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

• epoxide ring and acetylation resulted in the formation of two corresponding chloro-acetate isomers. The structure of one of the chloro-acetate isomers was determined via crystallographic analysis and the other by 1D and 2D NMR spectroscopy. DFT computations confirm the regioselectivity of the methanolysis

• process, highlighting its precision and efficiency. Keywords: azides; 8-azidocyclooct-4-en-1-yl 4-nitrobenzoate; DFT; epoxycyclooctane azide; methanolysis; Introduction Organic azides are very important precursors for the preparation and synthesis of various nitrogen-containing compounds, as well as

• formation mechanisms of the products yielded from the methanolysis of isomeric epoxides 9, we performed a series of density functional theory (DFT) computations using the software Gaussian 16 [26]. For this, geometry optimizations and harmonic vibrational frequency computations for the structures considered

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

• relevant example is a calix[6]arene functionalized with three hydroxamic acid groups, where a theoretical study using density functional theory (DFT) calculations showed that the complex with the uranyl is most stabilized when only two of the three hydroxamic acid units participate in binding [78]. This

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• . The CD spectrum of 1ab showed a weak positive Cotton effect around 270 nm and a strong Cotton effect around 230 nm, and that of 1ad showed a weak negative Cotton effect around 290 nm and a strong Cotton effect around 250 nm. Each TD-DFT calculations for (R)-1ab and (R)-1ad showed good agreement in

• : 254 nm): a1), a2) chromatograms monitored at 254 nm; b1), b2) CD spectrum of the first eluates in a flow cell; c1), c2) calculated CD spectra using TD-DFT calculations at the B3LYP level using the 6-311G(2d,2p) basis set for C, H, and O atoms and the SDD basis set with the corresponding effective core

• procedures, characterization data, copies of 1H and 13C NMR spectra, and optimized geometries of DFT calculations. Supporting Information File 26: Crystallographic information file of compound 1ac. Acknowledgements We thank K. Imamura (Evaluation center of material properties, IMCE Kyushu University) for

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

• analyses, and structure and electronic properties were further investigated using density functional theory (DFT) calculations. Cytotoxicity tests were used to assess the anticancer potential of both conjugates, and it was found that both compounds showed notable activity against the test MDA-MB-231 breast

• characteristics and electronic properties of compounds 7 and 8, geometry optimisations and frequency calculations were performed using density functional theory (DFT) with the B3LYP functional and the 6-31G(d,p) basis set, as shown in Figure 3 [56][57]. The input structure of compound 7 was obtained from a single

• and 3.084 eV for compound 8 based on their experimental absorption wavelengths. Compound 7 (3.098 eV) and compound 8 (3.048 eV) DFT-calculated HOMO–LUMO energy gaps agree well with the energy values obtained through experimentation. Mulliken charge analysis (MCA) of the compounds 7 and 8 The MCA of

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• products were detected under the optimized conditions (Scheme 2). Based on our previous reports [48][56], DFT calculations, and cyclic voltammetry (CV) analyses (Figure 1), anodic single-electron transfer (SET) is expected to occur first from 3, generating the electrophilic radical cation [3]·+ as 3 (Eox

• [8]helicenes 5a and 5b, we performed DFT calculations to locate the transition states with the highest Gibbs free energies. In both cases, the transition states correspond to conformations in which the terminal rings adopt a face-to-face arrangement along the helical axis (Figure 3). The calculated

• insight into the electronic transitions, we performed time-dependent DFT (TD-DFT) calculations for all oxaza[7]helicenes 6 and oxaza[8]helicenes 5 after geometry optimization at the S1 minimum (see Supporting Information File 1 and Supporting Information File 2) [62][63]. The convergence of these

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

• restored after recalcination prior to reuse. Based on DFT calculations, the authors proposed that octanol is deprotonated and coordinated to Ce, while the amide substrate is simultaneously activated electrophilically through coordination to the Ce center (A). This dual activation enables the lattice oxygen

• transition-metal-catalyzed asymmetric C–H activation reactions as a directing group, thus necessitating an efficient method for the cleavage of 8-aminoquinoline-derived amides. The role of Me2SO4 in this transformation was elucidated through DFT calculations. Methylation of the carbonyl oxygen by Me2SO4

• bioactive compounds underwent smooth esterification with TFE to give the corresponding 2,2,2-trifluoroethyl esters 82–85 in high yields. To elucidate the reaction mechanism, cyclic voltammetry experiments, control reactions, and DFT calculations were conducted. At the anode, bromide ions are oxidized to

