Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• due to the dominance of surrounding benzenoid rings or the presence of biradical character. As a result, these PAHs despite, possessing formal azulene may exhibit properties typical of benzenoid molecules rather than the characteristic azulene features such as red-shifted absorption, a small HOMO–LUMO

• red solid in only 4% yield. A similar strategy was used by Osborn for the synthesis of isomeric compound 6 (Scheme 1) [32]. In this case, compound 3 was dehydrogenated giving compound 4 which was then reduced to the direct precursor 5. Subsequent oxidation using chloranil yielded cyclohepta[klm]benz[e

• antiaromatic character of the pentagon, in contrast to pristine azulene. This results in a significantly red-shifted optical absorption at 997 nm. Therefore, compound 24 should be considered a formally antiaromatic extended indeno[1,2-b]fluorene, rather than a ‘true’ extended azulene. Similarly, Müllen and co

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• (open circles) isotherms of [3.3.3]_oligo (dark red), [3.3.3]_linear (red), [3.3.3]_branch (orange), [4.3.3]_oligo (purple), [4.3.3]_linear (blue), and [4.3.3]_branch (green). a) CO2 at 298 K and b) N2 at 77 K. Formylation of naphthalene-fused propellanes. Properties of methylene-alternating

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

• carbon atom), and the lowest DG strength if the other two priorities are unambiguous. Figure 2 and Table 1 show examples of the results from running the program with “CCCN(C)C(=O)c1ccc(C(=O)c2ccccc2)cc1” as the input SMILES string. The sites marked with red indicate the predicted reaction sites. The

• resulted in more specific SMARTS patterns matching the DG. For example, Figure 3a shows the result from Tomberg et al. [9], which does not include the carbonyl oxygen in the SMARTS pattern match although the pattern marked in red in Figure 3b is part of the database. This example also highlights that in

• predict the experimentally observed reaction site with 78% accuracy over the whole dataset when using no energy threshold, meaning that only the reaction site corresponding to the lowest-energy complex is predicted to be the reaction centre. In Figure 9A, the predictions, correct (green) or wrong (red

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

• compounds bearing imidazopyridine (red) and isoquinolinone-kind (blue) rings. Transition state analysis of IMDA reactions for 6a, 6j, 6h and 6r. Relative energy diagram for the synthesis of 8a from 6a. GBB-initiated synthesis of imidazopyridine-fused isoquinolinones. GBB reaction and N-acylation for the

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

• strain from the Red Sea (Egypt), further enriching the borrelidin series. A halophilic actinomycete strain (HYJ128) from Jeung-do Island (Shinan-gun, Jeollanamdo, Korea), belonging to the genus Nocardiopsis, inhabits a hypersaline saltern and was found to produce a series of new polyketide-derived

• , tert-butyl hydroperoxide (TBHP), and Ti(OiPr)4, resulting in the desired epoxide 63 with a 90% yield. Regioselective reductive opening of this epoxide was successfully carried out with Red-Al®, yielding diol 79. The more reactive primary alcohol in diol 79 was selectively masked as TBDPS ether 80 (94

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• purified by the Davis group [8]. In vitro antiplasmodial image-based assay Plasmodium falciparum 3D7 were cultured in RPMI1640 (Life Technologies, Camarillo, CA, USA) supplemented with 2.5 mg/mL Albumax II, 5% AB human serum, 25 mM HEPES, and 0.37 mM hypoxanthine. Human red blood cells (RBC) (O+) were

• supplied by Australian Red Cross LifeBlood in accordance with agreement 23-05QLD-23. Use of human RBC for antiplasmodial experimentation was in accordance with Griffith University Human Ethics Exemption Approval #03/08/11019. Ring-stage parasites were treated with compounds following two rounds of sorbitol

• Australian Red Cross LifeBlood for the provision of fresh red blood cells, without which antimalarial testing could not have been performed. Funding The authors acknowledge the Australian Research Council (ARC) for support towards NMR and MS equipment (grants LE0668477, LE140100119, and LE0237908). The

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• . C skyblue, O red, Br brown, Au yellow. (c) Schematic illustration of the mechanism leading to precipitation (named “supramolecular polymerisation” by the authors) after adding various additives to the solution of β-CD and [AuBr4]− anions. Reproduced from [51] (© 2023 H. Wu et al., published by

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• system [12]. In addition to these covalent bonding interactions, additional secondary bonding (e.g., red-dotted bonds between iodine and oxygen in phenylalanine-based hypervalent iodine macrocycle in benzene system in Figure 1A) can arise in these systems from neighboring atom lone pairs. Secondary

• the area of the electrophilic cavity of HIM (shown in red) being smaller, which suggests lower electron density. In contrast, the red areas of the three outwardly projected carbonyl oxygens (formerly the carbonyl of benzoic acid) are larger, demonstrating the higher overall electron density of that

