C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• ·6H2O/meglumine (N-methylglucamine) was found effective. This DES system proved to be a fully water compatible medium for the three-component conversion of glycolaldehyde, allowing the synthesis of a variety of 3-(indol-3-yl)-2,3-dihydrofurans in good yields. Interestingly, the DES (FeCl3·6H2O/meglumine

• than nine steps and gave only 15% yield. No remaining acetal was found in the final product (Scheme 18). The production of lactic acid from dihydroxyacetone or its derivative pyruvaldehyde was investigated on large scale to evaluate the water tolerance of Lewis acid sites of several solid catalysts [86

• co-workers developed an electrocatalytic strategy for the synthesis of HFO from furfural [111]. The very important and key bioactive compound HFO was formed by using water as an oxygen source and chalcogenides such as CuS, ZnS, or PbS as electrocatalysts. CuS nanosheets gave the best performance

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

• -aryl-2-(tert-butylamino)-2-oxoethyl)amino)-4,5-dioxopentanoic acids 5a–l in 50–81% yields (Scheme 2, pathway A; Table 1). The compounds 5a–l were isolated easily by adding water to the reaction mass until it became cloudy, whereupon a precipitate of the product was formed and isolated (all experimental

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• with organic reactions, this chemo-enzymatic strategy has been successfully utilized in the synthesis of complex molecules [22][23]. Enzymatic reactions feature a convenient operation due to their relative insensitivity to water and oxygen, as well as a specificity to certain substrates, resulting in

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

• 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

• isolated and structurally characterised (using, where appropriate, HMBC, COSY and nOe NMR methods; see Figure 3). In general, the yields of these products were rather low, which may stem from poor (co-)substrate solubility in some cases; and/or competitive O–H insertion into adventitious water. On the

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• total charge of 2.2 F/mol was delivered. The reaction mixture was poured into a beaker with 10 mL of distilled water, and a saturated solution of NaHCO3 was added to adjust the pH to ≈7. 10 mL of ethyl acetate were then added, and the two phases were separated. The aqueous phase was then extracted with

• experiments were conducted until a total charge of 4.15 F/mol was delivered. The reaction mixture was then poured into a beaker with distilled water, and a saturated solution of NaHCO3 was added to adjust the pH to ≈7. Ethyl acetate was added, and the two phases were separated. The aqueous phase was then

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• believed to be coordinatively unsaturated zincs at the MOF surfaces, and their lipophilization resulted in a greater than ten-fold increase in the initial rate of the reaction [31]. The promotion of this reaction was attributed to the repulsion of the water by-product by the lipophilic surface, thereby

• catalysis have focused on lipophilization to prevent water-based catalyst decomposition, with only a few investigating how lipophilic pores surfaces can increase catalyst efficiency [32][33], despite enzymes employing such a strategy. The lipophilicity of enzyme active sites tends to improve reaction rates

• by increasing the binding affinity for the lipophilic reactants and by decreasing the energy required to desolvate acid/base amino acid catalysts [34][35]. Lipophilicity has also been found to be beneficial in condensation reactions as the removed water molecules are repelled by the hydrophobic

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

• concentration of the photoswitch in solution: when MeOH or water are present, the lifetimes drop significantly, and particularly at pH 4, as consequence of more favourable intermolecular proton transfer. Calculations show that water molecules bridging between two Z-isomers favour the formation of hydrazone and

• the E-chair isomer [51]. All the compounds show excellent resistance to fatigue. The behaviour of some (hetero)diazocines was also studied in water and solvent mixtures [50][51]. Interestingly, N-acetyl-diazocine possesses overall comparable properties and a longer thermal half-life, and it is also

• soluble in water. For C- and S-diazocine, the absorption band separation of the two isomers is lower in polar solvents, resulting in worse PSS. In particular, for the S-diazocine it was found that the E-chair conformer was bathochromically shifted with increasing polarity of the solvent until completely

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

• ease of modification [42]. Among these, CAs and PAs are representative aromatic macrocycles. They can be made water-soluble and exhibit good biocompatibility through carboxyl or phosphate group modification, showing great potential in biomedical carrier applications. Compared with other artificial

