Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• multicomponent reaction of the same starting materials led to the formation of only tetrahydrotriazolopyrimidine derivatives. Keywords: 5-amino-1,2,4-triazole; heterocyclization; multicomponent reaction; salicylaldehyde; ultrasonication; Introduction Multicomponent reactions (MCRs) are a powerful tool for the

• I–VI were formed (Scheme 1) [8][18][19]. It is known that substituents in aminoazoles can significantly influence their behavior in multicomponent heterocyclization reactions [4][8][20][21]. However, the reactions of 5-amino-1,2,4-triazoles containing substituents in position 3, which can also

• are shown at 50% probability level. Diversity of heterocyclization products from reaction of aminoazoles with salicylaldehydes, and pyruvic acids. MCRs of 3-amino-5-methylthio-1,2,4-triazole (1a) and 3-amino-5-methoxy-1,2,4-triazole (1b) with salicylaldehydes 2a–f, and pyruvic acid (3). MCRs of 3

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• , LV-1006, Riga, Latvia 10.3762/bjoc.21.154 Abstract A novel copper-catalyzed arylation strategy for propargylsilanes utilizing diaryl-λ3-iodanes has been developed, enabling a cascade sequence involving 1,2-silyl migration and heterocyclization. The β-silicon effect facilitates the formation of

• indicates that the provided method is limited to propargylsilanes containing a terminal alkyne group. Arylation of internal nucleophile-containing propargylsilanes Internal nucleophile-containing substrates are interesting, because they offer the possibility of heterocyclization, as described in our

• -butyldimethylsilyl)hex-5-yn-1-yl)-N-phenylaniline (15). Thus, acylamides were found to have optimal pKa and nucleophilicity to react according to our desired pathway (Scheme 4). For the heterocyclization mechanism under arylating conditions, we propose a Cu(I/III) catalyzed pathway (Scheme 5). Firstly, the copper(I

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• of the synthesized compounds were proven by a set of physicochemical methods, including X-ray diffraction analysis. Keywords: CH-acids; 1-halo-1-nitroethenes; heterocyclization; nitroacrylates; X-ray diffraction analysis; Introduction The combination of the furan ring with various carbo- and

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• testing confirmed that oxidation of the pyridyl-containing amines results in the intramolecular heterocyclization yielding pyridoindazolium salts. The reduction of N-arylpyridoindazoliums in the presence of a source of protons restores the starting diarylamines. Redox-interconversion between diarylamines

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• aromatic amines (Scheme 34). The GBB-like multicomponent reaction was carried out under MW heating. The initial condensation of the three precursors was catalyzed by I2, providing electron deficient ketoimines 108. The intermediates 108 underwent intramolecular heterocyclization to furnish the fused

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• heterocyclization reactions by exploiting the electrophilic character of Pd(II) species. Starting from substrates bearing a triple bond and a nucleophile in the appropriate position, a versatile process of heterocyclization can be initiated, resulting in indole derivatives with important properties. Gabriele et al

• years later, they performed, using the same catalytic and oxidative conditions, another oxidative heterocyclization/alkoxycarbonylation process for the synthesis of N-substituted indole-3-carboxylic esters and N–H free indole-3-carboxylic esters from N-substituted 2-alkynylanilines and 2-alkynylanilines

• %, respectively) in methanol under 90 bar of CO at 100 °C for two hours (Scheme 6). As already seen, triple bonds can be activated by Pd(II) catalysts towards the addition of nucleophiles in the right position, leading to heterocyclization reactions. Taking advantage of this possibility, in the Della Cá group, a

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• equivalents to react with various nucleophilic reagents [90]. In 2014, Heimgartner et al. first developed the condensation reaction of a commercially available fluoral hemiacetal with acylhydrazides to yield trifluoromethylated acylhydrazones, and these fluorinated compounds underwent heterocyclization

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• of samples 5b, 5d, and 5e suitable for X-ray diffraction studies (Figure 3 and Figure 4). Crystals of compound 5c were grown up using CHCl3/EtOH solvent, and it was unexpectedly found that keeping this compound in the above system for a month leads to its partial heterocyclization to benzo[g]indole

• -terminated butadiyne 5 gradually underwent demethylation/acid-catalyzed heterocyclization involving one of the dimethylamino groups and the adjacent C≡C bond of the butadiyne linker, forming the corresponding benzo[g]indole derivative. Proton sponge-based 1,4-diaryl-1,3-butadiynes synthesized previously and

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• -catalyzed hydrophosphinylation [45]. The key heterocyclization of 11 into 12 was accomplished using silver-promoted homolytic aromatic substitution [46], which was superior to our own manganese methodology (43% yield) [36]. Copper-catalyzed arylation [34] of 12 with iodobenzene and 4-nitroiodobenzene gave

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• involving the addition of arylamines to β-NQS 18 followed by N-alkynylation and then Cu(I)-catalyzed heterocyclization with tosyl azide in toluene at room temperature, leading to triazoles 50c–k in moderate to excellent yields (Scheme 14). The research group that most explored the formation of heterocycles

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• heterocyclization, optimization of the reaction conditions was performed. The solvent, reaction temperature and time, as well as the reagent ratio were varied. Since CH2Cl2, CH2Cl2–TFA, and 2,2,2-trifluoroethanol (CF3CH2OH, TFE) are used most often for the reactions with PIFA, these solvents were evaluated in the

• reaction proceeded with high regioselectivity as 5-exo-trig cyclization. The substituent in the quinazoline ring had virtually no effect at the yield or selectivity of the heterocyclization. Two pathways seem to be possible for the oxidative heterocyclization of quinazolinones 7 (see Scheme 2). The first

