Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• -linking of polymers (such as PLGA and PEG), inorganic materials (such as gold and silica), or biomolecules (lipids and proteins), enabling efficient drug loading and controlled release [66][67][68]. Among them, amphiphilic CAs that incorporate both hydrophilic groups and hydrophobic alkyl chains through

• hybridized with various inorganic materials, such as metal-organic frameworks (MOFs), mesoporous silica nanoparticles (MSNs), metal nanoparticles, and carbon materials [87]. By designing through electrostatic and non-covalent interactions, PAs can be used as "molecular switches" to construct mechanized MOFs

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

• , ON, Canada). Reactions were monitored using thin-layer chromatography on aluminium-backed silica plates (Sigma-Aldrich) using either UV-light (254 nm), iodine, KMnO4, phosphomolybdic acid, or p-anisaldehyde for visualization. Tetrahydrofuran (THF) was dried and distilled over sodium/benzophenone

• ), and brine (100 mL). After drying over anhydrous MgSO4, the solvent was removed in vacuo and the crude product was purified by flash chromatography on silica gel (EtOAc/hexane; gradient 1:10 → 1:2) to give 21 as a colorless solid (6.7 g, 80%, 2 steps); Rf = 0.5 (EtOAc/hexane 1:2); mp 50–52 °C (lit. mp

• with EtOAc (3 × 50 mL) and the combined organic layers were washed with water (100 mL) and brine (100 mL), and then dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel (EtOAc/hexane gradient 1:10 → 1:1, 1% AcOH

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• . tuberculosis [121]. The TMS-glycosides were prepared from the corresponding hemiacetals by acid-catalyzed silylation, involving a silica gel-promoted in situ anomerization of the O-TMS-β-glycoside to its more thermodynamically stable α-counterpart [121]. This protocol enabled the efficient synthesis of TMS

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

• standard. Analytical thin-layer chromatography (TLC) was performed with silica gel 60 Merck F254 plates. Column chromatography was performed with silica gel 60N (spherical neutral). Recyclable preparative high-performance liquid chromatography (HPLC) was carried out on a Japan Analytical Industry Model

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• hybrid decamer 3 in a previous report [26], via a Suzuki–Miyaura cross-coupling reaction between dibromo precursor 1 and borylated precursor 2 (Scheme 1). The resulting mixture was successfully separated by column chromatography on silica using CH2Cl2/n-hexane as an eluent to give icosamer 4 in 6% yield

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

• chromatography on silica gel using DCM as eluent. Design and synthetic strategies for the target hydantoin/1,2,4-oxadiazoline spiro-compounds. Atropoisomerism of ortho-substituted spiro-compounds 5b and 5d. Cytotoxicity investigation of hydantoin/1,2,4-oxadiazolines 5 (MTT test, HCT116 cell line) and selected

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

• Commercial chemicals and solvents were used as received. If not stated otherwise, products were purified by filtration through short silica gel plugs (200–400 mesh) by using freshly distilled solvents as eluents or by recrystallization. Melting points were determined in capillaries with an Aldrich Melt-Temp

• evaporated, and the residue was analyzed by 1H NMR. Depending on the composition of the crude product, this material was either separated by preparative layer chromatography on the plates coated with silica gel (CH2Cl2 as the mobile phase) (separation of 9h and 10h) or crystallized from hexane/CH2Cl2 mixture

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

• harness their Lewis-acidic and weakly oxidizing properties, respectively. In addition, microwave irradiation increases the reaction rate considerably. Furthermore, the use of a solid Cu(I) catalyst immobilized on an aminated silica support allows for a heterogeneous and cost-effective process, featuring

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

• completed in 1.5–2 h. A solid Cu(I) catalyst supported on aminated silica made the process cost-effective and heterogeneous, thus simplifying work-up and minimising free copper in solution. The catalyst was found to be regeneratable and reusable for up to eight cycles. The optimised method facilitated the

