The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• (99.999%) was used as carrier gas with a constant flow rate of 1.0 mL min−1. Representative procedure for cycloaddition reactions To a 50 mL single-necked flask, (0.1 g, 0.51 mmol) of C,N-diphenylnitrone, (0.09 g, 0.52 mmol) of N-phenylmaleimide and 1 mL of methyl laurate were added. The flask was

Adaptive experimentation and optimization in organic chemistry

• Artur M. Schweidtmann and
• Philippe Schwaller

Beilstein J. Org. Chem. 2025, 21, 2367–2368, doi:10.3762/bjoc.21.180

• . provide a comprehensive review of machine learning applications in enantioselective organocatalysis, highlighting both achievements and remaining challenges [10]. Guo et al. present an automated flow chemistry system for nitration reactions, combining kinetic modeling with experimental optimization [11

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• under catalytic conditions – may lead to novel strategies for C–H functionalization and fragment coupling, ultimately advancing the field of target-oriented synthesis. Combining Norrish–Yang reaction with flow chemistry technology to realize the continuous operation of the reaction can improve the

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• provides a way to avoid the use of stoichiometric chemical oxidants or reductants and to achieve new transformations that are highly regio- and stereoselective. Though not covered in this perspective, flow chemistry and mechanochemistry are also increasingly popular areas that hold significant potential

• for applications in radical chemistry. Compared with conventional batch synthesis, flow chemistry can improve efficiency and facilitate reaction scale-up [87][88][89][90]. Mechanochemistry allows reactions to be conducted with no solvent or with only a small volume of added liquid, thus providing a

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• configuration). Methods for absolute configuration determination indicated. Extracted LC–MS chromatograms (m/z 304.1) of 4-methoxy-3-methyl-4-oxobutan-2-yl 4-nitrobenzoates. Conditions: CHIRALPAK ID-3 (4.6 × 250 mm, 3 μm) at a flow rate of 0.6 mL/min at 40 °C, with gradient elution from 50% MeOH to 100% MeOH

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• ). Analytical methods. All samples of the kinetic solubility and in vitro permeability assays were analyzed on a Waters Alliance 2695 Separations Module equipped with a 2996 PDA detector, using a Water Xterra RP 18 chromatographic column (100 × 4.6 mm, 3.5 µm) at 45 °C, applying 1.2 mL/min flow rate. For a 7

•  4 was applied at a constant flow rate of 1.0 mL/min. The mass spectrometer operated in sensitivity mode with a capillary voltage of 3.0 kV, source temperature was 100 °C, and desolvation temperature was 350 °C. The cone gas flow was set to 0 L/h and desolvation gas flow to 800 L/h. LockSpray

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

• presence of the photocatalyst provokes an impressive five-fold rise in the conversion rate (3.81 mmol/g) without compromising the high selectivity towards the two trioses (glyceraldehyde, 46.4%, and dihydroxyacetone, 32.9%). Okamoto and co-workers developed a new hydroxyapatite (HAp)-loaded flow system for

• flow reactor. The moderate acidity and the hierarchical tube-type porous nature of SBA-15, as well as the adsorption energy on the surface of 10Cu–5Ni/SBA-15 catalyst, are the key parameters for giving 2-pentanone with high selectivity (78%) (Scheme 52) [180]. Wang developed a new route for the

• trans-4,5-diaminocyclopent-2-enones in hexane/isopropanol solvent mixture under continuous flow conditions (Scheme 56). The scope could be extended to 2-substituted trans-4,5-diaminocyclopent-2-enones by using 3-substituted furfurals [187]. A copper triflate-based analogous strategy was also reported

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

• voltammetric wave, the aqueous solution was actively stirred with a magnetic stirrer in an atmosphere of constant inert gas flow. Starting materials. Methylphosphonic dichloride MeP(O)Cl2 and methyl dichlorophosphate (MeO)P(O)Cl2) [30] were prepared according to literature procedures. Phosphorus oxychloride P

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

• diimines of aromatic aldehydes with trans-1,2-diaminocyclohexane for the synthesis of enantiopure tetrasubstituted piperazines has been investigated by an electrochemical approach. The methodology was successfully developed under both batch and continuous flow conditions, and afforded enantiomerically pure

