3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• shorter heptaethylene glycol macroycle Me-M17. The synthesis of the octaethyleneglycol derivative Me-M18 was repeated several times but gave reproducibly lower yields than the shorter version Me-M17. All macrocycles were fully characterized by standard analytical methods (see Supporting Information File 1

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• process [12][13][14][15]. Extensive case studies in the literature reveal that flow chemistry offers notable advantages over traditional batch methods. The intrinsic safety advantage of flow systems stems from the dramatically smaller reaction volume and larger specific surface area compared to batch

• -flow nitration innovatively reimagines conventional methods for managing exothermic and selectivity-sensitive reactions, systematically analyzing four distinct approaches (nitration with mixed acids; nitration with fuming nitric acid; vapor-phase nitration; nitration with solid acid catalysts) to

• including but not limited to exothermicity profiles, intrinsic reaction rates, and phase behavior. The quenching zone of a continuous-flow nitration system can achieve termination of the nitration reaction through dilution, reaction, and other methods. Without a reasonable quenching method, it is difficult

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• biomolecules in organisms. However, the R/S stereochemistry of pyruvate ketal is difficult to control through chemical methods. In this study, the acid-labile pyruvate ketal linked to the 4- and 6-positions of galactose was cautiously constructed, and the X-ray analysis of the R-configured product was

• promising regio- and stereoselectivity. Detailed characterization using NMR and X-ray methods clarified the diastereoselective structure of the pyruvate ketals, enabling the successful synthesis of oligosaccharides containing pyruvate ketal groups. Pyruvylated galactose on bacterial polysaccharides PS A1 (1

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• attention due to its broad applications in various fields, including but not limited to drug discovery, asymmetric catalysis, and materials science (Figure 1b). Consequently, the development of efficient and stereoselective methods for assembling such scaffolds with respect to structural diversity has

• these notable accomplishments, this research field remains in its nascent stage with ample room for further exploration. First, existing studies have predominantly focused on the construction of axial chirality, while synthetic methods for other forms of non-central chirality, such as planar, helical

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• have begun studying reactions that combine the advantages of photochemical methods and mechanochemistry. This thematic issue contains a Perspective article from the Capaldo laboratory that surveys these efforts and discusses future possibilities [38]. Without a doubt, the growing interest in light

• -mediated organic synthesis has also resulted in a renaissance of radical chemistry. Once regarded as “[…] messy, unpredictable, unpromising and essentially mysterious” [39], radical-based methods have become central to modern organic chemistry, spanning applications in the life sciences. The Perspective

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• functionals being quite similar among them. Therefore, we concluded that M06-2X, whose calculated geometry is almost coincident with that computed with B3LYP-D3BJ, is the most precise functional to predict the two-color behavior of these fluorescent sensors. Computational Methods All the DFT [32] and TDDFT

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• aromatic character in their transition states, this increased aromaticity does not necessarily correlate with lower activation barriers. State-of-the-art computational methods on reactivity, such as the combined activation strain model (ASM)–energy decomposition analysis (EDA) method, reveal that factors

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• S1 states of (A) (Sp)-6 and (B) (Sp)-7 (TD-MN15/6-31G(d)). Synthesis of cyclic dimer (Sp)-6 and trimer (Sp)-7. Supporting Information Supporting Information File 26: Statement of computational methods, NMR and HRMS spectra, PL decay curves, glum charts, calculated ECD spectra, and cartesian

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• reactions of heteroaromatics with azirines are known only for 2-chloro- and 2-sulfanylpyridines [14][15], which result in the formation of imidazo[1,2-a]pyridines (Scheme 1, reactions 4 and 5). To the best of our knowledge, no successful methods enabling the fusion of a pyrrole or azole ring to a 5-membered

• ester group. In our case, the demethoxycarbonylative annulation enables the formation of aromatic tricyclic benzo[4,5]thieno[3,2-b]pyrrole system which is encountered in compounds with antitumor activity [21][22] as well as in compounds exhibiting fluorescent properties [22][23]. Since general methods

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• determined by the configuration of the spiro-core, while still allowing for the possibility of relative rotation to facilitate better binding to the targets. Furthermore, it appears to be as exceedingly advantageous from a synthesis perspective, as it enables the application of methods that have been

• regioselectively for both methods. In most cases, the reactions proceeded with high yield and without the formation of significant byproducts. Results and Discussion Synthesis Hydantoins 2, containing an exocyclic C=N group, were synthesized according to the methodology described in [22] (Scheme 1). In brief, N,N

