Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• literature. During our attempt to scale up the preparation of BPP 2 through the "DPEX" reaction, we unexpectedly obtained a 5-isopropoxy-substituted derivative of BPP (BPP-OiPr 3) (Scheme 1), whose structure was proven by NMR, mass spectrometry, and X-ray crystallography. In this work, we optimized the

• consisting of four molecules, every two of them are stacked with the plane-to-plane distance of 3.45 Å (Figure 1c), displaying a lamellar π–π stacking motif in the overall packing structure (Figure S1 in Supporting Information File 1) [26][27][28][29]. The X-ray structure is well consistent with a model

• micrometers, as demonstrated by SEM. These results provide not only an easy access to highly emissive BPP derivatives with potential as organic fluorescent materials, but also an insight to design derivatives of other PAHs with enhanced fluorescence and charge transfer character. Single crystal structure of

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• and frequency calculations of closed-ring isomers (closed) and transition states (TS) were carried out using Gaussian 16 Rev. C.01 program package. The TS structure was optimized using Opt = TS keyword with Berny algorithm. To obey unrestricted Kohn–Sham solution, the broken-symmetry guess was

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• properties that can modify the activity and pharmacokinetic profiles of drugs [7]. Prominent examples include pantoprazole, a widely used proton-pump inhibitor (PPI) featuring a CF2H group; deracoxib, another drug that also incorporates a CF2H moiety in its structure; and a MET inhibitor specifically

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• structure of 16 was confirmed by serial X-ray crystallography using an X-ray free-electron laser (XFEL) [deposition number CCDC 2352718) [54][55]. We then performed a Strecker-type reaction on the aldehyde 16 to construct an α-aminonitrile 17. To our delight, the key intermediate, 2,3-diaminobenzofuran 11

• a fluorescent intermediate 18, and subsequent ring opening allowed a streamlined one-pot access to the substructure of THIQ alkaloids 14 in a good yield of 60% from 11. The structure of the resulting 14 was elucidated through comprehensive two-dimensional NMR spectroscopy, complemented by NOE

• Strecker reaction and cyclization to form the 2,3-diaminobenzofuran moiety, and gold(I)-promoted cascade sequence via 6-endo hydroamination, spontaneous dehydrogenative oxidation followed by ring opening. Carbon numbering was assigned in accordance with natural products. The structure of 16 was determined

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• structure was obtained, revealing certain geometrical features. Keywords: 2-amino-substituted heterocycles; cyanoacetamide; Gewald reaction; multicomponent reaction (MCR); pyrimidine; Introduction The term “net-zero carbon” is becoming increasingly common as we consider a future marked by a rising global

• was observed at an average wavelength of 384 nm for 5a–e, 439 nm for 6a–e and 430 nm for 7a–e (see Supporting Information File 1 for detailed information). In support of the proposed scaffold 7b, we were able to solve its crystal structure (Figure 3). An intermolecular bifurcated hydrogen bond network

• pyrimidine scaffold. Representative fluorescence spectrum of compounds 5b (λex = 330 nm) and 6e (λex = 430 nm) at 0.2 M in DMSO. Molecular geometry observed within the crystal structure of compound 7b (CCDC 2376493). Strategies towards targeted adducts: A) Niementowski quinazoline synthesis utilizing

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• of noncovalent interactions that work independently from each other [5][6][7][8]. Generating such motifs with orthogonal propensity is appealing not only for the construction of supramolecular polymers with the ability to modulate their structure and properties in multiple ways through adjustment of

• , particularly π-stacking interactions between the aromatic rings in a parallel fashion from both host and guest, which is demonstrated by the crystal structure of the key element of the recognition motif. Results and Discussion Backdrop for design considerations Our interest in macrocycle-mediated

• structure would also be found in the solid state. Fortunately, single crystals of the complex H1 ⊃ G1 were obtained by slow evaporation of chloroform/acetone solvent (1:1, v/v) into a small amount of methanol over the course of two weeks. Indeed, analysis of the crystal structure of the complex revealed a

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• copper-coordinated azomethine ylide 39. Subsequently, the chiral products 35–37 are produced through the reaction between the metalated azomethine ylide 39 and the quinone intermediate 38. The reaction pathway, either 1,4-addition or 1,6-addition, depends on the structure of the hydroquinone 34. The less