• products with complete stereoselectivity. Substrates bearing electron-donating or electron-withdrawing groups on the aromatic rings provided good to excellent yields, indicating that both types of substituents are well tolerated under the reaction conditions. Although modest yields were obtained under flow

• applications in the preparation of chiral ligands. Keywords: chiral piperazines; electrosynthesis; flow chemistry; green chemistry; imino-pinacol coupling; Introduction Vicinal diamines represent a highly valuable class of compounds that, over the past decades, have found widespread application in natural

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

• would be detrimental: malononitrile is a solid and the rapid formation of solid product BMN often results in a thick sludge that hinders the flow of the reaction solution. Additionally, we were concerned that the lack of solvent, would mean that the MOF catalyst would not be completely submerged in the

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

• . Further scale-up could be achieved by switching to flow conditions, or designing a continuous tank reactor [27]. Several attempts were made to explore enantioenriched vinyloxazoline 6 as a chiral building block. While additions to the double bond were not successful, vinyloxazoline 6 was found to be a

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

• Industrial & Energy Engineering Group Huanghe Construction Co., Ltd., 7 Yandong Xinlu, Lixia District, Jinan 250000, P. R. China China Construction Industrial & Energy Engineering Group Co., Ltd., Nanjing 210023, P. R. China 10.3762/bjoc.21.132 Abstract Flow chemistry technology has demonstrated significant

• potential in advancing the green transformation of the chemical industry while enhancing inherent process safety. Safety, cost-effectiveness, and operational efficiency serve as pivotal drivers for advancing flow chemistry in nitration processes. This review provides a comprehensive analysis of the

• continuous-flow nitration technology – a process historically recognized as one of the most hazardous industrial operations – focusing on its technological advancements in process design, reaction kinetics characterization, and practical implementation over the past decade. Detailed discussions encompass

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• , and flow chemistry are being harnessed to push the limits of light-driven reactions [36]. Terada and colleagues show in this thematic issue how flow chemistry is used to significantly improve the yield of a π-Lewis acidic metal-catalyzed cyclization–radical addition sequence [37]. Recently, chemists

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• conditioner and a dehumidifier. While drop casting, the sample was kept at ≈20–30 °C to ensure a smooth flow of the solvent over the substrate. After drop casting, all films were subjected to vacuum pumping (typically 0.01 mbar) for about 1 h. Before depositing molecules, freshly cleaved graphite surfaces

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

• its 5- or 6-substituted derivatives with a variety of cyclic, alkyl and branched secondary amines, probing the protocol’s versatility and confirming its potential usefulness. This study provides the basis for the application of the protocol in continuous flow systems, such as a continuous

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

• flow rate of 1 mL/min. MS parameters were as follows: mass range m/z 100–2000, capillary voltage 4.5 kV, nebulizer gas 5.0 bar, dry gas 12.0 L/min, and dry temperature of 220 °C. MS/MS experiments were conducted in auto MS/MS scan mode with no step collision. The raw data file was analysed using

• % MeOH for further 20 minutes at the flow rate of 10 mL /min with a combined running time of 92 min. The MPLC run afforded the following subfractions: FD-1 (1.82 g), FD-2 (1.31 g), FD-3 (0.12 g), FD-4 (0.11 g) and FD-5 (0.10 g). FD-1 (1.82 g) was further purified using an HPLC system equipped with a

• preparative SunFire C18 reversed-phase column (10 µm, 10 × 250 mm) and eluted with 30% H2O/ 70% MeOH followed by a linear gradient elution scheme to 100% MeOH for 30 min at a flow rate of 2 mL/min affording 2 (2.32 mg, tR 15.7 min) and 1 (4.13 mg, tR 25.6 min). The FB fraction (2.3 g) was chromatographed

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

• from esters of functionalised arylacetic acid 5 or 6 and involves two separate protocols: first, a metallacarbene, which undergoes the insertion, is generated from the corresponding diazo precursor formed either in flow via hydrazone oxidation (PS-TsNIK packed column), or in batch mode via diazo

