Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• regioselectivity (Figure 4). In the protonated intermediate 12 derived from epoxide 9a, the carbon atom preferentially attacked by chloride bears a relatively more positive charge, which is consistent with an electronically favoured nucleophilic attack. In contrast, for the protonated intermediate 15 derived from

• epoxide 9b, the more positively charged epoxide carbon is sterically shielded by the neighbouring ester carbonyl group. As a result, nucleophilic attack occurs at the sterically more accessible, albeit less positively charged, epoxide carbon. These observations indicate that the regioselectivity of

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• careful analysis of the 2D NMR spectra (HSQC, HMBC) all carbon signals of both isomers could be unambiguously assigned to the corresponding atoms (Table 2). This clearly shows that the data given in literature [4] must be corrected. Oxidation of melifoliones Mixtures of melifolione A (1) and melifolione B

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• their 2,5-positions through sp3-hybridized meso-carbon atoms [10]. The ability of CPs to selectively bind anions [11], cations, ion pairs and neutral guest species, combined with the versatility to introduce diverse functional groups, has enabled the fabrication of calix[4]pyrrole-based supramolecular

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• active site [17]. Hence, we decided to functionalize this position with an alkyl linker consisting of 9 carbon atoms to mitigate any steric clashes between the HDAC inhibitor and the nanogold particle, which could be detrimental to the probe binding affinity (Figure 1). Further to this, we previously

• clearly visualized in association with the CoREST complex by cryo-EM; however, its absence in side-view 2D classes prevented precise localization of the HDAC catalytic domain. We speculate that the flexibility of the 9-carbon alkyl linker, and additional flexible linker to the nanogold particles, may have

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• reference to 13C NMR signals of the starting material 12, the 13C NMR spectrum of compound 7 exhibits four additional aromatic carbon resonances, which are consistent with the phenyl ring carbons of phenyl selanyl function tethered to the naphthalimide core. The signal at 142 ppm is assigned to the ipso

• carbon directly attached to the selenium atom. The resonance observed at 136 ppm corresponds to the chemically equivalent ortho carbons. The meta carbons appear as a single signal at 130 ppm, while the para carbon is observed at 127 ppm. The reduced number of aromatic signals arises from the chemical

• equivalence of the ortho and meta carbon pairs, confirming the proposed structure. In contrast, with reference to the 13C NMR signals of starting material 12, compound 8 exhibited eight new 13C NMR peaks in the aliphatic region (14–32 ppm), which is attributed to the incorporation of an octyl selenide unit

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• %) with the calculated values. The carbon and hydrogen contents were determined using the Pregl gravimetric method, nitrogen by using Dumas' gasometric micromethod, and chlorine by the mercurimetric method. N-Methyl-ᴅ-glucamine and (−)-cytisine ((1R,5S)-1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido[1,2-a

Non-central chirality in organic chemistry

• Ken Tanaka and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2026, 22, 370–371, doi:10.3762/bjoc.22.24

• ; chiroptical properties; molecular chirality; Chirality is a foundational concept in organic chemistry, traditionally framed around tetrahedral carbon stereocenters. Over the past decades, however, it has become increasingly clear that molecular handedness is not confined to localized points in space. Axes

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• substituents on the nitrogen (e.g., tosyl, carbamate, or acyl groups) distorts the planarity of the amide and diminishes amidic conjugation (Scheme 1b). These “twisted” amides exhibit a dramatically enhanced electrophilicity at the carbonyl carbon and a significantly weaker C–N bond strength [28][29][30][31

• of CeO2 to attack the carbonyl carbon, leading to cleavage of the C–N bond (B). Subsequent nucleophilic attack of the octoxide anion on the activated carbonyl center (C) then furnishes the ester product. Later, the same group found that niobium could also serve as a heterogeneous Lewis acid catalyst

