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

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

• produced after the first two steps were obtained as single isomers and in moderate yields after a single chromatographic purification, thus making the overall synthetic sequence relatively efficient. Also, thanks to the addition of 1 equivalent of p-xylene, which is claimed to suppress alkene [2 + 2

• oxidation state ruthenium, allowing for a facile purification (simple acidic/basic workup) and is very mild, scalable and high-yielding. However, the yield tends to get rather low (below 25%), if the oxetane bears a heterocycle (e.g., indole or thiophene), most likely due to competing oxidations of the

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• macrolides with hydroxy groups at C20 or C7, identified as borrelidins C–E (Table 1, entries 4, 7, and 8) [19]. Borrelidins CR1 and CR2 (Table 1, entries 5 and 6), amide-containing congeners, were also isolated through bioassay-guided fractionation and purification of marine microorganisms from Costa Rica

• °C and leaving it at the same temperature for an additional 15 minutes, two products, 47a and 47b, were formed. After desulfonylation with sodium amalgam (Na·Hg) in methanol and column chromatographic purification, the anticipated diols 48a and 48b were obtained in 72 and 11% yield, respectively. The

• . Hydroxylation at the (ω-1) position was achieved using the NADH-dependent mutated enzyme variant CYP102A1 3 mDS, a p450 monooxygenase derived from Bacillus megaterium CYP102A1. After chromatographic purification, alcohol 89 was obtained in a 34% yield with a diastereomeric ratio of 82:18. This alcohol was

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

• (Göttingen, Lower Saxony, Germany) Arium™ Pro VF ultrapure water system. Synthetic reagents were purchased from Sigma-Aldrich (St. Louis, MO, USA) and used without further purification. The starting material, 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine (1), was previously synthesised and

• -a]pyrazin-8-amine (2) 5-Chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine (106 mg, 0.4 mmol), was dissolved in phenethylamine (500 µL, 1.6 mmol, 10 equiv) and the reaction mixture stirred at room temperature for 16 h, then pre-adsorbed to silica (≈1 g) overnight. Purification was performed as

• aminated triazolopyrazine library (3–15) 5-Chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine (1, 53 mg, 0.20 mmol) was dissolved in excess liquid amine (500 µL) and the mixture was stirred at room temperature for 16 h. Purification was performed as described in Supporting Information File 1, and

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

• , the process is being applied in Cycladex facilities in Nevada and licensed for use by other companies around the globe [42]. Tests on ores from African mines: In 2020, a variant of the α-CD precipitation method was developed with the aim of acting as a direct purification step for batches of gold ore

• ]. A few years later, the process of gold ore purification was further optimized to achieve yields as high as 98.9%. Using ores from Democratic Republic of Congo (initial sample mass of 400 g, acqua regia dissolution) researchers used a combination of experimental measurements (of yield) and neural

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• after workup. Purifying the bromide 2 via column chromatography was deemed unnecessary after comparing the NMR spectra of the worked-up and the purified product. While the worked-up product 2 exhibited only slight differences in impurities, the yield was significantly reduced due to purification by