• for marked differences in the arrangement of groups in space. The overlaid image of lithium complexes 2 and 3 (Figure 8) shows the similar arrangement of all groups on plane except for one benzyl ring (highlighted by a red asterisk) in complex 2 that faces outside the interior of the macrocycle. A

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

• oxidation of azolium intermediate 174 under ambient air conditions (Scheme 55). The reduced catalyst red-cat 5 is reoxidized by the co-catalyst Fe(III) phthalocyanine (FePc), closing the catalytic cycle [98]. On the other hand, Syaikh and co-workers (2021) converted cinnamaldehyde (162) into methyl

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

• similar absorption feature, but slightly bathochromically shifted, was observed for the thienyl-substituted derivative 4m. The strongly electron-donating N,N-dimethylaminophenyl group (products 4k,l) resulted in segmentation into two absorption bands accompanied by a strongly red-shifted lower energy

• shift, while the emission band of 4j was slightly red-shifted. The N,N-dimethylaminophenyl-substituted compounds 4k and 4l showed the strongest bathochromic shifts of the emission spectra, which might be due to the occurrence of donor–acceptor interactions between the electron-deficient uracil and the

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

• the molecule remains mostly planar in the excited state [37]. As a result, we observe weak emission in the yellow to red spectrum, because the respective transition remains symmetry forbidden. Circularly polarized photoluminescence PTM has been developed prior to TTM, as the first stable

• the time that they remain in their enantiopure state. The glum as a measure for the strength of CPL is of order 8 × 10−4 for PTM and 5 × 10−4 for TTM. Mixed halide triarylmethyl radicals Substitution of all para-positions in PTM with iodine atoms yields the 3I-PTM radical with a red-shifted emission

• -tribromophenyl units shifts the photoluminescence systematically towards the red (see Figure 2a–c) [50]. The ϕ also decreases systematically, demonstrating that also more pronounced mixed halogenation does not significantly change the symmetry of the locally excited (LE) state. The tris(2,4,6-tribromophenyl

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• 6a, we observed a blue-shifted absorption profile due to the break of the conjugation in sulfur-based acceptors. Compounds 4a and 6a presented a similar absorption profile, while molecule 5a showed a red-shifted spectrum tailing up to the visible region (Figure 2a). The lack of a significant charge

• antiaromatic compound as an acceptor was previously reported (Figure 2) [31]. The dibenzo[b,d]thiophene 5,5-dioxide (5) was chosen for further investigation because of its red-shifted absorption. From a photochemical perspective, this characteristic can facilitate the use of less energetic light sources

• . Analyzing the diverse absorption profiles, we can observe an increase in the red-shifted behavior related to the donor strength in compounds 5e, 5d, and 5c. In contrast, the azepine-derived compounds are the most blue-shifted (Table 1, entry 5). The same trend is observed in the emission (Figure 2b). The

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• colors: green or grey = C, white = H, blue = N, red = O, orange = S, and purple = Cs. For the crystal structure, the overall stoichiometry of Cs+, PO43−, 18-crown-6 and anion receptor is 3:1:3:1. Phosphate anion is encapsulated inside the hexaurea cavity and stabilized by 12 × N–H···O hydrogen bonds

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• ellipsoids at the 30% probability level. The intramolecular hydrogen bond is shown as red dashed line. The bioavailability radar of studied compounds 5a–e. The interactions of potential drugs 5a–c in the active site of enzyme iNOS. The interactions of potential drugs 5d and 5e and control drug (DEX) in the

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• unknown photoisomer (N-UnS1). Structural investigations using exhaustive 2D-correlation NMR spectroscopy were also inconclusive. Next, the push–pull functionalized derivatives O-NBD2 and N-NBD2 were investigated. Notably, N-NBD2 exhibited the most pronounced red shift (Table 1) and was the only nitrogen

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• representation of the superimposed most stable ligand–protein complexes from IFD for E- and Z-6αMan 4 (A: E in red, Z in yellow) and E- and Z-3αMan 5 (B: E in turquoise, Z in magenta), as well as of the EE, ZZ, EZ, and ZE isomers of glycocluster 6βGlc3αMan 1 (C) and of 6αMan3αMan 2 (D). The protein FimH (1UWF

• ) is depicted as ribbon diagram and the ligands are displayed as stick models (glycoclusters 1 and 2: EE: blue; ZZ: violet; EZ: green; ZE: red). Superposition of the isomers shows the similarity of the binding of the terminal mannoside antenna within the FimH CRD and the different orientations of the

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

• with the highest reactivity, they are consistent with ref. [11] and serve as references in this work. Chemical structures of the HBC dye family [7]. Variations to HBC530 highlighted in red color. All dyes shown bind non-covalently to Pepper RNA, a fluorescent light-up aptamer. For one of them (HBC530

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• tube and centrifuged (7200 rpm, 5 min). The supernatant was carefully poured off. Next, the crude solid was dissolved in 1 M NaOH (25 mL) which results in a yellow and then red solution. Afterwards, EtOH (144 mL) was added which gave a white precipitate that was collected by centrifugation (7200 rpm