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

• formation of azomethine ylide from alloxan (1) and ʟ-proline (2) was previously studied using DFT calculations [43]. Based on the calculated data, it was assumed that the 1,3-dipole is formed as a result of a multistage sequence: initial generation of a zwitterionic imine intermediate from 1 and 2, followed

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• the cc-pVTZ and cc-pVQZ basis sets. Natural bond orbital (NBO) analyses [12] were also performed at the same DFT level, employing the NBO7DEL, LEWIS, and STERIC keywords to suppress electron-delocalization effects and thereby quantify the contributions of Lewis- and non-Lewis-type interactions to the

• amino acid residues and water molecules, while the ligand is delineated by a contour line to distinguish it from the binding cavity. Lowest-energy type-I, type-II, and type-III conformers of the zwitterionic form of (S)-DFMO. Color labels: H = blue, C = pink, N = orange, O = red, F = yellow. DFT

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• photophysical properties of 1, particularly its ability to exhibit RTP at room temperature. TD-DFT (time-dependent density functional theory) calculations were carried out to explore and analyze the theoretical structure and electronic properties of the compound. These calculations provided valuable insights

• Shimadzu TGA-50 analyzer. Differential scanning calorimetry (DSC) was carried out on a NETZSCH DSC-204 instrument. All calculations were carried out using Gaussian 09. Ground-state geometries were optimized by DFT at the B3LYP/6-31G(d) level. Frequency calculations at the same level confirmed that the

• optimized structures correspond to true minima (no imaginary frequencies). Vertical excitation energies were computed by TD-DFT at the B3LYP/6-31G(d) level based on the optimized geometries. Electroluminescent devices were fabricated with a conventional multilayer OLED structure using ITO-coated glass

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

• be partially responsible for its high membrane permeability. To investigate if an IMHB is indeed present in 1, we combined DFT calculations with NMR spectroscopy titrations. For a system containing an IMHB, it would be expected that replacing the proton (O–H) with a deuteron (O–D) would lead to an

• isotope effect observable as changes in the 13C NMR chemical shift [18][19]. DFT calculations were based on a truncated model (Figure 6a) containing the essential elements for intramolecular hydrogen bonding. The structure was considered both in vacuum as well as with DMSO or water as implicit solvents

• and 0.1% phosphoric acid in the ratios 35:65 and 25:75, v/v for the distribution coefficient and stability experiments, respectively. The ChemStation software (Version B.04.03, Agilent Technologies) was used for instrument control and data collection. Computational chemistry DFT calculations were

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• chiral platinum(II) complex was synthesized via Sonogashira coupling and subsequent coordination of a pincer ligand to a precursor. The complex exhibited a broad absorption band ranging from 250 to 550 nm in the UV–vis spectrum, with TD-DFT calculations indicating mixed ligand-to-ligand charge transfer

• behavior, through a combination of experimental measurements and density functional theory (DFT) calculations. The experimental UV–vis spectrum was in good agreement with the DFT calculations, revealing that the electronic transitions originate from both ligand-to-ligand charge transfer (LL’CT) and metal

• spectroscopy, as well as high-resolution mass spectrometry (HRMS). Due to its low solubility, single crystals suitable for X-ray crystallographic analysis could not be obtained. Spectroscopic analysis and DFT calculations To elucidate the electronic structure of the platinum(II) complex, UV–vis absorption

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

• theory (DFT) methods. The dyes also exhibit chemosensor properties, showing selectivity for cyanide via a Michael addition mechanism that causes the disappearance of the ICT band, and a significant color change was observed in both organic and aqueous media. In addition, the interaction mechanism between

• cyanide and the chemosensor is determined by a 1H NMR study and explained by DFT calculations. Keywords: chemosensor; DFT calculations; donor–π–acceptor–π–donor based organic dyes; indan-2-one; NLO; Introduction Over the past decades, the functional heterocyclic push–pull dyes have attracted significant

• functional theory (DFT) and time-dependent DFT (TD-DFT) calculations, which were consistent with experimental results. NLO properties of the compounds were experimentally determined using the EFISH method and calculated using theoretical methods. Additionally, the thermal decomposition temperatures, an

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• for the success of the reaction. DFT calculations suggested that in the transition state (TS1), a Cl–π interaction between the chlorine atom on the zirconocene catalyst and the aromatic ring of the substrate facilitated rapid halogen atom transfer (XAT), generating a radical at the C3 position of