• hydrogen chloride acting as a Lewis acid, enabling nucleophilic attack by the amine to form a tetrahedral intermediate Z. Subsequent intramolecular hydrogen shift, followed by elimination of dimethylamine, affords the protonated transamidation product. In 2021, Lee et al. discovered that carbon dioxide

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• . This review aims to explore intriguing examples of such ring-size alterations in all aspects of terpenoid synthesis. The current state-of-the-art regarding proposed biosynthetic pathways for terpenoids with unusual carbon skeleta, occurring either during initial cyclisation or subsequent oxidative

• these puzzling questions or even result in reassignment of the molecular structure [6][7][8][9][10]. Nevertheless, terpenoids with novel or highly uncommon carbon skeleta continue to attract interest from both biologists and chemists, as they often possess interesting biological properties owing to

• secured. Organic synthetic chemistry can help to fill gaps or evaluate, support or revise initially implausible proposed biogenesis routes by attempting to mimic these transformations (= bioinspired or biomimetic synthesis) [11][12][13][14][15][16][17][18]. In general, the biogenesis of unique carbon

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• -adducts 4a–e, the carbon signals of ring A (Figure 1) appear at δC 44.8–45.0 ppm (CH21), 27.3 ppm (CH22), and 25.2 ppm (CH23). Ring B carbons resonate at δC 67.7–67.8 ppm (CH4), 46.3–46.4 ppm (CH5), and 58.2–58.3 ppm (CH6). The carbonyl carbons of ring C and the barbiturate ring appear at δC 150.0, 169.3

• –169.4, 171.2–171.5, 175.5–176.8, and 176.4–177.9 ppm. The spiro carbon appears at δC 70.1–70.3 ppm. For diastereomers 4f–p, the 13C NMR spectra proved more informative than the 1H NMR spectra, clearly displaying a duplicate set of nearly all signals. The chemical shifts of carbons in rings A, B, and C

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• molecular structure and reactivity, yet it cannot be measured directly [4]. This inherent elusiveness contributed to decades of debate over the structure of benzene, the prototypical aromatic molecule, until August Kekulé proposed his venerable representation: a six-membered carbon ring with alternating

• single and double bonds (Figure 1A) [5]. However, despite its strength in representing a planar cyclic arrangement of tetravalent carbon atoms, this formalism fails to accurately depict the observed reactivity, structure, and stability of benzene. It implies three rapidly equilibrating, localized double

• the W(0) center was also found to promote the retro-Diels–Alder process, effecting the formal extrusion of acetylene and generating modified arenes. This transformation thus represents both a rare example of a Diels–Alder reaction of benzenes and a remarkable two-carbon molecular editing of the

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• represent thermodynamically favored, more stable products formed upon prolonged heating. To support the hypothesis that the carbonyl carbon atom in pyranoquinoline exhibits higher electrophilicity than in the open-chain ester, quantum chemical calculations were performed to evaluate their electrophilic

• properties (see Supporting Information File 1, pages S3 and S50–S51). The methyl ester was selected as the model open-chain compound. Calculations revealed that the initial atomic charge on the carbonyl carbon in the lactone was +0.234, whereas in the methyl ester it was slightly lower at +0.225. Further

• consistently confirmed the trend: greater electrophilicity is observed for the carbonyl carbon in pyranoquinoline, corroborating the experimental observations. Based on these results, the proposed mechanism of the multicomponent reaction involves initial lactone formation, followed by ring opening

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• phenols [25]. Hocking has described the oxidation of o-hydroxyacetophenone and some benzophenones with an aqueous alkaline hydrogen peroxide solution [26]. The key steps of oxidation of ketones into phenols include: a) nucleophilic addition of the hydroperoxide anion to the carbonyl carbon; b) [1,2]-aryl

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• corresponding to five methyl protons, seven sp3 methylene protons, two sp3 methine protons, two sp2 methine protons, and two hydroxy protons. The connectivity of proton and carbon atoms was assigned from the HMQC spectrum (Table 2). The planar structure of compound 1 was elucidated by a 2D NMR experiment

