Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• scaffolds in a highly efficient manner. It was found that brominated azides do not undergo lactamization under the current conditions which presents an opportunity for further optimization of reaction conditions to expand the scope. Experimental General procedure for synthesis of analogs 7 and 8 A solution

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• optimization of promising lead structures has therefore inspired the development of powerful synthetic strategies. A glance at Web of Science reveals that one-pot methods and multicomponent reactions (MCRs) [1] have attracted steadily increasing attention within the scientific community over the past 25 years

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• the reaction selectivity can be directed towards the formation of arylated dienes 10, which would directly contribute to our previous work [26]. Therefore, we performed optimization of the arylation conditions (Table 1) to improve the reaction selectivity towards the aryldiene 10a formation, indicated

• optimization see Supporting Information File 1. Next, we switched to internal N-nucleophiles. N-Nosylated starting material 7f under standard arylation conditions gave the 2-(1-(tert-butyldimethylsilyl)vinyl)-1-((4-nitrophenyl)sulfonyl)pyrrolidine (14) with a 56% yield. Most likely in this case sulfonamide N–H

• . aThe reaction was performed under modified conditions: I-2 (3.0 equiv), 20 h because under standard reaction conditions incomplete conversion was observed (with 48% recovered 16c). Reaction conditions optimization for the arylation of aliphatic chain-containing propargylsilane 7a. Aryldiene scope

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• ester 4. Optimization of conditions to convert diketone 15 into cyclopentanone 14.a Supporting Information Supporting Information File 42: Experimental procedures, characterization data and copies of 1H and 13C NMR spectra. Acknowledgements We thank Prof. Zhen Yang (Peking University) for helpful

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

• reaction and a screening of reaction parameters such as solvents, electrodes materials, electrolytes, total charges, and concentrations of the reaction mixture was performed. All optimization studies were carried out using 0.5 mmol of 1a in the presence of methanesulfonic acid in an undivided cell (5 mL

• comprehensive optimization of the flow reaction conditions was carried out using the model substrate 1a systematically varying key parameters such as the working electrodes, the current intensity, the total charge, the flow rate, and the equivalents of the employed electrolyte. Following this in-depth screening

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• . Plausible reaction mechanism. Optimization of reaction conditions.a Supporting Information Supporting Information File 24: Experimental section, characterization of synthesized compounds, and copies of spectra. Funding P.A.J. gratefully acknowledges the Chhatrapati Shahu Maharaj Research Training and

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• methylide with various arylidene-azolones. First, a series of various arylidene-azolones 1–5 were prepared (Scheme 2). All compounds were created in accordance with our previously published protocols [20][28][29]. Next, optimization of [3 + 2]-cycloaddition reaction condition was performed using derivatives

• . Optimization of the reaction conditionsa. Supporting Information Supporting Information File 22: Experimental part, X-ray data and copies of NMR spectra. Acknowledgements A.A. Korlyukov and A.R. Romanenko are grateful to Ministry of Science and Higher Education of the Russian Federation (Contract No. 075

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

• glycosyl donor, the influence of remote protecting groups on donor reactivity and acceptor nucleophilicity should not be underestimated. This necessitates careful optimization of reaction conditions and the rational selection of compatible donor–acceptor pairs [77]. Protecting groups can also be used to

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

• engaged in the development of continuous-flow nitration systems. Keywords: continuous-flow; kinetics; nitration; optimization; scale up; Introduction Nitro compounds hold an extremely important position in the field of organic chemistry, mainly because they are easily obtainable and can be converted

• coexist with engineering bottlenecks requiring optimization in process safety and scale-up strategies. Contemporary research endeavors prioritize two synergistic pathways: (i) pioneering alternative nitration pathways via innovative chemical approaches, particularly through novel nitrating agent

• selection and strategic implementation of appropriate methodologies. This is particularly crucial given that the advantages of flow chemistry are not universally applicable across all nitration reactions. Consequently, the optimization of such processes must be carefully tailored to align with the specific

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

• ), 1.15 EPS (2) and Rhizobium leguminosarum bv. viciae VF39 EPS (3). (a) Oak Ridge Thermal Ellipsoid Plot view of the X-ray crystal structure of pyruvylated galactose 6. (b) Hydrogen-bonding in the crystal structure of pyruvylated galactose 6. Synthesis of trisaccharide precursor 14. Optimization of

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 approach where sodium hypophosphite was used as a reducing agent. The reactivity of LiH2PO2, KH2PO2, RbH2PO2, and CsH2PO2 in reductive amination was investigated for the first time (Scheme 1b). Results and Discussion At the initial step, optimization of reductive amination conditions on the

• benchmark reaction between cyclohexanone and morpholine was carried out (full optimization details are provided in Supporting Information File 1). The reaction could proceed in the presence of only H3PO2 furnishing the model product in 70% yield (Table 1, line 1) at 130 °C, for 4 h. To conduct 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

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• reaction carried out in the presence of 5 mol % of NiSO4 gave not only dimer 4, but also the annulation product, compound 3a. Further optimization of the reaction conditions aimed at suppressing the formation of dimer 4 showed that nickel chelates exhibit enhanced selectivity in catalyzing the annulation

• reactions of indoles 9b,c with azirine 2a. Ni(II)- and Cu(I)-catalyzed reactions of indole 15 with azirine 2a. Optimization of 3a synthesis a. Supporting Information Deposition number 2402772 (compound 7) contains the supplementary crystallographic data for this paper. These data are provided free of

