4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• , Vietnam Academy of Science and Technology (VAST), Hanoi 10072, Vietnam 10.3762/bjoc.21.65 Abstract Pyrrolidine-2,3-diones are important intermediates in the synthesis of numerous nitrogen-containing heterocycles which possess a broad spectrum of biological and pharmacological activities. In this article

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

• the cyclization process producing various highly diverse nitrogen-containing heterocycles, which are valuable scaffolds in medicinal chemistry [46]. Synthesis of non-aromatic heterocycles As stated above, DMSO can also hydrolytically decompose to formaldehyde. There are many examples of reactions in

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• significant attention for their unique photophysical characteristics and versatility in NIR-driven reactions [51]. Cyanins consist of nitrogen-containing heterocycles connected by a polymethin chain [52][53], whose synthesis and modifications have been widely explored [54][55][56]. Such compounds exhibit

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• . Review 1 Transformations via the formation of copper nitrenoids 1.1 C(sp3)–H amidation Lactams are recognized as one of the most significant nitrogen-containing heterocycles in drug discovery [69][70]. Among these, six-membered lactams, known as 2-piperidinones, have been extensively studied due to their

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

• afford 8b in 89% yield under similar conditions, in which the result of carbocyclic amide (7a vs 7b) contrasted with the case of heterocyclic ones, 1c vs 3 and 5a vs 5b. Conclusion We have shown the facile synthesis of fused nitrogen-containing heterocycles and extended the scope of the intramolecular

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

• imines; asymmetric organocatalysis; cyclization; N-heterocycles; inverse electron demand aza-Diels–Alder reaction; Introduction Nitrogen-containing heterocycles are abundant scaffolds present in natural products, biologically active compounds, pharmaceuticals, synthetic agrochemicals, and functional

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

• have identified effective modifications of peroxydisulfate-mediated oxidation reactions that allow us to obtain hydroxylated nitrogen-containing heterocycles in high yields. Our laboratory is currently investigating the application of these modifications to the oxidation of compounds of different

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• addition, the compatibility of the method with solid-phase synthesis is shown exemplarily. Keywords: azide; click reaction; CuAAC; pyrazole; triazene; triazole; Introduction Nitrogen-containing heterocycles are central scaffolds in medicinal chemistry and are incorporated in most small-molecule drugs [1

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• ][20][21][22][23][24][25][26][27], which can be readily generated in situ from α-halogeno hydrazones, have been extensively applied in recent years as versatile building blocks in inverse-electron-demand Diels–Alder (IEDDA) reactions [28][29][30] to construct diverse nitrogen-containing heterocycles

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

• reaction with neutral or anionic bases. Keywords: dipyrido[3,2-e:2′,3′-h]acenaphthene (acenaphthylene); hydrogen bonding; π-stacking; substitution reactions; tele-elimination; Introduction Quinoline derivatives, classical nitrogen-containing heterocycles, are widely distributed in nature in various forms

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• the ability to be readily transformed into various valuable functional molecules, including amines, hydrazines, and nitrogen-containing heterocycles [13]. In a significant advancement in 2021, Lopchuk et al. revealed a novel method for the photodecarboxylative alkylation of diazirines 12 using the

• ). Impressively, this transformation exhibited exceptional versatility, extending beyond coumarins to encompass other nitrogen-containing heterocycles, including quinoxalinones, with remarkable C-3 regioselectivity. The findings of this study significantly expanded the synthetic toolbox for accessing

• functionalized coumarin derivatives and related nitrogen-containing heterocycles, opening up exciting possibilities for their diverse applications in other fields. Similarly, the regioselective photodecarboxylative C–H alkylation of 2H-indazoles and azauracils using NaI/PPh3 as mediators and redox esters 3 was

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

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

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• unprecedented synthetic reactivity of the electron-deficient alkynes, but also provides efficient synthetic methodologies for complex nitrogen-containing heterocycles. The potential application of this reaction in organic synthesis and medicinal chemistry might be significant. Experimental General procedure for

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -containing heterocycles intensively studied in medicinal chemistry and pharmacology. In the present paper, a new synthetic approach to pyrrolobenzothiazoles is developed based on 1,4-thiazine ring contraction in 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones under the action of nucleophiles. The

