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

• intermediate 7, the carbonyl oxygen interacts with AlCl₃, enhancing the electrophilicity and promoting the rearrangement to form stable oxonium ions. The removal of water from 7 is facilitated by protonation, producing reactive carbocations which undergo dehydrative aromatization to produce products 8

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

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

• accumulation in soil and water [17]. The shortage of natural resources in tandem with the increasing market demand for gold are driving the need to obtain this commodity from low grade ores, typically containing less than 1 wt % in gold, materials of difficult extraction, such as the gold-bearing silicates and

• -former, that is, a substance that causes the precipitation of the product as a solid. In this context, the addition of anti-solvents to aqueous solutions is a common strategy in precipitate formation. In 2023, the same research group showed that various solvents, some miscible with water and others not

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

• amount of water was added to activate the boronic species and to dissolve the inorganic base under otherwise inert conditions. The reaction mixture was then stirred at room temperature overnight. Under these conditions, a variety of boronic acids with different steric and electronic properties was

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

• , dried over sodium sulfate, and freshly distilled prior to use. All solid aldehydes were used after recrystallization from petroleum ether (PE, 60–90 °C fraction) or a mixture of ethanol and water. All dialkyl 3-aryl-1-sulfonylaziridine-2,2-dicarboxylates 1 were synthesized by previously reported

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

• 2.1.1 Stoichiometric reagents: Anhydride formation is one reliable method to activate the carboxylic group of cinnamic acid. For instance, in 2020, Longobardo and DellaGreca utilized isobutyl chloroformate in water to construct an O-protected amide derivative 2 of hydroxycinnamic acid 1 with an

• excellent yield (Scheme 2) [32]. The formed anhydride 3 was smoothly converted to the amide at room temperature. This method provides a green approach by allowing cinnamic acid derivatization in water as a benign solvent. Similarly, Rajendran and Rajan (2023) reported a one-pot transamidation of cinnamamide

• -branched (L/B) selectivity of >20:1. The reaction involves the formation of palladium hydride (Pd–H) 270 as the key species followed by alkyne and CO insertion reactions via 271 and 272 (Scheme 68A) [116]. On the one hand, Jia and co-workers (2021) utilized environmentally benign water as the hydrogen

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• carbon nanomaterials category in view of their stability, water affinity/dispersibility, and low toxicity [1][2][3][4]. Such nanomaterials significantly absorb in the 280–350 nm region due to a wide range of π–π* (C=C) and n–π* (C=O) transitions in both the core and on the surface of the particles. CDs

• dissolved or suspended in water, and the resulting mixture transferred to an autoclave and treated at a temperature ranging 140–200 °C; the treatment yields CDs with an amorphous structure. The synthetic procedure, as well as the structural and morphological characteristics of these materials, have been

• types of CDs and aims to promote the use of these sustainable materials, it opens the way for further exploitation of such compounds in visible-light-catalyzed reactions. UV–vis spectra of the CDs. All the measurements have been performed in water, except for CD-a-GLU, where a H2O/acetonitrile 1:1

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• , tetrabutylammonium iodide (TBAI), and water significantly accelerated aryne generation, thereby increasing its local concentration. This favored aryne coordination to the palladium center, followed by CO insertion and reductive elimination to furnish phenanthridinones. In contrast, when dppm was introduced

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• that a tripodal hexaurea receptor L (Figure 1b) could selectively and reversibly extract sulfate and phosphate anions from water into organic phase (under pH control) [30][31][32][33]. Single crystal structures of the receptor–K2SO4 complex in the presence of 18-crown-6 clearly displayed ion-dipole

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• ). Notably, the reaction was also successful in water, affording the target product in moderate yield (Table 1, entry 5, 51% yield). Next, to further improve the yield, a mixed solvent of iPrOH and H2O was examined. The reaction conducted with a solvent ratio of iPrOH/H2O = 4:1 gave an 83% yield (Table 1

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• classical azobenzenes. Heterocyclic rings offer, for example, enhanced polarity, electron pairs for metal coordination [27], better water-solubility, and variable pKa [28][29]. Special attention has been given to 5-membered N-heterocyclic azobenzenes, which not only maintain the azobenzenes properties but

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

• pyrrolidine-2,3-diones 3b–e are not expected to affect the scope of the reaction (Scheme 2, Table 1). When the reaction between 3a (1 equiv) and methylamine (4) (4 equiv, 40% in water) was carried out in absolute ethanol (0.3 mL) at reflux, 4-(1-methylamino)ethylidene-1,5-diphenylpyrrolidine-2,3-dione (5a

