Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• . Keywords: alkynes; catalysis; cyclizations; domino reactions; heterocycles; Introduction Pyrimidines and purines are one of the most important heterocyclic compounds with prevalent biological functions. Both are found in nucleosides and their corresponding polymeric DNA and RNA, and hence are vital for

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• catalytic efficiency (up to 99% yield). Keywords: chitosan-supported CuI catalyst; cyclization reaction; mild conditions; quinazolinone; Introduction Quinazolinones are not only a key core of nitrogen-containing benzo heterocyclic compounds found in many natural products and bioactive molecules [1][2][3

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• have a low oxidation potential and can be oxidized quickly to act as a catalyst (Scheme 5). Acridines are important nitrogen-containing heterocyclic compounds used as the building block for preparing medicinally active compounds. The conjunction of phosphorus with acridine increases its biological

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• . Synthesis of heteroaromatic systems One of the most powerful applications of MCRs is the synthesis of heterocyclic compounds and several reports in recent years showed the advantages of using this tool as a synthetic strategy to generate complex molecular scaffolds with medicinal relevance [25][26][27]. In

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• unambiguously confirmed by X-ray diffraction. Keywords: allomaltol; enamines; 2H-furo[3,2-b]pyran-2-ones; pyrazol-3-ones; recyclization; Introduction Substituted furan-2(5H)-ones (butenolides) are widely used as precursors for the preparation of diverse types of heterocyclic compounds possessing various

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• ; Introduction Pyrazoles and 1,2-diazoles are five-membered aromatic heterocyclic compounds that have garnered significant attention in recent years [1][2][3]. While these compounds are rarely found in nature, they exhibit a wide range of biological activities, making them highly useful in pharmaceutical

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• 2-(indolin-2-yl)-1,3-tropolones [5]. Unlike the cross-aldol reaction of o-chloranil with methyl ketones [13][14][15], which is always accompanied by the removal of one of the chlorine atoms from the seven-membered ring, the acid-catalyzed reaction between methylene-active heterocyclic compounds and

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• Klebe’s research group in 2007 [40]. A literature survey revealed that various heterocyclic compounds especially benzenesulfonamides can be best CAIs [41][42][43]. These CAIs are used to treat different pathological conditions like epilepsy [44], glaucoma [45], diabesity [46], obesity [47], neuropathic

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

• heterocyclic structures leads to the production of new types of heterocyclic compounds with practical useful properties [1][2][3][4][5][6]. Representatives of the naphthofuran series exhibit anticancer [7] and antiinfectious activity [8]. Anticancer properties have also been found in representatives of the

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• disulfides from sodium sulfinate without the use of additional redox reagents remains a challenging task. 3-Sulfenylchromones are an important class of heterocyclic compounds with unique skeletons in nature that play an essential role in drug synthesis and development. To synthesize these compounds, direct C

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• transition-metal catalysts provides synthetic tools even more advantageously. Copper has also become very interesting in this field, mainly in processes aimed at synthesizing heterocyclic compounds. Among the various catalysts, Cu(OTf)2 stands out in heterocyclic synthesis and ring transformations due to its

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• % yield, respectively. The related reaction is also carried out with amides of non-pyridine derivatives terephthal- and benzamides to afford multiply fused heterocyclic compounds in 81% and 89% yields, respectively. Keywords: intramolecular C–H arylation; multiply fused heterocycles; palladium acetate

• [30][31][32]. We herein report the palladium-catalyzed intramolecular C–H arylation of several pyridine and non-pyridine amides to afford multiply fused heterocyclic compounds. Results and Discussion First, we started with the synthesis of the cyclization precursors 1a–c that was carried out by the

• , 126.3, 123.8, 122.7, 118.3, 115.4, 43.3, 31.9, 29.5, 29.3, 27.3, 27.1, 22.7, 14.2; IR (ATR): 2959, 2929, 2856, 1661, 751 cm−1; HRMS–DART+ (m/z): [M + H]+ calcd for C24H27N2O, 359.2123; found, 359.2134. Structures of multiply fused heterocyclic compounds composed of pyridine rings. Synthesis of C–H

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• construction of carbon–carbon bonds [5][6][7][8][9][10]. The hetero-Diels–Alder reaction is therefore an attractive strategy for the synthesis of heterocyclic compounds. It involves the reaction of dienes or dienophiles which possess a heteroatom in their structure. In this reaction, the HOMO of the diene and

• dienophile, and therefore it proceeds through the reaction of electron-poor dienes and electron-rich dienophiles (Figure 2b). α,β-Unsaturated imines can undergo inverse electron demand aza-Diels–Alder reactions (IEDADA) to produce N-heterocyclic compounds. The search for an enantioselective pathway to carry

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• synthesizing diverse scaffolds [6]. Furthermore, the Ugi reaction exhibits versatility in forming both fused and unfused heterocyclic compounds, involving 4-, 5-, 6-, and 7-membered rings [17]. This capability is exploited by various approaches, including the Ugi–Deprotection–Cyclization strategy (UDC) and

• -Ugi transformations, it is possible to obtain diverse heterocyclic compounds with tetrazole moieties [65]. In this context, Medda et al. [66] developed a three-step process to access biologically active imidazotetrazolodiazepinones. The first one is the AU-4CRs among ethyl glyoxalate, amines

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• ; heterocycles; hypervalent iodine; oxidation; Introduction Halogenated carbocyclic and heterocyclic compounds are present in many active pharmaceutical ingredients [1][2]. The intramolecular halocyclisation of alkenes mediated by HVI(III) reagents allow access to a range of halogenated cyclic scaffolds in a