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

• traces of any β-carboline product were observed, which proves that the heterocyclization reaction is highly regiospecific. Optical properties of γ-carbolines Interestingly, the γ-carboline derivatives were found to be highly fluorescent under UV light irradiation. A systematic literature survey revealed

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• derivatives have been hitherto unknown due to their synthetic inaccessibility by the conventional approach based on the formation of the pyrimidine moiety. For example, the attempted heterocyclization of ethoxyenones II (e.g., 4-ethoxy-1,1,1-trifluorobut-3-en-2-one) with N-arylureas, unlike the reaction with

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• observed in the case of 6-trifluoromethyl-2-thiouracil that afforded 2- and 3-phosphonylated 5-oxothiazolopyrimidines in a 1:1 ratio. Keywords: chloroethynylphosphonate; heterocyclization; phosphonylated thiazolopyrimidines; phosphonylation; thiazolopyrimidine; 2-thiouracil; Introduction

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• electron-donating groups like MeO. Studies to expand even more the scope and the selectivity of such DES-promoted heterocyclization reactions and to elucidate their mechanism are in progress. Experimental General methods Deep eutectic solvents [choline chloride (ChCl)/glycerol (Gly) (1:2 mol/mol); choline

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• -aminopyrazoles bearing an electron-withdrawing substituent in the 4-position, such as a carbonitrile group, often behave similar to 3-amino-1,2,4-triazole; therefore, we studied the latter under the same reaction conditions. We showed that the pseudo four-component heterocyclization of two equivalents of 3-amino

• heterocyclization of 5-aminopyrazole 1a and p-methoxybenzylidenepyruvic acid (8, obtained from p-methoxybenzaldehyde and pyruvic acid) under the same conditions in a much shorter reaction time (10 min) with 66% yield (Scheme 5). The results presented above indicate that the reaction possibly proceeded under kinetic

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• % for thioaroyl derivatives, and compares favourably with the literature data [57] for 3a (85 vs 62%, respectively). Compounds 3j,l,m afforded slightly lower overall yields. Synthesis of tetrahydro-1,3-thiazepines With the required precursors in hand, we examined next the MW-assisted heterocyclization

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

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• substituent of the arylaldehyde is in para-position, but decrease with the substituent in ortho-position, likely due to steric hindrance that limits the cyclization process. In terms of electronic effect, electron-withdrawing groups (e.g., F, Cl, Br, NO2) favor the heterocyclization, but electron-donating

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• individual spiro compounds, not to a mixture of substances. However, condensations with the use of N-unsubstituted isatins are accompanied by the resinification of the reaction mixture, which may be caused by competing reactions of heterocyclization of the mentioned Knoevenagel adducts. In similar reactions

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• interest as so-called ‘nitrone like’ reagents for the synthesis of more complex, imidazole containing systems (Scheme 1) [6]. These imidazole N-oxides are easily accessible via heterocyclization reactions comprising condensation of α-hydroxyiminoketones 2 with formaldimines 3. The latter are known to exist

• dissolved in pyridine solution yielding the symmetrically substituted 1,3-dihydro-2H-imidazole-2-thione 17. Conclusion The present study demonstrates that the heterocyclization reaction with α-hydroxyiminoketones and formaldimines leading to 2-unsubstituted imidazole 3-oxides can efficiently be performed

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• preliminary results concerning the cancer selectivity of the selected agents. Results and Discussion Synthetic studies The steroidal β-ketoester precursor 4, suitable for the attempted heterocyclization reaction with hydrazines was synthesized from commercially available pregnenolone acetate (1) via a

• heterocyclization reactions were carried out with different substituted phenylhydrazine hydrochlorides 5d–j. All reactions furnished the corresponding 17-exo-heterocycles 6d–j in good to excellent yields (83–92%, Table 1). The electronic features of the substituents on the aromatic ring of 5 had a notable influence

• heterocyclization. In order to enlarge the compound library available for pharmacological studies, the 3β-OH analogs 7a–j of the primary products 6a–j were also synthesized through simple alkaline deacetylation (Scheme 2, Table 1). The structures of all synthesized compounds were characterized by 1H and 13C NMR

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• involve oxidation or reduction of related heterocycles (quinazolinones, quinazolines or tetrahydroquinazolines) [23][24][25][26][27][28]. Dihydroquinazolines can also be synthesized by heterocyclization of 2-aminobenzylamines (2-ABAs) with different C2 donors [3][16][17][29][30][31][32][33][34][35][36

• of PPA esters for the optimization of the heterocyclization reaction leading to compounds 1. Results and Discussion The synthetic strategy leading to DHQs 1 is depicted in Scheme 1. The key step of the sequence involves an N-arylation of 2-ABA with active haloaromatics (Scheme 2). As previously

• relatively longer reaction times than alkaneamides to achieve complete conversion at 120 °C. On the other hand, the reaction times were almost insensitive to the electronic features of the N-aryl group. This was quite unexpected in the context of the accepted mechanism for this heterocyclization, which

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

• to search for new reagents for the synthesis of their imidazo[1,5-b]-annelated analogues. There are two general approaches to the construction of an imidazo[1,5-b]pyridazine scaffold: the annulation of the imidazole ring to the b-bond of the pyridazine (route A, Scheme 1) and the heterocyclization of

• a result of their direct heterocyclization involving various single-carbon electrophilic reagents [15][16][20]. A similar one-pot aza-Staudinger reaction of 3-(azidomethyl)pyridazines with isothiocyanates in the presence of PMe3 also results in imidazopyridazines [17]. In the synthesis of imidazo

• methods the heterocyclization (method B) of 1-aminoimidazoles seems more attractive due to their better accessibility when compared to the corresponding pyridazines required in route A. Further, by careful selection of the reactants functional diversification of the target imidazopyridazines over