• ) was obtained in 80.8% yield. Gratifyingly, substrate 3a is well soluble in methylamine solution (40% in water) and conducting the reaction between 3a (1 equiv) and methylamine (4) (40% in water, 0.3 mL, 47 equiv), without any other solvent added, the yield of product 5a increased to 92.2% (Table 1

• ). Therefore, excess methylamine (40% in water, 47 equiv), served as both the solvent and nucleophilic reactant in the above reaction. In the 1H NMR spectrum of 3a, there are two doublets of doublets at 4.40 ppm and 4.49 ppm corresponding to two methylene protons (CH2) which are diastereotopic and therefore

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• and nickel were used as the cathode and graphite as the anode, the efficiencies of the processes were very close to each other. The use of dry acetonitrile as the reaction medium significantly reduced the yield. These results indicate that water plays a crucial role in this reaction, as its

• optimization of the reaction, an HTe−Chem reactor was used in the presence of Me₄NOAc as the electrolyte. The use of NMP and Me₄NOAc was beneficial, as in many cases, adding water led to the precipitation of the desired product from the reaction mixture. A wide range of iminophosphoranes were synthesized

• according to the following mechanism via an anodic trimethylsilyl cyanide radical formation (Scheme 24). The formation of the Ph₃P=O as the side product was assumed to be due to the presence of water or oxygen in the reaction mixture, which competes with the aminating reagent. Electrochemical O–P bond

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

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• α-ᴅ-mannoside (MeMan) measured on the same plate as reference. This leads to relative inhibitory potencies, so-called RIP values. Because of limited water solubility, the samples had to be dissolved in DMSO and therefore, the effect of pure DMSO was also tested in every individual assay (cf

• , Figures S13–S16), the analysis of the testing results shows that determination of the inhibitory potencies of the various isomers is indeed valid in spite of the limited water solubility of the samples. Looking over the measured inhibitory potentials, it can be concluded that (i) the isomeric state of the

• like glycoclusters 1 and 2 are capable of many conformational alternatives and therefore, the control of molecular shape by photoisomerization of azobenzene linkers has its limitations. In addition, water solubility requires improvement. Furthermore, our study, combining synthesis, analysis of

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

• in 40 µL of water, followed by the addition of 12 µL of buffer (250 mM HEPES, 500 mM KCl, pH 7.0) and 6.0 µL of MgCl2 solution (20 mM). The aptamer was annealed by heat shock at 90 °C for 2 minutes and cooled on ice. Then, 2.0 µL of a ligand stock solution (3.0 mM, in DMSO) was added. The final

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• alkyl sulfate ionic groups. The X-ray crystal structure of the C1·Me6CHDA complex is reported. Host C1 is significantly less soluble in water (4 mM) compared to the analogous acyclic CB[n] host M1 which features sulfonate ionic groups (346 mM). Host C1 does not undergo significant self-association

• and water [1][2][3][4]. Building on this fundamental knowledge, supramolecular chemists created a variety of functional systems including supramolecular polymers, sensing ensembles, molecular machines, supramolecular separation phases, and drug delivery systems [5][6][7][8][9]. A primary subfield of

• important role driving the inclusion of Me6CHDA inside of C1 to form the C1·Me6CHDA complex. Of course, the inclusion of the hydrophobic cyclohexyl moiety inside the cavity of C1 provides a hydrophobic driving force for complexation in water. Given that C1 is a tetraanion and that Me6CHDA is a dication, an

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• , conformations in which the two C–F bonds are aligned gauche will be favoured in water due to their high molecular dipole moment. A final layer of complexity is afforded by the stereochemistry of the 1,2-difluoroalkane motif: the various conformational factors described above will aggregate differently depending

• upon whether the 1,2-difluoro stereochemistry is threo or erythro. For example, the diastereoisomeric difluorinated stearic acids 14 and 15 (Figure 3) are found to have very different physical properties [28]. When deposited into a monolayer above a water phase, the threo-isomer 14 occupies a small

• be altered, too [44]. For example, consider compounds 26 and 27 (Figure 4), which are fluorinated analogues of the multiple sclerosis drug gilenya (25) [45]. The syn,anti-fluorinated stereoisomer 26 has a much higher water solubility than gilenya (25), attributable to the presence of new polar bonds

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

• fluorinated amino acids that can be synthesized from a single starting material is a unique feature of this method, making it an important cornerstone of fluoropeptide chemistry. Experimental General information Air- and hydrolysis-sensitive reactions were carried out under exclusion of air and water in

