Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• chromatography. Diastereoisomeric ratio (dr) determined by 1H NMR of the crude reaction mixture. Plausible mechanism and X-ray structure of compound 5aca. Optimization of the reaction conditions.a Supporting Information Supporting Information File 14: Detailed experimental procedures, characterization data, and

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• chlorine gas, with the reaction conducted by stirring the pyrazolinone with TCICA in DCM for 18 hours. Bimanes can be purified easily using column chromatography with silica gel as the stationary phase, with the compounds Cl2B, Me2B, and Me4B only requiring neat DCM as the eluent. After chromatographic

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• novel 2,6-diamino preQ1 analog 2 (DPQ1) by hydrogenation of 8 (DPQ0 [32]) (Scheme 2). In this case, however, a final purification step (by reversed-phase chromatography) was required. Notably, using the hydrogenation conditions described here, we were also able to streamline our previously reported 7

• mild reduction with methanolic sodium borohydride. Upon purification by reversed-phase chromatography using aqueous hydrobromic acid as eluent (0.5% in H2O), a considerable fraction of the alcohols was already converted to the desired bromides 4c,d. Only in the case of 4b, no deoxygenative bromination

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• chromatography [1]. Sometime later, kinetic resolution (KR) emerged. This method is based on the different reaction rates of each enantiomer in a racemic mixture when they are reacted with a reagent, a chiral catalyst, or an enzyme. This process results in obtaining the less reactive enantioenriched enantiomer

• ] using 20 mol % of catalyst A and 20 mol % of p-nitrobenzoic acid (PNBA) as co-catalyst in different solvents at room temperature. The results obtained are summarized in Scheme 3 and Table 1. The progress of the reaction was monitored using thin-layer chromatography (TLC) and 1H NMR analysis of the

• a one dm path length, and concentration was given in grams per 100 mL. TLC analysis was performed on glass-backed plates coated with silica gel 60 and an F254 indicator and visualized by either UV irradiation or staining with phosphomolybdic acid solution. Flash chromatography uses silica gel (230

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• extractive workup followed by reversed-phase chromatography and its structure was unambiguously confirmed by X-ray crystallography (Table 1, graphic). Gratifyingly, a two-fold increase in the yield was achieved by a slight reduction of the current density to j = 8 mA·cm−2 (entry 2 vs entry 1 in Table 1). A

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• able to adapt this chemistry to work in situ, allowing soluble metastable imine frameworks to be trapped as amides [38]. The adapted cages were soluble, and were now stable enough to be purified by gel-permeation (size-exclusion) chromatography (useful when precipitation is not possible), which is

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• to generate an inseparable byproduct. By contrast, the byproduct derived from Boc-protected amines has a significantly different retention time on HPLC and could be removed by regular silica gel chromatography. Because the formation of 5‒7 posts a significant purification challenge, we sought to

• silica gel column chromatography. The LUMO and electrostatic charges of thalidomide and its derivatives by DFT calculation at the ωB97X-D/6-311+G** level. The synthetic route for iVeliparib-AP6. The conversion of byproduct 6 to 10 to facilitate its removal. Effects of the length and functionalization of

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• temperature (23 °C). Chromatography was carried out on columns filled with Al2O3 of II–III degree of activity according to Brockmann. Melting points were determined on a Fisher-Johns melting point apparatus. 1,1,2-Trimethyl-1H-benzo[e]indolenine (2a, 98%, Alfa Aesar), 2,3,3-trimethyl-3H-benzo[g]indolenine (2b

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• -dihydronaphtho[1,2-b]furan-3-carboxylate 4a,b with a total yield of up to 73% (ratio 3a/4a = 2:1; 3b/4b = 2:1, according to 1H NMR spectroscopy) (Scheme 4). Using preparative chromatography, the mixture was separated into individual substances. In turn, alkyl 7,7-dimethyl-4,9-dioxo-6,7,8,9-tetrahydro-4H-furo[3,2

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• (15 g) was analyzed by LC–MS. Thereafter, it was fractionated by vacuum liquid chromatography (VLC) using silica gel as a stationary phase. The elution procedure was performed using a chromatographic scheme of two different gradients as follows: 1) n-heptane/EtOAc (1:0, 7:3, 3:7, 0:1) followed by

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• days (TLC or NMR control). After completion of the reaction, the solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel using chloroform as eluent. ((1S,4S)-Bicyclo[2.2.1]hept-5-ene-2,2-diyl)bis(phenylmethanone) (8) and phenyl((4aR,7aS)-2-phenyl

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• solution, extracted with ether, washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using n-hexane and ethyl acetate 95:5 to give 1.4 g of I2(a) in 50% yield. 1H NMR (300 MHz, CDCl3, TMS) δ = 2.55 (d, JHF = 3.2 Hz

• brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using n-hexane to give 2.8 g of I4(a) in 56% yield. 1H NMR (300 MHz, CDCl3, TMS) δ = 2.42 (s, 3H, CH3), 7.29–7.34 (m, 1H, aromatic H), 7.40–7.46 (m, 1H, aromatic H), 7.49