• molecules and high-selectivity binding in drug-controlled release. Many calix/pillar[n]arene hosts are soluble in water, particularly macrocycles that are modified with carboxyl and phosphate groups. Moreover, their amphiphilic modification ability allows easy self-assembly into functional materials like

• solubility, this can be improved through derivatization. Water-soluble calixarene derivatives can be obtained through functional modifications, including the introduction of sulfonic acid, amine, and carboxylic acid groups [57][58][59]. These water soluble macrocycle derivatives can be used to increase the

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

• of EDC permits easy removal of the water-soluble urea-based byproduct with an aqueous wash as opposed to the hydrophobic dicyclohexylurea arising when DCC is utilized, which is more difficult to separate from the hydrophobic malassezione. This route should afford ready access to malassezione for

• 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

• , 0.7mmol, 0.2 equiv) in THF (10 mL) under an argon atmosphere. The reaction mixture was stirred at room temperature for 12 h. After completion of the reaction, the solvent was removed under reduced pressure. The crude reaction mixture was then diluted with EtOAc (100 mL) and washed with water (2 × 40 mL

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• stainless steel demonstrates corrosion resistance in individual exposures to concentrated nitric acid or sulfuric acid due to passivation layer formation. However, during nitration using both acids simultaneously, progressive HNO3 consumption and water generation may reduce acid concentrations below

• temperature, nitrating reagents selection, molar ratio of nitric acid to substrate, molar ratio of nitric acid to sulfuric acid, water content, as systematically discussed in Table 1 (vide infra). The residence time (usually 0–120 s) determines reaction completion, requiring balance between conversion rate

• suppressing byproduct formation from over-sulfonation and minimizing environmental burdens through reduced waste acid discharge. Water content governs the formation equilibrium of nitronium ions (NO2+), the electrophilic nitrating species, thereby dictating the overall reaction rates. In nitration processes

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• a = 16.1017(4) Å, b = 7.7608(2) Å, c = 28.8344(8) Å, and β = 93.3680(10)°. Additionally, the presence of lattice water greatly influenced the molecular packing. The hydrogen bond (H–O–H) lengths in this lattice water ranged from 1.923 to 2.204 Å (Figure 2b). The pyruvylated galactose 6 was utilized

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• the water content in the reaction medium did not exceed 0.7 equiv. In case of LiH2PO2 or NaH2PO2 the model amine formed with similar high yields of the target product (65–70%) (Table 1, lines 2 and 3) both in the presence and in the absence of H3PO2. On the contrary, Rb, K and Cs in the absence of

• the further study. Using the optimal K2CO3/H3PO2 ratio 0.125/0.5, it was found that 78% yield of the model amine could be reached at lower temperature (110 °C) under prolonged reaction time (Scheme 2). The water content in the system had a crucial influence on the reaction outcome: an excess of the

• water led to the drop of the yield while comparably low amounts (less than 0.7 equiv) were favorable (see Table S2 in Supporting Information File 1). This influence could be explained by hindering of the iminium ion formation in the presence of water. Thus, the optimization of the reaction conditions

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

• generated nitrile oxide seems to be less significant. It was found that the low solubility of products containing aromatic substituents in non-polar solvents allows for their isolation by washing the crude reaction mixture with diethyl ether to remove organic impurities and then with water to eliminate

• cases, after the reaction time had expired, the solvent was removed in vacuo. The residue was washed with 2–3 small portions (0.5–1 mL) of Et2O and water giving a solid precipitate of the product (compounds 5a–d, 5f–h and 5k–l). Compounds 5i and 5j were isolated from the reaction mixtures by column

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

• pharmaceutical ingredients (APIs) [8][9][10][11] and pesticides [12], or metabolic labeling molecules in plant science [13], to name a few important applications. The CuAAC reactions can be easily carried out under mild reaction conditions and exhibit excellent functional group tolerance [7]. While water has

• been characterized as an ideal solvent for click reactions, the limited solubility of most organic substrates could limit its application. Thus, the transformations of either water-insoluble or solid compounds require a solvent to establish high reaction performance, i.e. homogeneous solutions with low

• obtained for Cu sources in different solvent systems [40][41]. Although CuAAC reactions can be efficiently performed in water, the moisture content of the organic reaction environment could have a significant effect on the efficiency of a transition-metal-catalyzed reaction. Because CyreneTM is fully

