Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• and were used without further purification. H2 was synthesized according to a previously published procedure [39]. NMR spectra were measured on commercial spectrophotometers at 400 MHz for 1H and 100 MHz for 13C in trifluoroacetic acid with a capillary tube containing deuterated water (D2O) for

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• the volatility of 13, the crude solution obtained after the workup (quenching and phase separation) was directly used in the subsequent reaction without purification. Esterification of (2S,3S)-13 with p-nitrobenzoyl chloride (PNBCl) afforded PNB ester (2S,3S)-8 in 45% yield for two steps

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• avoiding excess reagent, and simplifies purification and scale-up. With the most suitable reaction conditions in hand, the substrate scope was examined. First, the reactivity of different aryl bromides with phenylhydrazine (1a) to form non-symmetric azobenzene was explored (Scheme 1). Most of the

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• KGaA, Darmstadt, Germany), adjusting the pH with HCl. Water for buffer and eluent preparation were provided by a Millipore Milli-Q water purification system. Kinetic aqueous solubility assay. All compounds were dissolved in DMSO to make stock solutions at 10 mM concentration. In the case of 7i, 7j, and

• to LC–MS). Pure (E)-7h was obtained by purification using flash chromatography (hexane–EtOAc). Yield: 45 mg (40%), colorless crystals. Mp 138–139 °C (EtOH); 1H NMR (600 MHz, DMSO-d6) δ 9.54 (br s, 1H), 7.80 (d, J = 8.6 Hz, 1H), 7.62 (m, 2H), 7.57 (m, 2H), 7.54 (m, 3H), 6.71 (d, J = 7.7 Hz, 1H), 3.47

• ). Pure (Z)-7h was obtained by purification using flash chromatography (hexane–EtOAc). Yield: 17 mg (15%), pale yellow crystals. Mp 145–146 °C (EtOH); 1H NMR (600 MHz, DMSO-d6) δ 9.38 (br s, 1H), 7.84 (d, J = 8.5 Hz, 1H), 7.69 (m, 1H), 7.59 (m, 2H), 7.55 (m, 3H), 6.81 (d, J = 7.7 Hz, 1H), 6.77 (t, J = 5.2

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• used without further purification. Melting points were obtained with a Mel-Temp capillary apparatus and were not corrected. IR spectra were obtained as KBr disks on a JASCO FT/IR-410 spectrophotometer. The FAB mass spectra were recorded using a JEOL 600H mass spectrometer. 1H and 13C{1H} NMR spectra

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• . After evaporation of the solvent MeOH, the residue was redissolved in 2 mL of MeCN and heated at 130 °C for 2 h in a sealed vial to give product 7a in 90% yield after purification via Cu-free intramolecular click reaction (Scheme 3C) [46]. This Cu-free intramolecular cyclization provides key practical

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• intermediate purification, work-up, or solvent exchange. Domino processes [3] are characterized by the simultaneous presence of all reactants from the outset, whereas sequential reactions permit the controlled addition of components while maintaining the same reaction conditions. Consecutive processes, in turn

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• further purification after filtration. The use of starting components containing highly reactive groups, for example, an azide group, in the Ugi reaction provides opportunities for various post-cyclizations to obtain nitrogen-containing heterocyclic systems with potential biological activity [18]. To

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• higher reduction potential of this comparatively electron-rich compound. Purification of the crude reaction mixture from 1 by column chromatography allowed for the isolation of pure product 5 as a colorless oil in 59% yield. A control reaction performed under the same conditions in the dark resulted only

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• diverse co-substrates. A high-throughput approach was used to identify promising substrate/co-substrate/catalyst combinations which were then prioritised for purification by mass-directed HPLC to yield a total of thirty reactive probes. The structural diversity of the probe set was increased by the

• reactions, a product with molecular weight consistent with O–H insertion into water was also observed. For these 18 substrate/co-substrate combinations, the reaction with the highest estimated yield was selected for mass-directed purification (Table 2). In total, 23 intermolecular reaction products were

• tag (C17 and C18) were used. The reactions were assembled from stock solutions, with some variation in stock concentrations to improve solubility. After 24 h, the reaction products were analysed by LC–MS, and promising reactions selected for mass-directed purification. Seven additional intermolecular

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• (O)Cl3 and glycidol were purchased from suppliers and used without additional purification. Synthesis of diglycidyl methylphosphonate (1). A 500 mL flask with 200 mL of dichloromethane, equipped with a mechanical stirrer, was cooled to −30 °C. Then, 2 equiv of glycidol (21.4 g, 0.289 mol) and 4.2

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• bridged azabicyclic ring system found in alstonoxine A and related alkaloids. Experimental Chemicals described were obtained from commercial suppliers and were used without further purification. Solvents were obtained from a Grubbs dry solvent system. Thin-layer chromatography was performed on Merck

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• MeOH with acetic acid as an additive. This is a step toward the large scale synthesis of enantioenriched vinyloxazolines 6 from biomass-derived furfural, however, several challenges remain such as replacing LiClO4 as electrolyte at the oxidation step and avoiding chromatography for purification

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• nitrogen source followed by thin-layer chromatography and reversed-phase (RP)-HPLC to isolate and purify the compound from a complex mixture of indole alkaloids [11], (ii) prepared by aerobic incubation of indole-3-pyruvic acid at pH 7.4, 37 °C for 24 h followed by isolation and purification using RP-HPLC

