenes; nitration; nucleophilic aromatic substitution; Introduction Organic π-conjugated compounds

• ICZs [37], as well as C2- and C2,8-bromination of 6,12-disubstituted ICZs [23][38]. Bromo-containing ICZ derivatives have also been involved in further lithiation and metal-catalyzed cross-coupling reactions. Herein, we describe an effective protocol for nitration of 5,11-dihydroindolo[3,2-b]carbazoles

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• has been reported that nitration and bromination of 2 take place at the 1-position (however, the bromine atom in 1-bromopyrene can migrate into the 4-position in the presence of AlCl3) [8][9], whereas Friedel–Crafts acylation and Vilsmeier formylation take place at the 4-position [10]. We recently

Molecular-level architectural design using benzothiadiazole-based polymers for photovoltaic applications

• Vinila N. Viswanathan,
• Arun D. Rao,
• Upendra K. Pandey,
• Arul Varman Kesavan and
• Praveen C. Ramamurthy

Beilstein J. Org. Chem. 2017, 13, 863–873, doi:10.3762/bjoc.13.87

• , 1,2-difluorobenzene was reacted with trimethylsilyl chloride in the presence of lithium diisopropylamide to afford the 1,4-disilylated intermediate 4 and bromination of the latter compound in neat bromine afforded the desired 1,4-dibromo-2,3-difluorobenzene (5). Nitration of 5 by treatment with fuming

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• standard nitration conditions to obtain the desired dye eosin B (4) (Figure 1). The NMR spectra showing the structure elucidation of the free dyes eosin Y (2) and eosin B (4) are shown in Supporting Information File 1, Figures S3–S7 and Figures S15–S19, respectively. Synthesis of eosin Y–β-CD and eosin B–β

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• synthetically relevant intermediates (precursors of baclofen and boscalid). Keywords: chemoselectivity; continuous processes; flow synthesis; nitro reduction; trichlorosilane; Introduction The reduction of nitro compounds to amines is a fundamental transformation in organic synthesis. The nitration of

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• slightly reduced reaction yield on this scale. For scale-up of the DABCO-catalysed cyanation, 6 was synthesised by straight-forward nitration of the significantly cheaper starting material 2-chlorobenzothiazole (16) [15], and isolated in 82% yield after crystallisation from ethanol (Scheme 3

Amidofluorene-appended lower rim 1,3-diconjugate of calix[4]arene: synthesis, characterization and highly selective sensor for Cu²⁺

• Rahman Hosseinzadeh,
• Mohammad Nemati,
• Reza Zadmard and
• Maryam Mohadjerani

Beilstein J. Org. Chem. 2016, 12, 1749–1757, doi:10.3762/bjoc.12.163

• 1 afforded the 5,11,17,23-tetra-tert-butyl-25,27-di(hydroxycarbonylmethoxy)-26-28-dihydroxy calix[4]arene (2) in high yield. Coupling of this diacid 2 with 9H-fluoren-2-amine (4, obtained from nitration of fluorene and reduction of the resulting 2-nitrofluorene, (3)) in the presence of N,N