• of analogous substrates demonstrates that a bidentate nitrogen structure and a free N–H group are essential for this transformation. The catalytic cycle begins with the coordination of 8-aminoquinoline 71 to Cu(II) catalyst 74, providing an arylcopper complex 76 (Figure 13). This is followed by a

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• corresponding saturated compounds. Subsequent nucleophilic addition of the cyclic vinyl ether to the iminium salt generates an intermediate XXI susceptible of intramolecular electrophilic attack to give a tricyclic structure XXII. The final deprotonation provides the desired product 24. The multicomponent

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• acids feature as the most prolific catalytic structure. The last part of the article discusses hydrogen-bond-donating catalysts and other catalyst motifs such as phase-transfer catalysts. Keywords: asymmetric organocatalysis; atropoisomers; atroposelective synthesis; axial chirality; stereogenic axis

• intermediate Int-53. Control experiments confirmed that this structure could undergo successive reduction and oxidation through intermediate Int-54 to give benzylimine intermediate Int-55. Alternatively, a direct [1,5]-H migration of Int-53 also leads to Int-55. The stereoselectivity of the product is

• astounding enantioselectivities. Both, light and organocatalyst proved crucial for the reaction. The photochemical aspect isomerizes the double bond to (Z)-configuration, and CPA stabilizes the structure whilst mediating the cyclization. The wavelength of 405 nm was chosen so that only the starting material

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• yield and low polydispersity index (PDI), crucial for effective self-assembly [29]. Previous studies on PEG-PS vesicles demonstrated a solvent-exchange method for vesicle formation, followed by a shape transformation induced by osmotic pressure from PEG addition [18]. The structure was then frozen by

•  1, Figure S21). For the shape transformation experiments only the vesicles assembled in DMF were used. To validate the structure of the self-assembly, cryo-TEM was conducted, revealing that the obtained vesicles exhibited a wrinkled appearance, differing from the typically round vesicles observed in

• . However, when the membrane gets too stiff, the deformation is prevented regardless of the increased force that is applied. For further affirmation of the mechanism circular dichroism (CD) spectroscopy was employed to give more insight on the morphological changes in the polymers secondary structure

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

• of suggested optimization results. Through an examination of methodologies, algorithms, and various case studies, this article offers our perspective on the state-of-the-art techniques for optimizing the synthesis of organic molecules, highlighting both challenges and prospects. The structure of this

• conventional photopolymerization reactions but also helps to identify structure–property relationships for copolymer libraries. We have generated a segmented flow pattern (Figure 3b) by alternating the infusion of organic components and degassed water to create nine different compositions [53]. The organic

• 16 microreactors capable of executing diverse conditions in parallel, including photochemistry. The temperature of the capillary reactors can be controlled independently, providing flexibility in experimentation. The reservoir-type distributor, featuring a baffle structure, not only ensures uniform

Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• methods that underlie modern glycobioinformatics approaches [15]. Validation of glycoprotein structure is an important aspect of contemporary structural biology, and Dialpuri et al. present the Privateer database to allow for facile quality control of such structures [16]. Finally, Barillot et al. bridge

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• recently showed that polymerizing negatively curved polycyclic arenes produced an amorphous covalent network. This network was able to mimic the structure and function of carbon schwarzites, serving as an anode material in lithium-ion batteries with high capacity [21]. Further exploration of bottom-up

•  1) featuring three heptagons and two pentagons, with its structure confirmed by X-ray crystallography. This π-expansion approach of compound 1 differs from the method reported by Müllen and co-workers, which involves Ramirez olefination and Suzuki coupling, resulting in the expansion of a seven

• Scholl reaction conditions. The structure of 3 was confirmed with single crystal X-ray crystallography, as detailed later. In addition, another product with a molecular ion peak of 1695.9115 in the high-resolution mass spectrum (Supporting Information File 1, Figure S6) was isolated in trace amounts

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

• HRMS spectrometry were in full agreement with the expected structures, and single-crystal X-ray diffraction analysis was conducted to confirm the structure of compound 7-H. Moreover, the photophysical properties of these PhFlOP derivatives were determined by UV–vis absorption and photoluminescence