• easier purification. The N-Boc-protected indole-3-acetic acid was subsequently treated with N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC) [29] in the presence of DMAP to generate the N,N′-Boc-protected malassezione (23). Use of EDC greatly facilitated the purification since the resulting urea

• derivative was easily removed with aqueous washes, thereby obviating the need for column purification to remove the more hydrophobic dicyclohexylurea obtained when DCC was employed to facilitate the reaction. Subsequent removal of the Boc groups with TFA furnished malassezione (1) in an overall yield of ca

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

• with CHCl3 as a solvent at room temperature. Circularly polarized luminescence (CPL) spectra were recorded on a JASCO CPL-300 with CHCl3 as a solvent at room temperature. Materials Commercially available compounds used without purification are as follows: Pd2(dba)3, SPhos (2-dicyclohexylphosphino-2',6

• , respectively. Dimer (Sp)-6 (6.8 mg, 0.0062 mmol, 16%) was isolated from the first fraction by recyclable HPLC (CH2Cl2 as an eluent) as a light yellow solid. Trimer (Sp)-7 was isolated from the second fraction by recyclable HPLC (CH2Cl2 as an eluent). Further purification of (Sp)-7 was carried out using chiral

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• comparison with previous, traditional, and time-consuming synthesis of PI-88 glycan components, the one-pot glycan assembly strategy has some advantages, including: 1) acceleration of glycan synthesis, 2) avoidance of purification of intermediates during glycosylation intervals, and 3) reduction of chemical

• all Bz groups with 1 M NaOH (dioxane/MeOH/H2O, room temperature). The monophosphorylated trisaccharide 1 was obtained in 60% overall yield over two steps from 12 after purification over a SephadexTM LH-20 column. It was noted that the switch of deprotection sequences (first Bz groups, second Bn and

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• -catalyzed cross-coupling reactions between bromo-substituted perylene or phenothiazine precursors and appropriate donor or linker units, followed by purification via column chromatography and gel permeation chromatography (Figures S18–S21 in Supporting Information File 1). The details of the syntheses are

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

• cycloaddition (32CA) of nitrile oxides with 5-iminohydantoins (Figure 1). The proposed method involves the use of readily available starting materials, avoids chromatographic purification of the final products which are obtained in good yields. We have also tested the cytotoxicity of some synthesized spiro

• triethylamine hydrochloride. This method has proven to be simple and effective in most cases, with the exception of compound 5g. The moderate solubility of this compound in diethyl ether led to partial precipitation from the reaction mixture. It is worth noting that chromatographic purification is also possible

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

• . Its purification was performed by vacuum distillation (18–20 mmHg, 114–116 °C) and stored under argon before subsequent use. The purity (>99.99%) was checked by 1H and 13C NMR spectroscopy. 1H NMR (300 MHz, CDCl3, TMS) δ 5.10 (s, 1H, CH), 4.71 (s, 1H, CH), 4.05 (d, J = 7.3 Hz, 1H, CH), 3.96 (t, J

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• isolated quickly and in good yield, without the need for time-consuming purification steps. At the same time, no cumbersome precautions, such as an inert atmosphere, are necessary. Another fantastic Letter was contributed by Fañanás-Mastral and co-workers, in which a rare copper-catalyzed dimerization

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

• selectivity for the desired product. Despite the advantages of the developed protocol, the homogeneously catalysed procedure negatively impacted the purification and recovery of the products because of the presence of copper salts and complexes. We observed that multiple aqueous washes of the reaction crude

• are required to remove copper salts, and aqueous ammonia has been used to improve the efficacy of liquid–liquid extraction (see Supporting Information File 1 and experimental procedure). This issue made liquid–liquid extraction time-consuming and wasteful, while chromatographic column purification is

• under MW irradiation in less than a third of the time, with the product obtained in pure form without the need for chromatographic purification. A further reduction in reaction time to 1.5 hours was possible at 80 °C, while incomplete conversion was observed after 1 hour (Table 3, entries 17 and 18

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• yield of 50%. In addition, the reaction furnished bis-olefin 5 in 2% isolated yield which is lower than the estimated yield by 1H NMR measurement of the crude mixture (11%). This is due to the partial loss of the product during purification to remove a trace amount of DBC 2, which was generated as a

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

• 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

• subfractions: FB-1 (0.1 g), FB-2 (1.8 g) and FB-3 (0.1 g). Sub fraction FB-2 (1.8 g) was subjected to HPLC purification and eluted with 60% H2O/40% MeOH followed by a linear gradient elution scheme to 100% MeOH for 30 min at a flow rate of 2 mL/min to afford 3 (0.71 mg, tR 20.5 min) and 4 (2.45 mg, tR 28.6 min

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

• reaction time. Even the less reactive aniline gave nearly quantitative isolated yields in less than an hour, while the 1 bar control reaction yielded no detectable products. In addition to the excellent yields, the products were isolated without any purification, using a simple air-drying process to remove

• , salicylic acid, acetic anhydride, acetic acid, hexan-2,5-dione, aniline, hexylamine and 2-phenylethylamine) were purchased from Aldrich and used without any purification. Ethyl acetate, used to dissolve the products for GC–MS analysis (minimum purity of 99.5%) was purchased from ThermoFisher Scientific. The