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• the ratio of the total weight of waste to the total weight of the product, is 0.89 for this process. On the other hand, to obtain a ton of CaO from carbide slag, 0.32 tons of water is released. The E-factor for this approach is 0.32, which is approximately 2.8 times less than the approach of obtaining

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

• : To a magnetically stirred solution of the thioketone 7c (833.0 mg, 4 mmol) in 5 mL pentane, placed in a water/ice bath, dry solution of diazomethane in pentane was added dropwise until the red color of starting 7c vanished. The colorless solution was cooled down in a dry ice container, and after few

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• -water ratios to establish initial conditions (Supporting Information File 1, 2.1 Solvent screening). Diphenyliodonium triflate (1a) and 1-isocyano-4-methylbenzene were used as model substrates. Taking into account the possibility of iodonium salt decomposition under irradiation we carried out an initial

• DIPEA as an organic base but the yield of 2aa was very low and we observed a range of byproducts, mainly amine addition instead of water (see Supporting Information File 1, 2.2 Preliminary and Additional Experiments, Figures S5 and S6). Afterwards, we evaluated the other crucial parameters for

• that bulky isonitriles effectively shield the radical or cationic centers in intermediates X1 or X2, thereby preventing multiple additions of isonitrile to give the highest yields for benzamides 2be and 2ge among the scope of isonitriles. In the final step of the reaction, the addition of a water

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

• , and the organic phase was extracted with 3.5 M aqueous ammonia solution (1 × 10 mL) and distilled water (2 × 10 mL). The organic phase was washed with brine, dried over sodium sulphate, and filtered. The solvent was removed under reduced pressure to obtain a pure product. Where required, the residue

• h, and the catalyst was then removed by filtration and recovered where required. The solvent was evaporated under reduced pressure. The resulting residue was dissolved in 10 mL of CHCl3, and the organic phase was extracted with distilled water (2 × 10 mL). The organic phase was washed with brine

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

• addition of water to acetonitrile (Figure 3) lead to increase of the content of the keto tautomers, but the enol form is still present. As suggested by the theoretically predicted chemical shifts of the tautomeric proton (Table 1), the use of NMR could shed more light on the tautomeric composition in

• solution during 20 min. The resulting red-orange mixture was stirred at 0 °C for 2 h, and at rt for 15 h. The mixture was neutralized with 1 N aqueous sodium hydroxide, filtered, washed with cold water (5 mL) and dried under vacuum. The dark orange crude material was purified by flash column chromatography

• , 3.5 mmol) and 1 N aqueous HCl solution (12.0 mL) and methanol (7.0 mL). The mixture was stirred at rt for 2 h, then cooled in an ice bath to 0 °C, and treated slowly with a cold solution of sodium nitrite (0.38 g, 5.5 mmol) in distilled water (3.0 mL). The mixture was left stirring at 0 °C for 2 h. In

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

• dried under reduced pressure, to yield 7.5 g of crude extract. Fractionation and isolation of compounds 1–4 The crude extract (7.5 g) was subjected to fractionation by Kupchan partitioning [33]. The extract was dissolved in water (300 mL) and dichloromethane (300 mL × 3) and placed in a separating

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

• generation. Using water as pressure transmitting fluid, the reaction vessel is immersed in water minimizing fire hazard during the reactions. Finally, most procedures can be carried out at ambient temperature, improving safety and energy efficiency. Energy efficiency is also supported by the nature of the

• instrument is depicted in Figure 1. The core of the instrument is the intensifier which generates the required pressure by amplifying the relatively low pressure (about 140 psi) supplied by an air compressor. The intensifier pressurizes the water in the pressure chamber where the sealed samples are placed

• . Water is used as a pressure transmitting medium that has relatively low compressibility, readily available, and non-toxic. Results and Discussion HHP-assisted synthesis of 1,3-dihydrobenzimidazoles Heterocycles are extremely versatile compounds and are used as building blocks for fine chemicals and

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

• -on of emission upon induced aggregation in alcohol–water mixtures [1]. This chromophore class has been extensively developed in recent years, even to aggregation-induced emissive (AIE) multichromophores [2] and even bichromophoric fluorimetric sensors [3][4]. The retrosynthesis of the title compounds

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