• ]. Compared to the traditional PO-containing moieties, PhFlOP possesses an enhanced rigid structure to reduce the possibility of nonradiative decay processes, which would improve optoelectronic properties [17][27]. Thermally activated delayed fluorescence (TADF) materials and devices have emerged rapidly in

• 2–7 was performed by NMR spectroscopy, which confirmed the synthetic outcomes (Figures S1–S11, Supporting Information File 1). The structures of compounds 7 were further confirmed by HRMS and IR analyses (Figures S12–S18, Supporting Information File 1). In addition, the chemical structure of 7-H was

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• benziodoxolone, 2d) were obtained with quantitative yields, as white solids on the gram-scale, easy to manipulate and long-term stable below 0 °C. Crystals of compound 2d were successfully obtained and its molecular structure was confirmed through single-crystal X-ray diffraction. The X-ray analysis revealed a

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• derivatives and the antiparallel stacking mode into columnar structures stabilized by arene–perfluoroarene intermolecular interactions were confirmed by the single-crystal structure of the alkoxy-free side chain analog, i.e., 1,2,4-trifluoro-3-(perfluorophenyl)triphenylene (F). UV–vis absorption and

• analysis (Figures S1–S32, Supporting Information File 1), and all the results agree with the proposed molecular structures. Single-crystal structure of F Suitable single crystals of compound F for X-ray analysis were obtained by slow evaporation of an ethyl acetate/ethanol solution (Figure 2, and

• Supporting Information File 1, Figures S33, S34 and Tables S1–S3). The crystal structure unequivocally confirms that the reaction pattern between 2Li-BP and perfluorobiphenyl, effectively yielded the desired 1,2,4-trifluoro-3-(perfluorophenyl)triphenylene and that the annulation occurred at the expected

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• fused structure toward a phenanthroline diamide (Phen-2,9-diamide) [23] can be achieved by employing a palladium-catalyzed intramolecular C–H arylation [24][25][26][27][28]. One of the thus obtained products exhibited a remarkable extraction performance for a lanthanide ion, in which a metal-specific

• arylation precursors 1a–c. Palladium-catalyzed intramolecular direct arylation for synthesizing 8a and 8b and the X-ray crystallographic structure of 8a. Studies on the reaction conditions for 2a from 1a. Pd-catalyzed C–H arylation of heteroarenes. Supporting Information Accession code CCDC 2227450

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• materials [1][2]. Due to their importance, different synthetic routes involving stoichiometric and catalytic approaches have been developed. The α,β-unsaturated imines, also known as conjugated imines or 1-azadienes, are useful precursors for the construction of aza-heterocycles. Due to their structure

• construction of carbon–carbon bonds [5][6][7][8][9][10]. The hetero-Diels–Alder reaction is therefore an attractive strategy for the synthesis of heterocyclic compounds. It involves the reaction of dienes or dienophiles which possess a heteroatom in their structure. In this reaction, the HOMO of the diene and

• the field, other dienes bearing two nitrogen atoms in their structure such as 1,3-azadienes or azo-alkenes are also included. On the contrary, asymmetric cyclizations involving aza-ortho-quinone intermediates and in situ-formed 1-azadienes were excluded as they have been discussed in other recent

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• /bjoc.20.267 Abstract A new psammaplysin derivative, ceratinadin G (1), was obtained from the Okinawan marine sponge Pseudoceratina sp., and the gross structure was clarified through spectroscopic and spectrometric analyses. The absolute configuration of compound 1 was established by comparing its NMR

• , H-1/C-3, H-1/C-6, H2-5/C-3, H2-5/C-4, H2-5/C-6, H-5a/C-7, H-7/C-8, and 3-OCH3/C-3) supported the presence of the 8,10-dibromo-9-methoxy-1,6-dioxa-2-azaspiro[4.6]undeca-2,7,9-trien-4-ol unit (partial structure a in Figure 2). While the existence of the 11-N-methylmoloka'iamine unit (partial structure

