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

• generated nitrile oxide seems to be less significant. It was found that the low solubility of products containing aromatic substituents in non-polar solvents allows for their isolation by washing the crude reaction mixture with diethyl ether to remove organic impurities and then with water to eliminate

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

• further the applicability of the present synthetic method. Due to the excellent solvating power of CyreneTM, the “one-pot” synthesis of 1,2,3-triazoles could be proposed to eliminate the preparation and isolation steps of azide components. This could open an even greener and facile protocol for CuAAC

• demonstrated. The protocol was tested for a wide range of substrates, and successful synthesis and isolation of nineteen 1,2,3-triazole derivatives 3a–h, 5b–f, and 6a–f with moderate to excellent isolated yields (50–96%) and purity (>98%) was shown. Experimental The sources of chemicals are listed in

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

• CH2Cl2 led to isolation of a colorless, crystalline material with a narrow melting point of 107‒109 °C (yield 66%). The 1H NMR spectrum registered for the purified product perfectly fitted with that one of the crude mixture and thereby confirmed formation of a single product with a single set of the Me‒S

• selectivity, and in all cases formation of insertion products of both types, i. e., thioaminals 9 and dithioacetales 10, was observed (see Table 1). Chromatographic separation enabled the isolation of pure compounds, and the more stable dithioacetals 10 formed the more polar fraction. The less polar fraction

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

• dependence on the molar ratio of iodonium salt to isonitrile (Table 1, entries 14–21). In case of excess of the isonitrile we observed multiple addition and formation of oligomerized products which hindered the isolation of the product 2aa (Supporting Information File 1, 2.2 Preliminary and Additional

• conditions: 2-isocyano-1,3-dimethylbenzene (0.2 mmol), iodonium salt 1 (0.2 mmol), Na2CO3 (0.34 mmol), [Ru(bpy)3](PF6)2 (0.004 mmol), MeCN (2 mL), H2O (200 μL), under irradiation by blue LED (465 nm, 20 W) for 10 h. bDetermined by 1H NMR spectroscopy after isolation as a mixture of amides or a single amide

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• isolation of five phenolic siderophores with some of them exhibiting antimicrobial properties, including pseudomonins A–C and pseudomobactins A and B [15]. In this study we report the isolation and structural characterization of two previously undescribed as natural products (1 and 2) and two new compounds

• purification by a reversed-phase high pressure liquid chromatography (HPLC) system which led to the isolation of four compounds, trivially named pseudomonins D–G (1–4) and three known compounds 5–7 (Figure 1). Compound 1 was isolated as a yellow oil. The molecular formula C11H13NO5 (Δ: −0.7 ppm, 6 degrees of

• Compact Data Analyst (Bruker software) to provide accurate and high-resolution mass per charge of molecular ions in the sample and generate molecular formulae using a Bruker Smart Formula manually. Microbial isolation and identification The Pseudomonas sp. UIAU-6B strain was isolated from a sediment

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

• benefits, such as (i) improved reactions rates and yields in catalyst and solvent-free reactions, which enables easy isolation, and simplified work-up procedure; (ii) the neat reactions of the substrates eliminates solvents and thus reduces environmental and hazard impact; (iii) the HHP conditions enable

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

• E [30] and daphnepapytone C [31] from the 2020s (Figure 4). Most of these compounds possess intriguing biological activities and selected examples from this list are discussed in more detail in chapter 4 with regards to their isolation, bioactivity and a recent total synthesis. The aim of this work

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

• co-workers reported the oxidation of partially saturated precursor 23 using DDQ, which led to the isolation of PAH 24 in 50% yield which contains two formal azulene units (Scheme 4) [39]. However, compound 24 was found to possess a biradical structure (biradical character index, y0 = 0.49) with

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

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• , Supporting Information File 1), but it was not stable enough for isolation. The structure of 8a was confirmed by single crystal X-ray diffraction analysis. The optimized reaction conditions were used to evaluate the substrate scope of the synthesis of imidazopyridine-fused isoquinolinones 8 (Scheme 3). The

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• ). Reactions were set up in tandem and samples from both reaction vessels were taken, at 2, 4 and 6 h time points and used for TLC analysis to monitor reaction progress. The reactions proceeded in parallel, and both reactions had reached completion at 6 h. After isolation in high purity (≥95%) by silica flash

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• . Practical applications of this ability are directed to the selective isolation of gold from a variety of sources, spanning from gold-rich mining ores and tailings/mining wastes to gold-bearing metal scraps obtained from disposed electronic devices. Moreover, it describes the development of a method based on

• subsection, has sparkled the interest for industrial applications ranging from the recycling of gold-bearing e-waste [41] to the isolation of gold from mining sites. In 2014, a new company, Cycladex, was funded by Sir Fraser Stoddart and Dr. Roger Pettman with the mission of conducting eco-friendly mining of

• , there was the formation of the {α-CD·[K(OH2)6]+[AuBr4]−}n complex, leading to immediate precipitation. Isolation of metallic gold from the precipitate was achieved by addition of an organic reducing agent. Moreover, the study optimized the method to yield as much as 69% of gold from the original ore