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

• – 4500 V); mass range from m/z 50 to m/z 3000 Da; external calibration with Electrospray Calibrant Solution (Fluka). A syringe injection was used for all acetonitrile solutions (flow rate 3 μL/min). Nitrogen was applied as a dry gas; interface temperature was set at 180 °C. General reaction conditions

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

• applications in the pharmaceutical industry. In addition, innovative synthetic methodologies, including environmentally sustainable approaches [21][22][23], advanced catalytic systems [24][25][26], photocatalysis [27][28][29], and cutting-edge technologies, such as flow chemistry [30][31], have contributed

• the electrophilic triazinedione, releasing DMAP to give ester 15 which reacts with DMAP to afford the active N-acylpyridinium species 16. In addition, N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC·HCl), a common coupling reagent, has been applied for a continuous flow

• scaled up to a gram scale. Uozumi and co-workers (2019) reported a carbonylation under aqueous flow conditions using alkenyl halide 240 to prepare cinnamic acid (7) catalyzed by an amphiphilic polystyrene-poly(ethylene glycol) resin-supported Pd-diphenylphosphine catalyst (cat 6) (Scheme 65A) [31]. Also

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

• recent years on developing new methods for synthesizing organophosphorus compounds [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Developing sustainable and green methods for synthesizing organophosphorus materials is a growing field. Methods based on photocatalysis [36], flow-based

• recent years. Recently, an electrochemical reaction of 2-isocyanobiaryls with diphenylphosphine oxides has been reported by Li et al. [45] using a Mn catalytic system with C(anode)/Pt(cathode) in an undivided cell. Different products were obtained with up to 85% yield in a constant flow for three hours

• the gram-scale preparation of some samples. An electrochemical flow system was used in this method, in which carbon and platinum electrodes were used as the anode and cathode, respectively, at a constant current of 55 mA (Scheme 8). Due to the steric hindrance caused by the tert-butyl group, the

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

• -state structure, two bonds (Ca–O and Si–C) are broken, while a Si–O bond is simultaneously formed, in a concerted step implying a cyclic flow of six electrons in a five-membered ring. The isocyanide Ca–N–C bond angle in TS 11-12 lies between that of 7 and 9. While the replacement step is slow, and hence

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

• analyzed by AE chromatography (Dionex DNAPac PA-100 column; 4 mm × 250 mm) at 80 °C with a flow rate of 1.0 mL/min. A gradient of 25–37.5% B in A in 25.0 minutes was used; Eluent A: 25 mM Tris∙HCl, 10 mM NaClO4, 20% acetonitrile, pH 8.0; eluent B: 25 mM Tris∙HCl, 600 mM NaClO4, 20% acetonitrile, pH 8.0

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

• introduction of –CHF– or –CF2– as a replacement for the ring oxygen, or for one (or more) of the –CH(OH)– groups, or for the anomeric oxygen. The various conformational outcomes that flow from making such modifications are discussed below. It should be noted that introducing fluorine into sugars has many other

• negative fluorine atom and the positively charged C=O+ moiety, and σC–H → σ*C–F hyperconjugation. The fluorine atom thus shields the top face of the oxocarbenium ion, and this has flow-on effects on the rate and stereoselectivity of subsequent glycosylation reactions [139]. Another important rotatable bond

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

• . The prepared samples were injected into the spray chamber using a syringe pump with flow rates of 10 to 40 μL/min. The desolvation gas was adjusted to 15 psi. Other parameters were optimized for maximal abundance of [M + H]+, [M + Na]+, or [M + K]+. High-resolution electron ionization mass spectra

• ) was used. MeCN/MeOH/H2O mixture with 50 mM formic acid and 25 mM diethylamine was used as eluent. A flow rate of 0.5 mL/min was applied and the detection of the respective compounds occurred at 280 nm. Data analysis was carried out with the EZChrom ELITE software (version 3.3.2 SP2, Agilent). Ni(II

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

• ), solvent A: H2O + 0.1% formic acid; solvent B: acetonitrile (ACN) + 0.1% formic acid, gradient: 5% B for 0.5 min, increasing to 100% B in 20 min, maintaining isocratic conditions at 100% B for 10 min, flow = 0.6 mL/min, UV–vis detection 190–600 nm]. Preparative HPLC was achieved at room temperature on an

• 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

• 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