• III (H-9 (δ 1.58)/H2-11 (δ 2.55, 2.48)). 1H,13C HMBC correlations were then observed from the methyl protons H3-12 (δ 0.89) and H3-13 (δ 0.83) to the sp3 methylene carbon C-3 (δ 41.3), the sp3 quaternary carbon C-4 (δ 32.8), and the sp3 methine carbon C-5 (δ 55.2). Correlations were observed from the

• methyl proton H3-14 (δ 0.91) to the sp3 methylene carbon C-1 (δ 38.4), C-5, the sp3 methine carbon C-9 (δ 51.1), and the sp3 quaternary carbon C-10 (δ 36.5) and from the methyl proton H3-15 (δ 1.15) to the sp3 methylene carbon C-7 (δ 39.5), the oxygenated sp3 quaternary carbon C-8 (δ 77.9), and C-9

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• Å (as a proxy for the replacement by deuterium) [20]. Thus, the calculated isotope effect is the sum of the effects of deuteration of the OH and NH positions. However, as isotope effects are transmitted poorly via aliphatic carbon atoms [18], the effect at the phenolic ring can be assumed to stem

• bond [21]. When measuring 13C NMR spectra in DMSO-d6 containing different D2O/H2O ratios, isotope effects were clearly observed at several positions (Figure 6c and Figure 6d), with a particularly pronounced upfield shift of the phenol ipso-carbon atom (C14, Δδexp = 0.21 ppm). This two-bond isotope

• ) Structure of the truncated model compound used for DFT calculations, with explicit water molecules and hydrogen bonds. b) Structure of 1 indicating formation of IMHB, as well as numbering of all carbon positions. c) Overlay of peaks from the 13C NMR spectra of 1 with varying percentages of D2O/H2O in DMSO

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• its multiple oxidation states and ability to form diverse bonds with carbon, nitrogen, and oxygen. This versatility underpins the pivotal roles of organosulfur compounds in pharmaceuticals, catalysis, and materials science [1][2][3][4]. Among these, sulfilimines (R2S=NR') have attracted growing

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• formation of another structure with increased electron density in conjugated system. Especially, the signal at 5.9 ppm (Hb, green to cyan) can be attributed to a change in aromatic hydrogen to aliphatic. The addition of cyanide to vinyl carbon can explain this change. Upon the addition of 1 equiv of CN

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• by BH+ from the side opposite to the –CH(EWG)2. Thus, only diastereomer III is formed. Deprotonation of this intermediate leads to carbanion IV. For further attack by the carbanion center to the carbon atom bonded to bromine, the –C(EWG)2 moiety must hold an anti-periplanar position relative to the

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• the reaction include high functional group tolerance and excellent stereocontrol. In the same year, Zhou and co-workers reported a rhodium/bisphosphine-catalyzed asymmetric hydrogenation reaction of all-carbon aromatic rings 69 (Scheme 8) [64]. Through desymmetrization or kinetic resolution, a series

• metal catalyst to completely hydrogenate substituted naphthalene to saturated 6–6 fused bicycle (Scheme 8) [65][66]. The target decahydronaphthalene was obtained in high yield and high enantioselectivity. In 2024, Ding and co-workers reported a method for the selective hydrogenation of the carbon ring

• in quinoline to generate hexahydroquinoline using a Ru catalyst (Scheme 8) [67]. When (S,S,S)-DKP was used as a ligand, the hydrogenation of the carbon ring was highly selective. Reduction of aromatic rings via hydride or electron transfer pathways Beyond catalytic hydrogenation, aromatic rings can

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• -group elimination but through intermolecular hydride-transfer reactions as well. Therefore, the expected strategy to establish a chemical bond with a cycloheptatriene core is a reaction of a tropylium ion derivative with a nucleophile. Such reactions may involve either carbon [9][10][11] or heteroatom

• α-position, respectively. Compounds 5 represent derivatives with two substituents at the sp3-carbon atoms which sometimes tend to rearrange into the corresponding norcaradiene derivatives [29][30]. Our reactions of anion 2 with electrophiles confirm this tendency – we always observed either a