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

• ]. Accordingly, the electrolysis of monoester 9a in a 2:1 MeCN/H2O mixture in the presence of 0.025 M LiClO4 solution under constant current conditions (j = 12 mA/cm2) with graphite both as an anode and a cathode material afforded the desired N-tosylpyrrolidine 6a in 67% yield (Table 1, entry 1). The water

• amount of water was reduced from 33% to 17% (Table 1, entry 8 vs entry 7), an observation that might be useful for substrates of low aqueous solubility. However, further reduction of water amount to 5 equivalents completely inhibited the anodic oxidation of 9a, and only traces of the desired 6a were

• (entry 10, Table 1) in deuterated solvents (Scheme 2; for details, see Supporting Information File 1, page S40). Surprisingly, the electrolysis in a 5:1 mixture of MeCN-d3 and water delivered 11d without deuterium incorporation (Scheme 2, reaction 1). In contrast, the formation of deuterated 11d-D was

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• available and inexpensive Ru(bpy)3, along with a water-soluble, air- and moisture-stable Ni(dabpy)Br2 catalyst. Moreover, they demonstrated that this system works efficiently in aqueous conditions, making it highly suitable for applications involving antibodies. These characteristics make the method highly

• facilitated a site-specific covalent linkage to the antibody, resulting in the formation of a DAR 2 ADC precursor. For their ADC design strategy, the group selected a polyethylene glycol (PEG) linker, as it enhances the water solubility of the ADC, while the payload consists of the cytotoxic agent DM1, which

• aqueous media is essential for the modification of antibodies, as these biomolecules are typically dissolved in water or aqueous buffers to maintain their stability and activity. Antibodies are sensitive to their environment, and using a non-negligible amount of organic solvents or harsh chemical

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

• Agilent 1100 series preparative HPLC system [ChemStation software (Rev. B.04.03 SP1); binary pump system; column: Kinetex 5u RP C18, dimensions 250 × 21.20 mm; mobile phase: ACN + 0.05% trifluoroacetic acid (TFA) and water + 0.05% TFA; flow rate: 20 mL/min; diode array UV detector; 226 fraction collector

• mixture was stirred at room temperature overnight. The reaction mixture was suspended in water (25 mL) and extracted with CH2Cl2 (2 × 25 mL). The combined organic layer was evaporated to dryness to give a residue, which was dissolved in methanol (300 μL) and purified by preparative HPLC [ChemStation

• software (Rev. B.04.03 SP1); binary pump system; column: Kinetex 5u RP C18, dimensions 250 × 21.20 mm; mobile phase: ACN + 0.05% trifluoroacetic acid (TFA) and water + 0.05% TFA; flow rate 20 mL/min; diode array UV detector; 226 fraction collector. A gradient from 47 to 72% solvent B in 50 min was used

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• hydantoins [19][20], we aim towards creating a more efficient procedure to access hydantoins. We are interested in the synthesis of hydantoins from amino acids and potassium cyanate in water due to its simplicity and environmental friendliness, which also precludes the use of water-sensitive and highly toxic

• Discussion As the first step of Urech hydantoin synthesis involved the N-carbamylation of amino acids, we carried out the microwave-assisted synthesis of urea derivatives in water, utilizing ʟ-phenylaniline as the representative amino acid. The optimal conditions for the N-carbamylation of ʟ-phenylaniline

• were first verified using different equivalents of KOCN at different temperatures in water under microwave heating conditions (Scheme 1, Table 1), and 5.0 equiv of KOCN and microwave irradiation at 80 °C produced the best yield for H1a (Table 1, entry 2). Inspired by the simplicity of the procedure, a

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

• carbon atom, due to the readiness for losing a water molecule. Formaldehyde is commonly used in its polymeric form (paraformaldehyde) or in a 37% aqueous solution (formalin). The exceptional solubility of formaldehyde in water or biobased solvents, such as ethanol and glycerol, enhances the feasibility

• [17][18]. An important drawback of this solvent is the difficulty of its removal from the reaction crude, and extractions with water are commonly employed before purification. Depending on the reaction conditions, DMSO can be transformed into different products, e.g., under redox conditions, DMSO can

• ], DMSO [64], water, and even neat conditions [62]. In some cases, the same dihalomethane can be used as both the reactant and solvent. For example, Aguilar et al., proved that when using CH2Cl2 as both a solvent and a C1 source, they could obtain propargylamines 29 with good yields from secondary amines