• were linked via a carbonyl group at C-9. Therefore, the gross structure of 1 was elucidated. The absolute configuration of ceratinadin G (1) was assigned by comparing its NMR and ECD data with those of psammaplysin F (2), whose absolute configuration has already been established [10][11][12]. The NMR

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• describe the large-scale extraction, isolation, and structure elucidation of four new metabolites, ianthelliformisamines D–G (4–7). Additionally, we report the isolation of the known natural products, aplysterol (8) and ianthelliformisamines A–C (1–3). Owing to the novelty of ianthelliformisamine D (4) we

• from the amide proton linked the propyl-2-pyrrolidine moiety to the brominated acrylamide fragment and thus the full chemical structure of 4 was elucidated and assigned to ianthelliformisamine D. A refined literature search using Scifinder Scholar [16] revealed that compound 4 contains a novel scaffold

• [18], thus enabling the full chemical structure of ianthelliformisamine F to be determined. The TFA salt of ianthelliformisamine G (7) was also purified as a stable brown gum. In a similar manner to compound 6, the LRESIMS indicated the presence of two bromine atoms; these data also indicated that 7

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• from isoxazole 1a and primary and secondary amines according to the conditions described in entries 9 and 10 in Table 2, with yields of up to 78% (Scheme 4). An experiment with benzylamine and isoxazole 1a on a 1.5 mmol scale gave diamide 10a in 84% yield. The structure of compound 10h was confirmed by

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• stabilizes their secondary structure and their metabolic stability, which is useful for numerous applications [3][4][5]. Indeed, the cyclic structure considerably reduces the number of possible rotational conformers, allowing a rational control of the 3D conformational space. Among these cyclic structures

• tetrahydropyridazine scaffold is also found in numerous natural linear or cyclic peptides such as svetamycins or antrimycins as dehydropiperazic acid (Figure 2) [10]. Whereas many publications have been devoted to the synthesis and structure of piperazic acid derivatives (dehydro, chloro, hydroxy, …) [11][12], nothing

• configuration of compounds 7e and 7e’ and consequently of tripeptides 8e and 8e’ (see Supporting Information File 1). Next, some preliminary conformational studies were performed. Firstly, the X-ray crystallographic analysis of compound 8f did not show any hydrogen-bond pattern and the global structure of the

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• , nucleic acids, polysaccharides, and lipids. These modifications can impact the structure and biological functions of these molecules, ultimately leading to neuronal death, as observed in conditions like AD [30][31]. Recent studies highlight OS as an early event in AD pathogenesis, and mitochondria

• improved biological activities. Employing this approach, Kushwaha et al. [34] synthesized a series of compounds containing benzofuran, tetrazole, and pyrazole within a single structure (Scheme 2). Benzofurans and tetrazole pharmacophores have demonstrated potential anti-Alzheimer activity by inhibiting

• , among others. Ugi reaction: The D2 dopamine receptor (DRD2) is the target of different drugs, including antipsychotics, antiparkinsonian agents, and addiction-related disorders. Aripiprazole and cariprazine are prototypes of newer antipsychotic drugs with a bitopic ligand structure, which includes both

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• initial measurement of 3 at 90 K revealed an unusually large unit cell (a = 7.14 Å, b = 21.38 Å, and c = 44.04 Å). Following structure solution and refinement [76], we found that 3 crystallizes in an orthorhombic space group P212121 with five symmetry independent moieties (Z' = 5) and with no solvent

• , we confirmed that a phase transition had occurred following structure determination at 240 K [78][79]. The X-ray data revealed that 3 crystallizes in the centrosymmetric orthorhombic space group Pnma in the high temperature phase (HTP) with cell axes a = 21.56 Å, b = 8.95 Å, and c = 7.28 Å, in

• temperature, it was rapidly cooled to 100 K under a stream of N2 and the larger, disordered cell was observed once more [80]. (These observations also prompted us to measure a structure of 2 at 240 K; in this case, the unit cell is virtually identical at both high and low temperatures, indicating no phase

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• pyrrolidine intermediates A can undergo further transformations (Scheme 10), depending on their structure and the iodane reagent being used. For example, higher yields of 3-fluoropiperidine products 6 were observed when using cyclic iodane reagents 21 and 22 (Scheme 10), which was suggested to be because a