• Ekaterina A. Lystsova Maksim V. Dmitriev Andrey N. Maslivets Ekaterina E. Khramtsova Department of Chemistry, Perm State University, ul. Bukireva 15, Perm 614990, Russian Federation 10.3762/bjoc.19.46 Abstract Pyrrolo[2,1-b][1,3]benzothiazoles are an important class of fused sulfur and nitrogen

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• ; pyrrolothiazoles; spirooxindole; Introduction Nitrogen-containing heterocycles play a dominant role as a structural fragment of therapeutic agents in medicinal chemistry and drug discovery [1][2][3][4][5][6][7][8][9]. The nitrogen-containing heterocyclic moieties are currently discovered in more than 75% of the

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• -azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate with Zn/NH4Cl and debenzylation resulted in the target aziridinecyclooctanediol. Keywords: aminocyclitols; aminocyclooctanetriol; azides; aziridines; aziridinecyclooctanediol; Introduction Aziridines are the smallest nitrogen-containing heterocycles

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• a 3-pyrroline-2-one skeleton could be promising drug candidates. Therefore, these nitrogen-containing heterocycles have attracted attention and they have been investigated most intensively via multicomponent reactions (MCRs). This kind of reaction has been proven to be an efficient synthetic pathway

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• of nitrogen-containing heterocycles in the fluorescent materials, the addition of a Lewis acid tended to induce red-shifted absorption and emission, shedding light on the fact that the Lewis acid interacts easily with the nitrogen-containing fluorescent materials. This interaction mechanism is the

• nitrogen-containing heterocycles, resulting in the change of energy levels and spectra. The following will illustrate Lewis acids used in the exploration of luminescent materials and mechanisms due to Lewis acid–base interactions. The chemical structures of some candidate Lewis acids are shown in Figure 1

• , it is essential to explore the mechanisms. Welch et al. supposed that the strong electrophilic Lewis acid triggers charge transfer with nitrogen-containing heterocycles containing lone-pair electrons. Consequently, it reduces the electron density of the π-conjugated system and the characteristics of

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• direct C–H amination is vital to provide many amine derivatives by sustainable methods [36][37]. The dehydrogenative C–N cross-coupling reactions from unreactive N–H and C–H bonds can lead to various nitrogen-containing heterocycles [32][38]. Herein, we disclose the DDQ-mediated oxidative C–N coupling

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• 166 which is oxidized by Fe(III) to a carbocation species 167. Subsequent attack by the nitrile affords the nitrilium ion 168 which upon hydrolysis gives the final product 164. Oxime esters and ethers represent a widely used starting material for the generation of nitrogen-containing heterocycles. Due

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

• nitrogen atom to nitrenium intermediates occurred initially; further stabilization of these species resulted in the formation of hydroxylated lactams [44][45][46][47][48], azaspirocycles [49][50][51][52][53], or tricyclic nitrogen-containing heterocycles [44][53]. Our study commenced with the synthesis of

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• ] and procuramine (10) [13], have also attracted attention recently. Our continuing efforts to exploit enaminones as building blocks for the synthesis of alkaloids and other nitrogen-containing heterocycles have largely concentrated on targets containing indolizidine and quinolizidine backbones [14

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• reaction and sequential aromatization process. Keywords: carbazole; chalcone; Diels–Alder reaction; maleimide; pyrrolo[3,4-c]carbazole; 3-vinylindole; Introduction Carbazole is one of the most well-known privileged nitrogen-containing heterocycles. The carbazole skeleton is widely occurring in natural

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• this compounds are required. In this regard we suggested the modification of the alcohol tail of metronidazole by incorporating an N-heterocyclic moiety. Nitrogen-containing heterocycles play a vital role in agrochemicals and pharmaceuticals [3]. Among these heterocyclic systems, the 1H-1,2,3-triazoles

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

• , respectively (Table 2, entry 3). Apart from the 1H-indazole scaffold [36][37], the steric influence of adjacent substituent(s) on N-alkylation regioselectivity has previously been described for other nitrogen-containing heterocycles, such as pyrazole [38], purine, and related 1,3-azoles [39]. Although the N

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

• in 57% yield (1:1 dr, Scheme 18C). Nitrogen-containing heterocycles are present in several valuable bioactive compounds, such as piracetam (50) [132], anisomycin (51) [133], and alogliptin (52) [134] (Scheme 20A). Sometimes better biological results are observed after simple structural modifications