On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• aromatic substitution reaction. The substrate failed to give the same product when subjected to alkylation with the isolated putative iminium ion intermediate. The authors then suggested the reaction took place through a radical mechanism instead. This vanadium-mediated aminoalkylation reaction was found

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• in determining ring closure either via path a or path b. In path a, the protonation of the imine nitrogen in 7a by the conjugate acid (+ BH) leads to an electrophilic aromatic substitution at the 3-position of the indole unit to form a carbon–carbon bond in the intermediate 8. A further proton

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• the chemistry of naphthalene. The last one dates from 1887 and deals with the formation of isomers in the electrophilic aromatic substitution of naphthalene with chlorine and bromine [32]. This work was done in collaboration with Pietro Biginelli (1860–1937), the only collaborator of Guareschi who

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

• to hydroquinone 12 with N,N-diethylhydroxylamine (N,N-DEHA) and cyclized via intramolecular nucleophilic aromatic substitution to isolate 6-hydroxybenzofuro[2,3-b]pyridine (13) with 82% yield. Conveniently, the synthesis of 13 was achieved in a one-pot reaction from 11 with no significant differences

• 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

• . Electrophilic aromatic substitution of 6-hydroxybenzofuro[2,3-b]pyridine (13). Synthesis of isomeric oxazole-fused derivatives. Fused derivatives from 16. Supporting Information Supporting Information File 164: Experimental part as well as 1H and 13C NMR data. Funding We thank the KU Leuven for financial

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 N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• of pyrroles to the 3,4-disubstituted derivatives is challenging because an electrophilic aromatic substitution of pyrroles or the metalation of N-substituted pyrroles and the subsequent reaction with electrophiles take place in position two of the ring [6][7]. Recently, N-sulfonyl-1,2,3-triazoles

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• ring at the C6 position of purine to act as leaving group. Keywords: 2,6-bistriazolyl purines; nucleophilic aromatic substitution; purine nucleosides; triazoles; Introduction Modified purine derivatives are an important class of compounds which possess a wide spectrum of biological activities [1][2

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• . Keywords: Arbuzov reaction; 2,6-bistriazolylpurines; nucleophilic aromatic substitution; purinylphosphonates; Introduction Acyclic nucleoside phosphonates (ANPs) are an important compound class due to their biological activity profile [1][2][3][4][5][6]. Compounds bearing a phosphonate moiety in their N9

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• ), complex mixtures were obtained with less than 5% conversion to the desired amide product 31. The library process was completed by carrying out the nucleophilic aromatic substitution with a 3-fold excess of amine in DMF at 60 °C overnight to afford 32a–h, after a removal of Boc or Cbz groups [20] where

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• nowadays a growing interest in the forging of Ar–Ar bonds under transition-metal-free conditions [24][25]. Apart the most common pathways, e.g., the Friedel–Crafts functionalization [26] or nucleophilic aromatic substitution [27], alternative approaches have emerged that make use of photogenerated

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• obtained with DeoxoFluor at elevated temperature (Scheme 2). A side-product in this fluorination reaction was the tricyclic compound 12, which presumably formed through an electrophilic aromatic substitution reaction of the activated alcohol intermediate. The inclusion of TMS-morpholine [29] reduced the

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• Dommaschk et al. [4][27]. Synthesis of azopyridines 11, 14, 16 and 18 by nucleophilic aromatic substitution. Synthesis of 3-(3-bromophenylazo)-4-cyanopyridine (20), which was hydrolyzed to yield 3-(3-bromophenylazo)-4-pyridinecarboxylic acid (21). Modular approach for the C–C connection of the Ni(II

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

• crystal of sumanene derivative 82 by means of time-resolved microwave conductivity technique. On the other hand, four years later, Sakurai and his teammates have reported the selective synthesis of diverse monosubstituted sumanene derivatives by employing electrophilic aromatic substitution reactions as

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• cyclobutene and several cationic intermediates and mainly yield 2-(1-phenylvinyl)indenes. In a similar reaction cascade, a fulvene derivative was obtained with 1,4-diphenylbutadiene as the substrate. Keywords: alkynes; aromatic substitution; cyclization; cycloaddition; iminium salts; Introduction In recent

• °C, 19F NMR monitoring of the reaction’s progress indicated the appearance of a second product beside the 1,4-cyclohexadien-1-iminium salt 4-Ch. Further investigations revealed that the new product was the dihydrofluorene 7, resulting from 4-Ch by an intramolecular electrophilic aromatic substitution

