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

• , stirring, heating, and cooling modules for enhanced versatility. In addition, the platform is capable of performing under inert and low-pressure atmospheres, handling separation steps, and pressure sensing for reaction monitoring. Its efficacy and robustness were confirmed through the successful synthesis

• medium for enhancing the optimization of the Buchwald–Hartwig amination intermediate, which is crucial for synthesizing the drug olanzapine [47]. The reactor setup was integrated with spectroscopic and chromatographic in-line analytical tools, enabling real-time monitoring of products and reaction

• , each comprising 650 µL within a slug flow reactor [48]. This innovative system features precise monitoring of the reaction slug through a dedicated array of phase sensors and an algorithm designed for detecting its passage. As a result, the workflow delivers a notable boost in productivity, surpassing

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• was funded by the Youth Innovation Talents Project of Guangdong Universities (natural science) in China (No. 2022KQNCX052), Research and Innovation Team for Wastewater Treatment and Monitoring of Guangdong University of Education (No. 2024KYCXTD016), the quality and reform project of Guangdong

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• bis- and tris-norbornadienyl-substituted benzene derivatives. Photometric monitoring of the irradiation of 1h (A), 1i (B), 1j (C), 1k (D), 1l (E), and 1n (F); λex = 315 nm (1h, 1i, 1k, and 1l) or 340 nm (1j, 1n). Insets: plot of absorption at long-wavelength maximum versus irradiation time t

• . Photometric monitoring of the irradiation of 1i (A) and 1l (B) in the presence of [Ru(phen)3](PF6)2; λex = 520 nm. For clarity, the absorption of the sensitizer has been deducted. Insets: plot of absorption at long-wavelength maximum versus irradiation time t [38]. Photoinduced [2 + 2]-cycloaddition

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• − in the aqueous state at a pH of 7.4 due to its weak acidic nature and high solubility in water (80 mM at 37 °C) [6]. Elevated levels of H2S in groundwater pose high risks to both human health and aquatic ecosystems [7], compelling rigorous monitoring of water sources. Even though sensors for

Photoluminescence color-tuning with polymer-dispersed fluorescent films containing two fluorinated diphenylacetylene-type fluorophores

• Kazuki Kobayashi,
• Shigeyuki Yamada,
• Motohiro Yasui and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2682–2690, doi:10.3762/bjoc.20.225

• clearly indicates that the PL originates from a single fluorophore. Using a 1 wt % PMMA film blended with 1a and 1c in an 80:20 ratio (Figure S2g in Supporting Information File 1), the excitation spectrum obtained by monitoring the long PL wavelength derived from 1c was also in good agreement with the

• EFRET values were 55% and 46%. Both mixtures showed a relatively fast energy transfer, which likely caused the PL of 1f to be the major component. Furthermore, the excitation spectrum obtained by monitoring the long PL wavelength originating from 1f using a 1 wt % PMMA film blended with 1a and 1f in an

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• restricted to the recommended one. The reactions should be monitored continuously, and to be quenched as and when recommended in this section. Prolonged heating without monitoring is not recommended. A picture of the experimental set-up is included in Supporting Information File 1 (Figure S31). Single

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• algorithm for the shell growth of core-shell semiconductor nanoparticles. This involves various unit operations such as phase separation, washing, and continuous in-situ spectral monitoring. Although the process conditions for this reaction system do not have as extensive a literature base for training data

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• thioesters 2 (2a as an example) A mixture of (E)-3-(ethylthio)-1-phenyl-3-(phenylamino)prop-2-en-1-one (1a, 70.8 mg, 0.25 mmol) and DBSA (87.9 mg, 0.25 mmol) in water (2 mL) was stirred at reflux in an oil bath under air for 5 h until 1a was completely consumed, as confirmed by TLC monitoring. Then, the pH

• water (2 mL) was stirred at reflux in an oil bath under air for 24 h until 1a was completely consumed, as confirmed by TLC monitoring. Then, the pH value of the reaction mixture was adjusted to neutral using a 10% CH3COOH solution, and the reaction mixture was extracted with CH2Cl2 (3 × 20 mL). The

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• atmosphere. The flask was cooled to 0 ºC, and stirred vigorously after that n-BuBr (11.30 mL, 105.12 mmol) was slowly added to the RB-flask, and the mixture was stirred for 24 h at room temperature (rt), until the reaction completed (TLC monitoring). Then the reaction mixture was quenched with water, and the

• different equivalents (2 equiv for 12, 6 equiv for 15 and 9 equiv for 17) at 0 °C under N2 atmosphere. The red reaction mixture was stirred for 30 min at 0 °C, and further stirred at room temperature for 1 to 6 hours. After the reaction completion (TLC monitoring), the mixture was poured gradually into

• , 18) for 8 h. After the reaction completion (TLC monitoring), excess of triethylamine (TEA) was added to quench the reaction mixture. After the removal of the unreacted pyrrole in vacuo (the temperature of the water bath and the pressure were set to 80 °C and 80 mbar, respectively), the dark brown

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• ) sample the glycan conformational space; ii) investigate how the glycan behaves in a solution (if the MD is performed in explicit solvent), describing carbohydrate–water interactions; iii) monitoring the intramolecular interactions. Usually, this information has to be further validated by performing

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• Information Supporting Information File 5: Experimental details, supporting figures, and copies of spectra. Supporting Information File 6: Monitoring of DA11 under visible-light irradiation. Supporting Information File 7: Monitoring of DA7 under visible-light irradiation. Supporting Information File 8

• : Monitoring of DA6 under visible-light irradiation. Acknowledgements We acknowledge the technical support from UCEA and ULS of PolyU. All authors sincerely appreciate Prof. Dr. Takanori Fukushima (Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology) for

