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

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• structure on the potential energy surface is located, which can be done straightforwardly using standard optimization algorithms. While the use of intermediate energies provides a computationally efficient alternative to explicit transition state searches, it rests on the assumption that there is a

• the potential to significantly accelerate the discovery and optimization of new synthetic routes, thereby impacting materials science and medicinal chemistry by facilitating the synthesis of novel compounds with high precision and efficiency. Pattern Matching Tomberg et al. [9] assembled a look-up

• in Figure 1. Using this approximation the generation and optimization of structures simplifies greatly. In an automatized workflow, all unique and possible combinations of C–H bonds and ortho-directing groups (heteroatom with lone pair) in the substrate are found following this procedure: 1. All

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

• -aromatization. Optimization of IMDA and re-aromatization reactions for the preparation of 8a. Supporting Information Supporting Information File 50: General reaction procedures, compound characterization data, and copies of NMR spectra. Conflict of Interest The authors declare no competing financial interest.

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• -substituted acrylic acid 51 (Scheme 7). After optimization, the iridium complex (Ra)-50, in the presence of cesium carbonate, was identified as the most efficient catalyst, producing compound 52 in 97% yield with an enantiomeric excess of 97.6%. Subsequently, compound 52 was treated with Meldrum’s acid in the

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

• mechanism. Gram-scale synthesis. Optimization of reaction conditions.a Supporting Information Supporting Information File 24: Analytic data and copies of 1H and 13C NMR spectra of compounds 1 and 3, copies of HRMS spectra of unknown compound 3 and copies of HLPC profiles of compounds 3. Funding This

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

• sustainable approaches. Given the widespread incorporation of the cinnamic acid framework in various therapeutic agents, this review delivers critical insights into a molecular design for hit-to-lead optimization, offering detailed synthetic strategies for diverse functional modifications. By critically

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• . The chiral amides (aR)-(−)-6 and (−)-7 were evaluated as ligands in Pd-catalyzed asymmetric allylic amination, and while (−)-7 exhibited promising enantioselectivity, its yield was lower than (aR)-(−)-6. Further optimization of reaction conditions led to improved yields and enantioselectivities up to

• )-(−)-6 as a chiral ligand: The reaction was carried out at 0.1 mmol scale; yields refer to isolated yields. Transformation of the reaction product (S)-13a: The reaction was carried out at 0.1 mmol scale and the yield refers to the isolated yield. Optimization of conditions for the Pd-catalyzed asymmetric

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• /hydroamination reaction. Synthesis of 4a–m. Conditions: Pd(OAc)2 (5 mol %), DPEphos (5 mol %), K3PO4 (3 equiv), DMA, 100 °C, 15 h. Yields of isolated products. Optimization of the synthesis of 4a. Photophysical data of 4a, 4j, 4k, 4l, and 4m in dichloromethane (c = 1·10−5 M) at 20 °C. Supporting Information

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• elegant [2 + 3] cycloaddition of secondary enecarbamates [28], the extension of this reaction to enamides lacking an N–H group is a notable advancement. After extensive optimization, the chiral dirhodium catalyst cat. 1 was found to be most capable in terms of both stereocontrol and efficiency. The use of

• . Optimization studies identified the tetraphenyl-substituted PyBox ligand L1 as particularly effective in controlling the stereochemistry of the polycyclization, yielding high enantioselectivity for most substrates. As illustrated in Scheme 5, tertiary enamides with a tethered electron-rich arene could undergo

• alkaloids, though it features a truncated cyclopentane rather than the characteristic cyclohexane or cyclohexene. In their optimization studies, the authors found the sequential catalysis of a chiral binol–Ti complex and BF3·Et2O to be the most efficient, providing products 39 in high yields with excellent

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

• ][14]. While first examples of radical emitters in light-emitting diodes (LEDs) only delivered around 12% internal quantum efficiency [7], representing no improvement compared to conventional emitters, optimization of the donor-functionalized TTM radical and of the device geometry quickly allowed

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• there was a weakly basic counter anion with excellent displaceability, such as trifluoroacetate or sulfonate, the nitrenium refused to engage with the pendant alkene, and complex mixtures, presumably containing N-N dimeric products of starting material, were observed. During reaction optimization, we

• examples of amino-sulfonoxylations using tethered nitreniums. Putative reaction mechanism. (A) Scale-up and (B) applications. Optimization results. Structure–reactivity relationship with nitrenium tethers. Examination of sulfonic acid scope. Substrate scope exploration with an emphasis on stereocontrol and

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• 10 was unequivocally determined through X-ray crystallographic analysis (ORTEP drawing, Scheme 4). Further optimization by elevating the reaction temperature did not noticeably alter the ratio of 32 and 33 (Table 1, entries 8 and 9). Moreover, attempts to apply interrupted Nazarov cyclization with

• ). Construction of α-iodoenone 13. Construction of aldehyde 14. Synthesis of the advanced intermediate 10 (in the X ray structure of 10 solvent molecule is omitted for clarity). Optimization of the interrupted Nazarov cyclization.a Supporting Information Deposition number 2406738 contains the supplementary

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• pyrazolo[1,5-a][1,4]diazepine core. aDetermined by 1H NMR spectroscopy analysis of crude reaction mixtures. bIsolated yield. Optimization reactions of the intramolecular post-Ugi heteroannulation.a Supporting Information Deposition Numbers 2410526 (for 16m) and 2441192 (for 17-cis) contain the

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• mechanism for the Cu-catalyzed dimerization of 4,4-dichoro-2-butenoic acid derivatives. a) KOt-Bu-mediated intramolecular cyclization of 9. b) Direct formation of cyclopropane 20 from gem-dichloride 5 using KOt-Bu as base. Optimization studies. Synthesis of densely functionalized (2,2-dichlorovinyl