• propyn-1-iminium ion via its C3-position to the olefinic bond of styrenes initiated a reaction cascade which was again terminated by the already mentioned cyclization step through intramolecular electrophilic aromatic substitution, resulting in the formation of 2-(1-phenylvinyl)-1-(trifluoromethyl)-1

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• second step, the naphthalene nucleus was functionalized via a nucleophilic aromatic substitution with the Boc-protected amino acids ʟ-Dap and ʟ-Lys. The reaction was carried out in dry DMSO at 60–65 °C for 1.5–2 hours. After two preparative HPLC purifications in an acidic environment (with TFA) and

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• preparation of phenanthridines with the intermediacy of imidoyl radicals. As an example, the process depicted in Scheme 10 involved a visible-light homolytic radical aromatic substitution (HAS) starting from trifluoroacetimidoyl chlorides 10.1a–e. Thus, the photocatalyzed cleavage of the C(sp2)–Cl bond in

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• . The developed methodology is capable of predicting reactivity of various substrates by differentiation between two major mechanisms – proton abstraction and electrophilic aromatic substitution. An attempt has been made to predict new C–H activation reactions. This methodology can also be used for the

• was proposed for classifying whether the carbon atoms are active or inactive toward electrophilic aromatic substitution [17]. Also, a quantum mechanical approach was introduced to compute ortho-directing groups (DGs) in palladium-catalysed aromatic C–H activation reactions [18]. However, there is a

• : a) electrophilic aromatic substitution (SEAr) mechanism and b) proton abstraction (PA) mechanism. The key step for the electrophilic aromatic substitution is an electrophilic attack by Pd(II) onto the aromatic substrate that also defines the regioselectivity of the overall process [24]. The key

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• , bearing a quinazoline unit as the acceptor core and carbazole, dimethyldihydroacridine, or phenothiazine donor moieties, were designed and synthesized in two steps including a facile copper-catalyzed cyclization and a nucleophilic aromatic substitution reaction. The photophysical properties of the

• nucleophilic aromatic substitution reaction. The dimethyldihydroacridine and phenothiazine-containing quinazoline compounds formed molecular glasses with glass-transition temperatures of 123 °C and 116 °C, respectively. The ionization potentials estimated by cyclic voltammetry of the derivatives were found to

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• ][8]. Every student of organic chemistry is taught the importance of arenium ions in the classic two step SEAr mechanism for electrophilic aromatic substitution. Addition of an electrophile to an arene leads to a bound species, sometimes called a σ-complex, which then loses a proton at the site of

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• trans-6e as an orange solid with 97% purity. The synthesis of compounds 6f–h was performed following a nucleophilic aromatic substitution route on 28b (Scheme 4) since precursors 8 or 17 with the required substituent Y were not available. We performed nucleophilic aromatic substitutions with the

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• pyridinyl motif. In fact, only two pyridinyl silicon rhodamines (13 and 14) are known so far, although halogenated pyridines are highly interesting for further functionalization or vector conjugation by nucleophilic aromatic substitution. For the implementation of the dihalogenated pyridine motif into the

Synthesis and properties of sulfur-functionalized triarylmethylium, acridinium and triangulenium dyes

• Marco Santella,
• Eduardo Della Pia,
• Jakob Kryger Sørensen and
• Bo W. Laursen

Beilstein J. Org. Chem. 2019, 15, 2133–2141, doi:10.3762/bjoc.15.210

• influence the overall reactivity of the system towards subsequent nucleophilic aromatic substitution. When the reaction was followed by MALDI–TOFMS spectrometry it was thus possible to observe simultaneously the presence of the target compound and all of the intermediates involved in the reaction. This

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• probably deprotonation of the heterocyclic rings with a base. Moreover, nucleophilic aromatic substitution (SNAr) reactions between an aryl halide and a selenium reagent such as aryl selenide anion or diaryl diselenide for C(Ar)–Se bond formation using a base have been reported [20][21][22]. However, the

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• operational one-pot reaction fashion on the basis of a nucleophilic aromatic substitution reaction [23][24][25][26][27][28][29][30][31]. To prepare functionalized corona[6]arenes using diethyl terephthalate as a starting material, we observed, however, the formation of a mixture of macrocyclic isomers because

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165