• reactions with nitrile oxides. The nitrile oxide precursors, hydroxyimidoyl chlorides 4a–d were prepared according to known methods [23][24] (Scheme 2). Conversion of benzaldehydes to the corresponding benzaldoximes 3a–c was achieved through a reaction with hydroxylamine hydrochloride and a base. The dipole

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• methods, the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, the so-called click reaction [7], has received substantial attention for the selective synthesis of various 1,2,3-triazoles that are of utmost importance in the synthesis of biologically active compounds such as active

• for 4 consecutive runs, which resulted in high conversion of 1a in each run (Figure 6). To evaluate and compare the one-pot protocol with published methods, the environmental factor (E-factor) was calculated for the synthesis of 3a. Considering an average 88% solvent recovery, the E-factor is 76. It

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• condensation of 1,3-dicarbonyl compounds with amines [30]. While this approach is simple and straightforward, it often leads to a mixture of constitutional isomers in which the two different α-positions of the ketone have been functionalized. Therefore, the development of novel methods for the synthesis of

• presence of amines and CuI as catalyst, as reported by Zhang and co-workers (Scheme 1B) [32]. On the other hand, Li et al. disclosed a silver-catalyzed amination of propargyl alcohols to afford enaminones (Scheme 1C) [33]. Although these new methods provide a wide variety of enaminones, there are

• limitations such as expensive and unavailable reagents, long reaction times and drastic reaction conditions. Furthermore, the increasing emphasis on economic and environmental factors has highlighted the limitations of traditional methods for enaminone synthesis to align with the modern understanding of

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• for esters requires the development of scalable production methods. Heterogeneous CaO-based catalysts for the production of esters by transesterification are promising catalytic systems for the production of these desired compounds. In this work, the application of calcium carbide slag, a byproduct of

• [31][32][33][34], and cosmetic industries [16][17][35][36]. Fatty acid methyl esters (biodiesel) are of particular interest due to their current use as fuel in vehicles and promising applications [37][38][39][40][41][42][43]. The esters are demanded in large amounts according to available methods for

• industrial wastes not only contributes to reducing environmental impact, but also provides new opportunities for the development of sustainable synthetic methods in the chemical industry. Further research can be focused on optimizing the process and exploring the applicability of this catalyst in other

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• of the most important types of organic reactions with key importance for the development of methods of modern organic synthesis [1][2][3]. Therefore, conversions of 1,3-dipoles which cover not only cycloadditions but also annulation and insertion reaction attract great attention worldwide [2][3][4

• ]. Thiocarbonyl S-methanides (thiocarbonyl ylides) 1, which were first reported in the 1980s by R. Huisgen and co-workers contributed to a substantial extension of mechanistic interpretations of cycloaddition reactions and to rapid development of methods applied not only for the synthesis of sulfur heterocycles

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• activity than cotylenin A in cell growth inhibition assays and less toxicity in single-agent treatments [27][28]. Recently, Jiang and Renata described a chemoenzymatic approach that combines the skeletal construction by chemical methods and enzymatic C–H oxidations [29]. The synthesis employs a catalytic

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• [20][21]. However, diazonium salts are distinguished by their inherent instability complicating their use in such transformations. Moreover, among the various arylation strategies, photochemical methods remain relatively underexplored, with only a few examples reported [22][23]. These methods often

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• , and the huge overall economic impact of these processes. Inspired by the logic behind cross-dehydrogenative C–C-coupling methods [15], the direct C–H amination has been developed as a more straightforward, economical and environmentally friendly reaction, compared to its counterparts (such as the

• methods are simple, inexpensive and scalable, making the catalyst reliable and suitable for large scale production. This study aims to optimise an efficient, user-friendly and heterogeneously catalysed procedure that enables the rapid synthesis of 2-aminobenzoxazole derivatives. A key focus is leveraging

• improvements made using conventional methods, we tested the reaction under MW irradiation (see Table 2). Two different pieces of equipment were evaluated: a flexible MW oven (Microsynth by Milestone) for traditional glassware synthesis and a MW reactor (SynthWave by Milestone) capable of handling any reaction

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• problem pending solution. Conclusion Two novel azo dyes originating from 7-hydroxyquinoline have been synthesized and studied by a variety of experimental and theoretical methods. It has been shown that 8-(phenyldiazenyl)quinolin-7-ol exists in solution as an equilibrium mixture of three different