• partial positive charge on the i-positioned carbon atom [36], confirmed by an unusually downfield shifted signal of the CH fragment in the 13C NMR spectrum (δ 160.4 ppm in CD3CN) [21]. Moreover, anion 2 underwent a nucleophilic attack onto the i-position by amines to form fluorescent 5

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• vary widely across the literature, with solvents ranging from neat conditions to cyclohexane, hexanes, toluene, benzene, carbon tetrachloride, dichloromethane, and diethyl ether. Reaction temperatures span from −10 °C to 100 °C. The first detailed investigation of this transformation was reported by

• the monomer for polyvinyl chloride (PVC) [87]. The hydrochlorination of acetylene remains a key industrial process for vinyl chloride synthesis – particularly in China, where approximately 70% of the total production is based on this route. The reaction is typically catalyzed by carbon-supported

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• -nitrosocyclohexane-1-carbonitrile (1i), 2-nitro-2-nitrosopropane (1a), and 2,2-dimethyl-5-nitro-5-nitroso-1,3-dioxane (1f) were recorded on a working glassy-carbon electrode in MeCN solution (Figure 1). Tetrabutylammonium tetrafluoroborate was chosen as the supporting electrolyte. As shown by the voltammograms of

• oxidation products with full conversion of S1. The obtained data indicate that the presence of an electron-withdrawing group (NO2, CN) at the carbon atom geminal to the NO group prevents latter from facile oxidation, which, in turn, facilitate the desired nitro-NNO-azoxylation. As previously demonstrated in

• -nitrosopropane (1a) (experimental details for Table 1): In a manner analogous to one described in [87], an undivided 10 mL electrochemical cell was equipped with a platinum plate, stainless steel, nickel, graphite, carbon felt, or glassy carbon plate anode (40 × 10 mm) and a platinum plate, platinum wire (d = 1

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• functional group, the presence of which should affect their diastereomeric structure. We have found only one work describing the use of 1,3-diaminopropan-2-ol to form heterocycles, where it is reported to react with chloroacetaldehyde and carbon dioxide as an N,N-dinucleophile only, giving hexahydro[1,3

• (Figure 2 and Figure 3), the piperidone ring has a half-chair conformation in which the pseudo-equatorially located trifluoromethyl group is a conformational anchor. The five atoms of the six-membered piperidone ring are coplanar, and the trifluoromethyl-substituted carbon atom С(8) is significantly

• substituent R at the bridgehead carbon atom can occupy only an axial position with respect to both cycles. On the other hand, the CF3 group is a conformational anchor and always occupies a pseudo-equatorial position, which is why it leads to the trans-configuration of the piperidone cycle. In the cis-junction

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• of the hydroxy(tosyloxy)iodobenzene (HTIB)-mediated conversion of chalcones (α,β-unsaturated carbonyl compounds) to ditosyloxy ketones is investigated. Here, at β-carbon of the chalcone, an aryl group with a para-substituent is present. Our study focuses on investigating the effect of different

• , however, a number of studies also report the formation of a carbenium ion as an alternate pathway, typically for the oxidation of alkenes with phenyl substituents on carbon–carbon double bonds [10][11][12][29][34][35]. Here, Scheme 1 depicts the reaction investigated in the current study which is, HTIB

• HTIB leading to formation of ditosyloxy ketone may not occur at all [42]. The subsequent nucleophilic addition of −OTs on Int1 takes place on β-position specifically in a syn-manner with respect to the carbon–iodine bond. This nucleophilic syn-addition leads to the formation of an intermediate referred

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• , thioethers, disulfides, phosphonothioates, and trifluoromethyl sulfides. Additionally, due to the presence of two electrophilic sites (the sulfur atom and the carbon of the nitrile function), thiocyanates can readily undergo domino-type intramolecular cyclization reactions to form heterocycles. So, if a