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• difference in binding constants as well as the isolation of two distinct molecular conformations of phenylalanine HIM 1 (Figure 1), DFT calculations were performed. The details of DFT calculations are shown in Table 1. For DFT calculations, we assigned two HIM macrocycles per LiBArF20 as found in the co

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• well-established that it is featured in nearly every organic chemistry textbook. However, despite their versatility, enamines themselves are not easily handling compounds in experimental settings. Their sensitivity to hydrolysis complicates their isolation and identification, and following the

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• ). Giese addition using N-Cbz-Pro (12) and dimethyl maleate (13). Pinacol coupling of benzaldehyde (15). Supporting Information Supporting Information File 10: Reactivity studies, general experimental procedures, product isolation and characterization, spectroscopic data for new compounds, and copies of

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• Bansal and co-workers [44] revealed the potential formation of aza-QC derivatives at low temperatures. However, isolation of these derivatives proved difficult, as rapid rearrangement to azepine analogues occurred at temperatures exceeding 0 °C. On the basis of the quadricyclane or azepine structure

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• used it after isolation and characterization. In these cases, BINOL phosphate 5 was purchased, and used either without any further purification (Table 2, entries 5–7), or it was washed first with 2 N HCl solution, then rinsed with water, to remove possible traces of Ca2+, which could stem from

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• was obtained by a Migita–Kosugi–Stille coupling between bromophenanthrene 15 and (E)-1,2-bis(tributylstannyl)ethene to afford diarylethene 18 followed by Mallory photoreaction. The obtained intermediate 18 contained residual palladium and isolation was not successful due to its poor solubility in

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• configuration was determined by analyzing the 1H NMR spectrum in the δ = 2.8–1.7 ppm region, which displayed the characteristic diastereotopic hydrogen atoms of this compound, as previously reported by Biava et al. [15]. Unfortunately, the corresponding (2S,4S)-isomer 12b was intractable for isolation (yield

• the repertoire of published syntheses for this fluorinated derivative of natural leucine. Further attempts to the isolation of the second isomer will be made. Overall, this work further underlines the potential of chiral nickel complexes in synthesizing fluorinated amino acids. The diverse range of

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• -trans-cinnamoyl, these results suggested that massarilactone H could be an artifact formed during the extraction/isolation of massarilactone D. The molecular formula of compound 4 was deduced to be C38H32O9 from its HRESIMS spectrum (Figure S19, Supporting Information File 1) which showed the protonated

• with cinnamoyl chloride suggests that these two polyketides can interconvert from each other and could be artifacts and vice versa formed during extraction and isolation. This finding suggests that, to improve the antiproliferative efficacy of these derivatives, the exo-methylene group should be

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

• reactions [10]. Oxidation of the alcohol is done in situ to avoid problems regarding the isolation and instability of the aldehyde produced, although undesirable reactions, such as oxidation of the amines or isocyanides or overoxidation of the alcohol, could also be problematic [11][12]. In this regard

• well for a wide variety of solvents and under mild basic conditions, since the solubility of the reagents and ease of product isolation are the factors that govern the choice. Sisko et al. used DMF/K2CO3 as the best conditions to carry out the cycloaddition of a wide variety of amines, aldehydes, and

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

• isolation of intermediate salt 3a. Indeed, the reflux of starting compound 1a with amine 2a in AcOH for 24 h led to formation of product 4a with 62% yield. Using various furanones 1 and amines we attempted to synthesize analogues of compound 4a based on the above procedure. It was found that the presence of

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• isolation from cyanobacteria [2], their extraordinarily high cytotoxicity was apparent and attracted attention, not least because of their still high efficacy against multidrug-resistant (MDR) cells [3]. Cryptophycin-52, a synthetic development candidate by Eli Lilly based on the initially discovered

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• ANTH and the –C6F5 group might provide the desired spatial isolation of the ANTH (and other PAH) cores, and result in enhanced photoluminescence by disrupting close π–π stacking in the solid state. In addition, air- and photostability might also be improved due to the steric and electronic properties

• a relatively fast and efficient conversion into the desired products. Further optimization of this promising photochemical method is currently under way in our laboratory. Isolation and characterization Pure samples of 9,10-ANTH(BnF)2 and 9-ANTH(BnF) were isolated by HPLC (Figure S3, Supporting

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• yield (94%). The reaction remained efficient across a variety of substrates, as shown in Scheme 3. The authors noted that, if the mixture was not ground before irradiation, product 3.3 was obtained in just 46% yield after isolation. Thus, the role of mechanochemistry was to achieve optimal mixing of the

• ]. As an example, the authors were able to convert 4,4’-dimethoxybenzhydrol (6.1) to 4,4’-dimethoxybenzophenone (6.2) in 74% yield after isolation using 5 mol % RFTA under air (24 h), all performed without any additional solvent (Scheme 6). The authors noted that the reaction proceeds via a molten state

• oxidation of 1,2-diphenylethyne to benzil [71]. Thus, when a 1:2 mixture of 7.1 and 4-chlorothiophenol (7.2) was ground in the presence of eosin Y as the photocatalyst and anhydrous Na2SO4 as a bulking agent, benzil (7.3) was obtained in 43% GC yield under blue light irradiation (LED, 14.5 W). Isolation led