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• ]. These data [1][2][3][4][5] inspired researchers to expand the chemistry of these compounds and to search for new synthetic methods and chemical transformations [14][15]. Unlike the aromatic congeners, the chemistry of non-aromatic dihydro-1,2-thiazoles is less represented in the literature [16][17][18

• was synthesized. Experimental Thioamides 1a,f,g,l,r [19], 1b,c,d,e,j,u,x [20] and iodonium salts 2a [21] and 2f [22] were synthesized according to the previously described methods. The structures of all thioamides used in this study are provided in Supporting Information File 1. Preparation of

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• -products. A computational study accompanies the experimental data to interpret the outcome of the reactions. Keywords: acetaminophen; acetylsalicylic acid; benzimidazoles; catalyst-free synthesis; cyclization; esters; high hydrostatic pressure; pyrazoles; Introduction Non-traditional activation methods

• are one of the major driving forces in green synthesis [1][2]. High hydrostatic pressure (HHP) activation, one of such methods, is based on mechanical compression force. The typical pressure range is 2–20 kbar that is orders of magnitude greater than the conditions traditionally employed in chemistry

• protocol was even applied in the elegant syntheses of platencin [30], and steroid derivatives [31]. Despite these encouraging applications, there is a broad area to be developed for the advancement of green synthesis efforts. Continuing our program on developing environmentally benign synthetic methods [32

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• methods for oxetane synthesis, mainly due to its practicality and versatility. 1.1.1.1 Substitution of a leaving group: In 2017, Moody et al. developed a new route towards spiro-oxetanes 8 utilising a combination of 1,4-C–H insertion and Williamson etherification (Scheme 3) [38]. The methodology commences

• derivatisation methods have been developed – these expand not only the scope of synthetic strategies towards known oxetane building blocks, but also the library of medicinally relevant oxetane derivatives. This chapter summarises the recent functionalisations of 3-substituted oxetanes whose synthesis can be

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• modified. In recent years, photocatalysis has been widely adopted due to its green and efficient nature [45][46][47][48][49][50][51]. The generation of amidyl radical is implemented by HRP. Six different methods (Figure 2c), which have been developed for visible-light mediated reactions, could generate

• insight in the development of novel methods for amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer. Although, amidyl radicals employed in many reactions as HAT reagents via heating conditions have been summarized in several studies [52][53][54][55][56][57][58]. To advance

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• ], medicine [3], sensing [4] and energy storage [5]. Typically, bulk graphene is obtained using a top-down approach, where graphite is exfoliated using chemical or mechanical methods [6][7]. However, this method does not provide precise control over the structure of graphene and graphenoid materials, which is

• ]indene (6) as black plates in a 32% yield. The azulene-containing isomers of pyrene exhibit azulene-like absorption tailing up to around 650 nm. Interestingly, despite their initial synthesis in the 1950s, no further attempts have been made to synthesize compounds 2 and 6 using more modern methods

• = 1010 nm, which is a strong indicator of its dominant non-alternant character. Traditional methods for synthesizing azulene-embedded PAHs often require harsh conditions, making them challenging to apply to larger π-scaffolds. Furthermore, these methods frequently suffer from low yields and are not

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• rapid construction of complex molecular architectures. This review aims to summarize the diverse strategies for inducing intramolecular transformations of N-arylacrylamides using various carbon radical reagents, including methods initiated by photonic, thermal, or electrochemical processes, which have

• methods utilizing electron donor–acceptor (EDA) complexes and peroxide initiators have recently gained attention due to their operational simplicity and environmental friendliness. In 2024, Song’s group and co-workers presented a novel metal-free, visible-light-promoted method for synthesizing

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• -inflammatory [21][22] as well as enzyme inhibition activities [23][24][25][26]. Traditionally, β-ketophosphonates were prepared via Arbuzov reaction [27], acylation of alkylphosphonates [28], and hydration of alkynylphosphonates [29][30][31]. However, these methods have several drawbacks, including low atom

• ], etc.) and strong oxidants (K2S2O8 [46][54], Mn(OAc)3 [56][57], organic peroxides [51][58][59], etc.) are employed in these approaches. Modern photocatalytic [47][50][60][61] and electrochemical [48][62] methods were also recently reported. Although several successful oxyphosphorylation reactions