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• photocatalyst. Examples of compounds with medicinal effects containing an enaminone structural moiety. Synthesis of enaminones. Substrate scope. Scale-up synthesis of enaminone 9a. Mechanistic studies. Proposed mechanism. Optimization of reaction conditions. Supporting Information Supporting Information File 6

• : Additional optimization details, mechanistic studies, experimental details, characterization data and NMR spectra for enaminones 9. Acknowledgements We would like to thank Prof. Jose Manuel Costa-Fernández for his help with the spectroscopic studies. Funding This work has received financial support from MCI

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• need for safer, non-toxic alternatives. Computational design can play a key role in minimizing trial and error during system development and optimization. Looking even further, utilizing azobenzene protonation in solid matrices can open new opportunities for practical sensing applications. Experimental

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

• , we propose a molecular-level model for the adlayer of the EEE isomer of FNAAP. Based on the experimental lattice parameters, an initial geometry was modelled and subjected to geometry optimization using ReaxFF. The optimized assembly of FNAAP on bilayer graphite is shown in Figure 3c. The

• Quantumwise ATK-classical is devised for geometry optimization. The graphite (previously optimized) was kept fixed during the simulations, and the molecular geometry was fully optimized. Parameter set: ReaxFF-CHO-2008 [32]. A force tolerance of 0.001 eV/Å, stress tolerance of 0.001 eV/Å, and a maximum step

• size 0.01 Å were used for the optimization. The limited memory BFGS (L-BFGS) optimizer method was employed for optimization. L-BFGS is an optimization algorithm in the family of quasi-Newton that approximates the Broyden–Fletcher–Goldfrab–Shanno (BFGS) algorithm using a limited amount of computer

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

• synthesis of benzamides via the arylation of isonitriles with diaryliodonium salts under blue light irradiation (Scheme 1C). Results and Discussion We commenced our investigation by the optimization of the reaction conditions. During the preliminary experiments we tested different solvents and solvent-to

• . Unfortunately, 4CzTPN, 4CzIPN, and 3DPAFIPN did not demonstrate increased efficiency, and the yields of the target product 2aa were slightly lower than for [Ru(bpy)3](PF6)2 (Table 1, entries 4–6). Thus, all further optimization studies were done using [Ru(bpy)3](PF6)2 as a catalyst. After, we moved to the

• using 1,2-dibromoethane as an internal standard. cNot detected by GC–MS. Proposed reaction mechanism. Optimization of the reaction conditions.a Supporting Information Supporting Information File 32: Experimental section, characterization data and control experiments. Acknowledgements Authors

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

• straightforward workup and minimized free copper on solution. Due to this, the catalyst could be regenerated and reused in up to eight cycles. Upon optimization, this practical and versatile method could be used for the synthesis of several benzoxazole derivatives. A Letter was contributed by D’Andrea and Jademyr

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

• × 10−2, respectively), its PLQY was relatively low (24%). Further molecular optimization led to the development of compounds 53a–c, which demonstrated ultra-narrow emission bands (FWHM = 16–34 nm), high PLQYs (67–82%), and exceptional CPL brightness (BCPLs of 583, 374, and 349 M−1 cm−1, respectively

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

• and excited state) were optimized without restrictions, using tight optimization criteria and an ultrafine grid in the computation of two-electron integrals and their derivatives. The true minima were verified by performing frequency calculations in the corresponding environment. The implicit

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

• 3. Conditions: aMethod A: thioamide 1 (1.0 equiv), PhINMs or PhINTs (2a, 1.5–2.0 equiv), 0→24 °C, 6‒60 min. bMethod B: thioamide 1 (1 equiv), aryl sulfonamide (1.2 equiv), PhI(OAc)2 (1.5 equiv), 0→24 °C, 10–30 min. Optimization of the reaction of thioamide 1a with iodonium salts [I]. Supporting

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

• -phenylenediamine and acetone was selected as a model reaction. The optimization of the reaction conditions is summarized in Table 1. All reactions were carried out at room temperature without involving any catalyst or additional solvent. While o-phenylenediamine is solid, it dissolves well in the reactant acetone

• , thus the actual reaction mixture remains in a liquid state, making it ideal for HHP-assisted reactions. The first reaction in the optimization effort was the control experiment at atmospheric pressure. Under these conditions, no product formation was observed even after 10 h reaction time. However, 8

• effect appears to work synergistically with reaction time. The optimization data indicate that the use of HHP resulted in the formation of 1,3-dihydro-2,2-dimethylbenzimidazole (3a) in excellent yield (90%) whereas, in contrast, the ambient pressure reaction did not provide any product. The reaction

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• complex substrates. Crucially, structural optimization of HRP components could potentially overcome current mechanistic limitations, establishing a generalized platform for hydrogen atom transfer (HAT)-enabled direct functionalization. This advanced methodology would demonstrate unprecedented versatility

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• ions, making a significant contribution to synthetic methodology (Scheme 19) [12]. This method was conducted in an undivided cell, using N-methyl-N-phenylacrylamide 1 and sodium trifluoromethanesulfinate (36) as model reactants. Through meticulous optimization of conditions, including catalyst

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

• examples), the average yield of 57% indicates that the process might require optimization, in particular, for further methodological implementation. Here, we report on the improved synthesis of (hetero)aroyl-S,N-ketene acetals 8 by careful solvent and temperature optimization. Results and Discussion The

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

• phosphorylation of enol acetates. Optimization of reaction conditions for the synthesis of β-ketophosphonate 3a from enol acetate 1a and diisopropyl H-phosphonate (2a)a. Supporting Information Supporting Information File 4: Experimental details, compound characterization data, and NMR spectra. Funding This work