• synthesis of various benzoxazole derivatives, demonstrating its versatility and practical applicability. Keywords: aerobic oxidation; copper; grafted silica; heterogeneous catalysis; microwave; Introduction 2-Aminoazoles are nitrogenous heterocyclic compounds of high relevance due to their biological and

• supported copper(II) catalysts on covalently modified silica [51][52], we have set out to develop a new heterogeneous catalyst with atomically distributed active sites for the mild and efficient C–H amination of benzoxazole. This approach was chosen because the silica derivatisation and copper deposition

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• foundation, the same group in 2024 developed a series of structurally refined aza[7]helicenes (compounds 12a and 12b) under modified Scholl reaction conditions [25]. These products were obtained as optically active diastereomers, which were successfully separated using silica gel chromatography. Additionally

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

• Fluorochem and used as received. The solvents used for the experimental synthesis (HPLC grade) were purchased from Sigma-Aldrich. All other materials were commercial products of analytical grade and used as supplied. Analytical TLC (thin-layer chromatography) was performed on Merck silica gel 60 F254

• on silica gel, using dichloromethane/ethyl acetate 6:1 as eluent to obtain the pure product as bright orange solid (0.31 g, 62% yield). 1H NMR (500 MHz, CDCl3) δ 8.93 (dd, J = 1.2 Hz, 4.6 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 9.5 Hz, 1H), 7.49 (t, J = 8.0 Hz, 2H

• formed, was washed with water several times and dried. The crude material was purified by column chromatography on silica gel, eluting with dichloromethane. Evaporation of the solvent afforded the pure target compound as orange solid (0.26 g, 38% yield). 1H NMR (500 MHz, DMSO-d6) δ 14.7 (br s, 1H), 8.90

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

• solution was stirred for 10 min in an ice bath, then iodonium salt 2a or 2f (1.5–2.0 equiv) was added in one portion. The reaction vessel was removed from the ice bath and the reaction mass was stirred for 6–60 min, then transferred to a silica gel column and the corresponding 2-sulfonyl-2,3-dihydro-1,2

• (1.5 mL) was added dropwise. The reaction vessel was removed from the ice bath and the reaction mass was stirred for 10–30 min, then transferred to a silica gel column and the corresponding 2-sulfonyl-1,3-thiazole 3 was isolated. X-ray structure determination of 3aa. Crystal data for C21H21N3O3S2 (M

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• in Table 1. The yield of compounds 1 after flash chromatography on silica gel under modified conditions (B) are significantly higher than under standard conditions (A). The results demonstrate the broad applicability of the optimized reaction conditions. Acid chlorides with electron-withdrawing (-CN

• ® and purified by flash chromatography on silica gel (n-hexane/acetone 3:1). Then, the crude product was suspended in n-hexane, the supernatant separated by filtration and the precipitate was dried under vacuum to afford aroyl-S,N-ketene acetal 1i (1.78 g, 4.93 mmol, 99%) as a yellow solid. Mp 159 °C

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

• chromatography on silica gel. Recent approaches for the synthesis of β-ketophosphonates by the oxyphosphorylation of unsaturated compounds. The scope of the discovered copper(II)-mediated phosphorylation of enol acetates. Gram-scale synthesis of 3a. Control experiments. Proposed mechanism for copper(II) mediated

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• chromatography on silica gel because of their low polarity and poor solubility in n-hexane. On the other hand, nitration of [3.3.3] gave solely the six-fold nitrated product due to low solubility of the starting material [46]. The current reaction is the first practical method for the selective

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

• column chromatography (and additionally by HPLC for the toluene reaction), the reactions also gave comparable yields of compound 2 (70% for toluene/silica and 82% for only phenethylamine at room temperature). Only the tele-substituted product was observed in either reaction mixture, consistent with

• mixtures were separated by silica flash column chromatography, and in some cases, were subsequently separated by HPLC where required. All reactions gave easily isolated product in high purity (≥95%), with yields ranging from 18% to 87%. No ipso-substituted products, and no triazole–imidazole rearrangement