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• olefins and isocyanides (Scheme 4). As expected, under almost the same conditions as described in Scheme 3 (only at 80 °C), a new type of heterocyclic compounds, pyrrole-fused triazolobenzodiazepines, was obtained in high yield. As summarized in Scheme 4, a variety of gem-diactivated olefins with electron

• great attention in biomedical applications, clinical diagnostics, and conjugate materials. Keywords: cyclic imines; dibenzothiazepine; dibenzoxazepine; isocyanides; multicomponent reactions; pyrrole; triazolobenzodiazepine; Introduction Pyrroles and their derivatives are important N-heterocyclic

• compounds with antibiotic, antiviral, and anticancer properties that are found in many drugs and natural products [1][2][3][4][5][6]. Pyrroles' biological properties manifest when they are fused to other heterocycles [7][8][9][10][11][12]. Among them, seven-membered heterocycles of the benzodiazepine

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• -acylamine; oxazole; propargylamine; Introduction Propargylamine is an important motif in the synthesis of heterocyclic compounds [1][2][3][4] and drug discovery [5][6] due to its multifunctionality, which includes a basic and nucleophilic amino group, an electrophilic and dipolarophilic triple bond, and an

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• in clinical use, suggest that they may possess antifungal activity against Candida albicans. Keywords: 2-aminoimidazole; antimycotic activity; imidazo[1,2-a]pyrimidine; molecular docking; N-arylitaconimides; N-substituted maleimides; recyclization; Introduction Nitrogen-containing heterocyclic

• compounds occupy a pivotal position in the arsenal of modern organic and medicinal chemistry due to their extensive spectrum of physiological activity [1]. Imidazo[1,2-a]pyrimidines represent one of the most promising classes of compounds within this group [2][3]. These small azoheterocyclic frameworks

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• Alfiya R. Gimadieva Yuliya Z. Khazimullina Aigiza A. Gilimkhanova Akhat G. Mustafin Ufa Institute of Chemistry at Ufa Federal Research Center, Russian Academy of Sciences, 71 prosp. Oktyabrya, 450054 Ufa, Russian Federation 10.3762/bjoc.20.219 Abstract Nitrogen-containing heterocyclic compounds

• convenience of the process, our objective is to enhance the efficiency of the Elbs and Boyland–Sims peroxydisulfate oxidation reactions. Results and Discussion We conducted research to enhance the product yield of peroxydisulfate oxidation reactions of specific nitrogen-containing heterocyclic compounds, such

• oxidation of nitrogen-containing heterocyclic compounds can be enhanced by the introduction of phthalocyanine catalysts or hydrogen peroxide into the reaction mixture. This approach has the potential to significantly increase the yield of the target compounds. Conclusion In conclusion, it is noted that we

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• ; 1,1′-carbonyldiimidazole; 3-hydroxypyran-4-ones; tetronic acid; Introduction 3-Hydroxypyran-4-one derivatives are an important class of heterocyclic compounds widely represented in various naturally occurring sources [1][2][3][4]. Products of this type demonstrate a broad range of biological activity

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• derivatives bearing both aromatic and aliphatic substituents. The NO-donor ability of the synthesized furoxano[3,4-d][1,2,3]triazin-7(6H)-ones was additionally evaluated. The elaborated method provides access to novel nitrogen heterocyclic compounds with potential applications as drug candidates or

• high-energy materials [8][9][10][11][12][13]. Moreover, furazan derivatives possess antiproliferative, antibacterial, antiparasitic and antiviral activity [14][15][16]. On the other hand, furoxans referred to as unique heterocyclic compounds that exhibit NO-releasing properties under physiological

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• solution, as described in the experimental section. This information is provided in brackets. Review Synthesis of azacycles Nitrogen-containing heterocyclic compounds possess numerous applications in various domains such as materials science, agrochemistry and medicinal chemistry. Especially, 60% of all

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• purification. Thus, it significantly improves existing approaches. Keywords: catalysis; deazaalloxazine; flavin; multicomponent approach; one-pot reaction; Introduction Heterocyclic compounds containing pyrimidine and quinoline motifs in their structure, both of natural and synthetic origin, find a wide set

• mechanism, see Supporting Information File 1). Such results with previous reports on DMSO acting as a methine source in the synthesis of heterocyclic compounds [35][36] are opening a new avenue for the green synthesis of non-substituted 5-deazaalloxazines in a pseudo MCR fashion. Conclusion In summary, we

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• Ukraine "Directed synthesis, chemical transformations and properties of new nitrogen-containing heterocyclic compounds" (0122U001857).

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• generated by addition reaction of isocyanides to electron-deficient alkynes, which were sequentially trapped by various electrophiles and nucleophiles to give versatile acyclic and heterocyclic compounds [15][16][17][18][19][20][21][22][23][24][25][26]. In recent years, many multicomponent reactions based

• on alkyl isocyanides, electron-deficient alkynes and other reagents have been successfully developed for the synthesis of various carbocyclic and heterocyclic compounds [27][28][29][30][31][32][33][34][35]. The 5,6-unsubstituted 1,4-dihydropyridine is one of special kinds of 1,4-dihydropyridines. It

• synthetic protocols and in continuation of our aim to develop isocyanide-based multicomponent reactions for construction of diverse nitrogen-containing heterocyclic compounds [47][48][49][50][51][52][53][54][55][56][57][58], herein we wish to report the mutlicomponent reaction of alkyl isocyanides, dialkyl