• ), b) a mixture of C1 (0.5 mM) and Me6PXDA (1.0 mM), c) a mixture of C1 (0.5 mM) and Me6PXDA (0.5 mM), and d) C1 (0.5 mM). Cross-eyed stereoview of the C1·Me6CHDA complex in the crystal. Color code: C, gray; H, white; N, blue; O, red; S, yellow. Cross-eyed stereoview of the crystal packing observed in

• the molecular cell of C1·Me6CHDA. H-atoms are omitted for clarity. N···O distances less than 4.40 Å are indicated with dashed lines. Color code: C, gray; N, blue; O, red; S, yellow. a) Representative plot of DP (μcal s−1) versus time from the titration of C1 (0.1 mM) in the ITC cell with a solution of

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• systematically red-shifted by ca. 3–5 nm compared to those of the corresponding parent phenacenes. The vibrational progressions of the absorption and fluorescence bands were little affected by the fluorination in the solution phase. In the solid state, the absorption band of F8-phenacenes appeared in the similar

• wavelength region for the corresponding parent phenacenes whereas their fluorescence bands markedly red-shifted and broadened. These observations suggest that the intermolecular interactions of excited-state F8-phenacene molecules are significantly different from those of the corresponding parent molecules

• -intensity band at 376–393 nm and a moderate-intensity one at 333–347 nm were observed for all compounds studied. The former and the latter absorption bands are, respectively, assigned to the α- and p-bands according to Clar’s description [50]. The absorption bands only slightly red-shifted upon the π

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

• precipitated product was filtered, washed with H2O (20 mL), and dried in vacuo at 60 °C. The crude material was purified by flash column chromatography (SiO2, 10 → 100% EtOAc in diethyl ether) to yield 7 as a red solid (10.7 g, 12.9 mmol, 78%, 99% purity determined by analytical HPLC). 1H NMR (600 MHz, CDCl3

• chromatography (chloroform/acetone, 3:1) to yield to 11a (2S,4R) (1.18 g, 1.7 mmol, 39%) and 11b (2S,4S) (0.87 g, 1.22 mmol, 29%) as red solids. 11a: 1H NMR (600 MHz, CDCl3) δ 8.86 (s, 1H), 8.00 (d, J = 9.2 Hz, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.62–7.46 (m, 3H), 7.35 (d, J = 8.1 Hz, 1H), 7.30 (d, J = 7.4 Hz, 1H

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• reaction time minimizes this risk by allowing the reaction to proceed quickly and efficiently before damage occurs. To avoid damage caused by high energy wavelength, the use of irradiation in the red region could be considered [62][63][64][65]. Aqueous media: Developing photoredox reactions compatible with

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• 1 (1:1); bottom – receptor 1; the dotted black lines indicate shifts of the proton signals upon complex formation and dotted red lines indicate lack of signal shift. Proposed binding mode of receptor 1 to tripeptide 2. Binding affinities of receptor 1 to amino acids determined by ITC experiments and

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• provides yet another example of the structural flexibility of perfluorobenzylated compounds and their sensitivity towards chemical environment [18]. The molecules are arranged in two distinct columns, colored red and green that are skewed from one another by 31.2°. There is no significant π–π overlap

• at 416 nm is the most red-shifted from ANTH of the listed compounds, resulting in deeper blue fluorescence. It also has the largest Stokes shift of 837 cm−1 (large Stokes shifts are attributed to attenuation of fluorescence by self-quenching processes [30]). Only ANTH obeys the mirror image rule

• stacked columns of ANTH moieties are colored red and green, BnF groups are colored in yellow, and H atoms have been omitted for clarity. In the off-side view (bottom right), both, F and H atoms are omitted for a better overview. Absorption spectra of ANTH and 9,10-ANTH(BnF)2 in CH2Cl2 recorded over the

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• with Grignard reagent, and oxidation with RuCl3/NaIO4. Keywords: aggregation pheromone; chiral 2-methyloxirane; red flour beetle; total synthesis; Introduction The red flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), is a cosmopolitan, destructive stored product pest [1], which

• harmful to human health and this became a significant challenge to food security [6]. Long-term synthetic pesticide applications to control the red flour beetle has resulted in the development of resistance to organophosphates, pyrethroids, methyl carbamates, and neonicotinoids [7][8]. It became critical

• tosylate and a chiral Grignard reagent. The synthetic pheromone could be valuable for the control of the red flour beetle. The aggregation pheromone of Tribolium castaneum. Retrosynthetic analysis of the aggregation pheromone (4R,8R)-1. Synthesis of chiral tosylate (S)-10. Synthesis of chiral tosylate (R

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• diazocine attached to glutamate to form a photoswitchable neurotransmitter [10]. The halogen-substituted N-acetyl diazocines 2–4 were used as the starting compounds for further derivatization via Pd-catalyzed cross-coupling reactions. Solutions of the Z isomers are yellow. The E isomers are red. Synthesis