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• was refluxed over sodium with benzophenone as an indicator and freshly distilled prior to use. Column chromatography was performed on silica gel (normal phase, 200–300 mesh) from Anhui Liangchen Silicon Material Co., Ltd. or basic aluminum oxide (pH 9–10) from Shanghai Titan Technology Co., Ltd

• . Petroleum ether (PE, 60–90 °C fraction) and ethyl acetate (EA) were used as eluent. Reactions were monitored by thin-layer chromatography (TLC) on GF254 silica gel plates (0.2 mm) from Anhui Liangchen Silicon Material Co., Ltd. The plates were visualized by UV light. 1H NMR (400 MHz) and 13C NMR (101 MHz

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• further purification. For column chromatography, 70–230 mesh silica 60 (E. M. Merck) was used as the stationary phase. Electrospray ionization–high-resolution mass spectra (ESI–HRMS) were acquired on a SCIEX X500 QTOF instrument in the positive ion mode. A Büchi melting point B-545 apparatus was used to

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• . Chemical reagents and solvents were purchased in the highest available quality from commercial suppliers (Merck/Sigma-Aldrich, ABCR) and used without further purification. Analytical thin-layer chromatography (TLC) was performed on Macherey-Nagel Polygram® SIL G/UV254 plates. 0.2 mm silica gel 60 for

• Na2SO4 and concentrated to dryness. Finally, the crude compound was purified via silica gel chromatography using 50–70% ethyl acetate in cyclohexane as gradient. General procedure B. The product obtained in general procedure A was dissolved in ethanol mixed with 4-cyanophenylacetonitrile and 8 drops of

• obtained in general procedure B was dissolved in dichloromethane and cooled to 0 °C under argon atmosphere. Then, triphenylphosphine and carbon tetrabromide were added and stirred at room temperature for two hours. Afterwards, the entire mixture was loaded on a silica gel column and eluted with 100

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

• ) was carried out on aluminum plates coated with silica gel 60 F254 (Merck, Darmstadt, Germany). The TLC plates were analyzed using UV light at 254 nm. Flash chromatography was performed on silica gel 60 M from Macherey-Nagel (grain size of 40−63 μm). The conditions are given in the form “(A/B = a:b

• , Torrance, CA, USA) was used. H2O and MeCN, both containing 0.1% (v/v) TFA, served as eluents. Fmoc-protected amino acids were detected at 220 nm. For a chiral analysis, a CHIRALPAK ZWIX(−) column ((R,R)-ACHSA immobilized on 3 μm silica gel, 250 × 4 mm, Chiral Technologies Europe, Illkirch Cedex, France

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• quench of a transient N-acyliminium species was found to be a major side-reaction as evidenced by the formation of an open-chain hemiaminal 10a (the hemiaminal could not be isolated due to the instability on silica gel). Screening of other supporting electrolytes revealed that basic salts (K2CO3, Na2CO3

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

• notably. Later, the same group developed an alternative method by using glyoxylic acid immobilized on silica, and the reaction conditions were optimized using microwave irradiation and avoiding the use of solvent or additional catalysts [93]. In this way, derivatives of 42a were obtained in good yields

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

• Barnstead NANOpure Ultrapure Water system, producing water with a final resistance of at least 18 MΩ); and silica gel (Sigma-Aldrich, 70–230 mesh, 60 Å). For HPLC separations: acetonitrile (Fisher Scientific ACS grade); toluene (Fisher Scientific, ACS grade); and heptane (Mallinckrodt Chemicals, ACS grade

• were extracted with Et2O and washed four to six times with doubly distilled water removing the aqueous layer each time. Anhydrous MgSO4 was added to the organic layer and passed through silica gel with DCM as the eluent. The organic layer was then concentrated to dryness. Yield (isolated): 9-H-10-BnF

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