• reaction mixture was neutralized by HCl aqueous solution, extracted with ether, washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using n-hexane and ethyl acetate 8:2 and recycling HPLC using chloroform as the

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• specific MCR-based scaffolds as precursors and employing the abundant and inexpensive formamide as a C1 feedstock under neat conditions, we were able to efficiently access substituted thieno-, quinolino- and indolopyrimidones without the need of column chromatography. Further, a single-crystal X-ray

• obtained 15 diversely substituted heteroannulated pyrimidones, employing privileged thiophene, quinoline and indole scaffolds in a rapid fashion, without the need of column chromatography, in a parallel setup. Heteroannulated pyrimidones in drug discovery: blockbuster drugs that are based on the privileged

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• JMS-T100GCV or a JEOL JMS-T200GC spectrometer. All the reactions were conducted under argon or nitrogen. Materials: Column chromatography was conducted on silica gel (Silica Gel 60 N, Kanto Chemical Co., Inc.). Toluene and N,N-dimethylformamide (DMF) were purified by a solvent-purification system

• . After removal of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (hexane/EtOAc = 10:1) to give 3bb (76 mg, 98%) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.15 (d, J = 8.2 Hz, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.75–7.67 (m, 4H), 7.58 (ddd, J = 8.2, 6.9, 1.2

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• atmosphere, special precautions, and with isolated yields up to 60% [14][15]. Due to the formation of side products, final purification of the amino derivatives requires the use of either multiple separation techniques, chromatography, or distillation [15][16][17][18] (Scheme 1). Differently from lithium

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• consists of a fluid delivery system, mixing tools, reactors, quenching units, pressure regulation units, and collection vessels. The fluid delivery is normally executed using either high-pressure liquid chromatography (HPLC), a syringe, or peristaltic pumps. A passive mixing stage where the reagents are

• products once experiments are performed. Despite this bottleneck, the landscape is evolving, with various practical tools emerging to streamline purification processes. From prepacked silica gel tubes to the precision semipreparative liquid chromatography and the versatile capabilities of various scavenger

• . [70] assembled four complementary PATs, including in-line NMR, UV–vis, IR, and online ultra-high-performance liquid chromatography (UHPLC) to meticulously monitor the intricate three-step linear synthesis of the drug mesalazine (18, Figure 7) with a 1.6 g⋅h−1 throughput. In the first step, the

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• -layer chromatography (TLC). When other typical conditions for Scholl reactions, such as FeCl3 or DDQ/CH3SO3H, were employed to treat compound 10, product 3 was not isolated. Instead, the starting material either remained unreacted or was converted to a complicated mixture of products. It is worth noting

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

• dichloromethane (2 mL) three times. The combined organic extracts were repeatedly washed with water (20 mL) and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude material, which was purified by silica gel column chromatography (hexane

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• , after which the extract was partitioned between EtOAc and H2O. The EtOAc-soluble fraction was subjected to silica gel column chromatography. A detailed analysis of the 1H NMR spectrum of the fraction eluted after the one containing ceratinadins E and F revealed signals corresponding to psammaplysin F (2

• 49.8 ppm were used as internal references. Mass spectra were acquired on a JEOL JMS-T100LP spectrometer. Flash column chromatography was performed using a Biotage Isolera flash purification system. Extraction and isolation The EtOAc-soluble material (2.45 g) of the methanol extract (38.06 g) from the

• sponge Pseudoceratina sp. (order Verongida; family Aplysinellidae), collected in Okinawa, Japan (0.4 kg, wet weight), was obtained following the method described in [8]. In a manner similar to [8], a portion of the EtOAc-soluble material (1.45 g) was fractionated by silica gel column chromatography

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• GeneVac XL4 centrifugal evaporator. All solvents used for chromatography, UV, MS, and [α]D were Honeywell Burdick & Jackson or Lab-Scan HPLC grade. H2O was filtered using a Sartorius Stedium Arium Pro VF ultrapure water system. Reagents used for the total synthesis of Ianthelliformisamine D were purchased

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• that chromatography was not required to isolate the products. At the same time, compound 4i proved to be inactive under the used chlorination conditions, compounds 4g,h underwent partial hydrodebromination in the aryl substituent in the same step, while compound 4j yielded a product with difficult to

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• vial was quickly capped with a Teflon microwave cap. The reaction was heated to 70 ºC for 10 min. The crude mixture was dissolved with DCM (3 mL), the solvent was removed under reduced pressure to furnish a crude product that was purified by flash column chromatography, using silica gel 60 (200–400

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• chromatography. With dipeptides 7e and 7f stereoisomerically pure, we next focused our attention on the preparation of novel peptidic structures to perform some conformational analyses. Starting from the methyl ester 7, each diastereomer was engaged in a classical sequence of saponification in the presence of

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• compounds with high yields (84–92%). The three most promising compounds of the library (13a, 13b, and 13c) were selected for further detailed characterization. In vitro evaluation was performed employing a high-performance liquid chromatography (HPLC)-based methodology, using the fluorogenic histone