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• (1.0 equiv) in anhydrous DMF (≈3.5 mL per mmol) was added K2CO3 (2.0–4 equiv) and BocNHCH2CH2Br (1.5–4 equiv), then stirred overnight at 60 °C. After the reaction was completed (TLC monitoring), the mixture was evaporated to dryness under reduced pressure. The residue was dissolved in EtOAc

• compound in anhydrous MeOH (≈10 mL per mmol) was added dropwise AcCl (1.0–3.0 equiv) at 0 °C, slowly warmed to rt, and stirred overnight. After the reaction was completed (TLC monitoring), the mixture was evaporated to dryness under reduced pressure. The residue was dissolved in MeOH, acetone was added

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• dissolved in DCM (10 mL), FeCl3 (30 mol %) added and magnetically stirred at room temperature. Within 2–30 h, the reactions went to completion (TLC monitoring), affording, at last, N,O-aminals 5a–r (42–82%) and the corresponding hemiaminals 6a–p (4–35%) after column chromatography (Scheme 3). An increased

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• determine the ISC quantum yield, ΦISC, using the well-studied photosensitizer [Ru(bpy)3]Cl2 (Rubpy) as reference for actinometry [78][79][80]. This approach involved employing identical excitation conditions at 355 nm (Figure 4A) and monitoring the GSB of Rubpy with a literature-reported difference

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• resulting DNA hairpin. The β-anomer of Va was introduced instead of the target dC in the DNA hairpin with TTC loop and tested in the 1H NMR-based assay monitoring A3A-catalysed deamination of dC hairpin (T(GC)2TTC(GC)2T, wherein C is deaminated) at a 150 mM salt concentration at pH 7.4. Recently, FdZ (IId

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• be beneficial to the yield. Finally, by monitoring the reaction time, it was discovered that reducing the reaction time to 1 h further improved the yield to 62%. Finally, using the optimized conditions (Table 1, entry13), the scope was carried out and afforded the desired products 5a–t (Scheme 5

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• ]. The discovery of the nnlA gene resulted from screening a JS1663 genomic library by monitoring for E. coli transformants that produced nitrite (NO2−) in the presence of NNG. Analysis of the mass balance via in vitro experiments showed that NnlA degraded NNG into NO2−, ammonium (NH4+), and glyoxylate

• degradation was unrelated to E. coli being unable to uptake 2-NAE, in vitro experiments with purified, reduced Vs NnlA incubated with 2 mM 2-NAE at pH 7.5 were performed. The LC–MS EICs monitoring 2-NAE (m/z 105.03 ± 100 ppm) show the prominent peak characteristic for 2-NAE. The intensity of this peak does

• (160 μM), Ms (38 μM), and Ps (28 μM). Representative LC–MS EICs monitoring molecular anions of NNG (m/z 119.01 ± 100 ppm) and glyoxylate (m/z 72.99 ± 100 ppm) in samples containing 350 μM NNG, 10 μM dithionite, and 5 μM of indicated NnlA homolog. Samples were incubated for approximately one hour at 21

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• dependence (higher temperature results in higher rates). In 1966, Brown and co-worker reported a specialized apparatus enabling the monitoring and control of HCl gas consumption during the reaction [40]. They observed full conversion of α-methylstyrene (11) within minutes and suggested that the

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• chromatography, with methanol as the mobile phase. After monitoring the fractions by a CAS assay, the positive fractions were concentrated and purified by semi-preparative HPLC on a Cosmosil 5C18-MS-II column (10 mm ID × 250 mm, Nacalai Tesque), using a gradient system with MeCN/H2O (3:7 to 7:3) as the mobile

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• reactant 4, which has a larger energy gap between its HOMO and LUMO of Li+@C60 (1.92 eV). All reactions were conducted in the dark to avoid photoinduced SET reactions (Scheme 2). First, the reactivity was assessed by monitoring the reaction progress using a previously developed electrolyte-added HPLC

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• that enables monitoring by circular dichroism. Upon the addition of Ca(II), a large increase in the binding affinity for halide ions was observed due to the folding of the receptor in a helicoidal form that enabled cooperative interaction with both urea moieties. More flexible coordination responsive

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• stability. Conversely, selenepine 28c and selenepine Se-oxide 29c were quantitatively converted into the seco-HBC 31 by thermal activation at 200 °C for 5 min, as evidenced by UV–visible absorption and HPLC monitoring. SO-extrusion from thiepine S-oxide 29b was also successfully triggered in the solid state

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• 1:1 (Scheme 2). Complex 9 is insoluble in most organic solvents, but it turned out to be unstable in DMSO-d6 solution, as evidenced by monitoring its 1Н NMR spectra (Supporting Information File 1, Figure S1). Figure S1a shows the spectrum of the starting quinoline 5, Figure S1b represents complex 9

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• design allows easy monitoring the reaction course and correct estimation of time required for the reaction to complete. The use of excess of a sialyl donor is quite a common practice; in such cases, higher yields of glycosylation products are usually obtained in line with general consensus that the

• dried at 80 °C in vacuo (0.1 Torr, 1 h)) was added. The mixture was stirred at room temperature (≈20 °C) until complete consumption of the starting material (TLC monitoring, Rf = 0.10 (7), Rf = 0.57 (2), benzene/EtOAc 9:1). The reaction mixture was concentrated under reduced pressure, the residue was

• complete consumption of the starting material (TLC monitoring, Rf = 0.10 (5), Rf = 0.49 (6), EtOAc/petroleum ether 35:65). Saturated aqueous NaHCO3 (5 mL) was added, and the mixture was well shaken and then allowed to warm to ≈20 °C, diluted with CH2Cl2 (50 mL), washed with water (100 mL), 1 M aqueous