• potential and stabilizing the radical pathway. The DFT calculations are shown in Scheme 13A. The activation barrier for the XAT process was calculated to be ΔG‡ = 8.0 kcal/mol, indicating that this process can proceed spontaneously around room temperature. Moreover, the transition state (TS1) suggested the

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

• end of the reaction), which is sufficient to oxidize ADN. According to the performed calculations, competitive oxidation of 1a does not occur, which is confirmed by the obtained CV-data (see Figure 1 and Figure 2). According to DFT calculations, the reaction of N-radical A with 2-nitro-2

• spectroscopy using 1,1,2,2-tetrachloroethane as an internal standard. Computational details: DFT computations were performed for 1 atm. and 298.15 K in Orca 6.1.0 package [93]. Results were visualized in Chemcraft 1.8 program. For conformationally flexible structures, generation of conformational ensembles was

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

• DFT study shows that the three-membered cyclic carbocation is not formed (Scheme 3). Therefore, to obtain β,β-ditosyloxy ketones as products from such chalcones, the possible mechanism is that, in Int3 the tosyloxy group at β-position donates electrons and the negatively charged aryl group is released

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• -NOESY and DFT calculations. The tertiary amine was masked as the hydrochloride salt with concomitant ketal deprotection, which was followed by hydrogenation to remove the benzyl protecting group to obtain (±)-4-methylenegermine hydrochloride (17·HCl) in 31 steps (LLS from commercial materials) and an

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• . However, subsequent density functional theory (DFT) calculations by the Tantillo group on rearrangements of potential biosynthetic precursors revealed that structure 10 corresponds to a transition state rather than a stable intermediate of the 1,2-alkyl migration [27]. Their study further indicated that

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• of new reactions and strategies. In this work, a PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction of N-substituted cyclobutenone provided a facile approach to the direct construction of the ABCE tetracyclic framework of Aspidosperma alkaloids. DFT calculations showed

• involves a formal 1,3-C shift. Keywords: Aspidosperma alkaloids; [2 + 2]-cycloaddition/retro-Mannich reaction; DFT study; photoinduced electron transfer; Introduction Photochemical reactions, which enable the construction of topologically complex architectures from simple building blocks, have attracted

• formation of IN1. The radical cation IN1 served as the reference point for DFT investigations. As illustrated in Figure 2a, facilitated by a favorable radical cation–π interaction [31], IN1 proceeds to the first radical addition transition state (TS1), with an energy barrier of 8.3 kcal/mol. This leads to

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• , we turned to computational studies to elucidate the driving force of this pyranoside-into-furanoside isomerisation. The DFT B3LYP-D3 approach was employed for this task with additional validation of its results at DLPNO-CCSD(T) level for the lowest energy conformers. The results demonstrate that the

• equilibrium lie outside the carbohydrate ring system. Consideration of such effects is essential to rationalize the reactivity of structurally complex and densely protected carbohydrate compounds. Keywords: benzoylated galactofuranosides; DFT; DLPNO-CCSD(T); pyranoside-into-furanoside rearrangement

• in this case, a computational study was carried out. Herein, we report the obtained results. Computational Details All the calculations were performed using the ORCA 5.0.4 software package [32]. DFT B3LYP functional with the third order Grimme’s correction (D3) [33] and def2-TZVP [34] basis set were

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• excellent conversion rates (up to 95% yield) and high enantioselectivity (up to 96% ee). Notably, isoquinoline derivatives containing polycyclic naphthalene moieties or ortho-substituted phenyl groups also demonstrated good reactivity and compatibility. DFT calculations indicated that the C–Se bond

• products demonstrated complete E-stereoselectivity (E/Z ratio >20:1). Notably, under the same reaction conditions, aliphatic selenols remained unreactive. Density functional theory (DFT) calculations revealed that the rate-determining step involves the nucleophilic attack of the selenium anion in

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• product 49 (Scheme 11, path a). When aryl or alkyl substituents were introduced on the alkyne moiety, a more stable vinylidene intermediate 50 was formed via a 6-endo-dig cyclization, ultimately leading to the generation of the bicyclo[3.3.1]nonadiene product 51 (Scheme 11, path b). DFT calculations

• cleavage to form the boronated phenanthrene framework 170. It is worth mentioning that a unique skeleton rearrangement, supported by DFT calculations, was proposed in this work, which was unprecedented in BiCl3-promoted cyclization. Conclusion This comprehensive review has systematically delineated the

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• analysis, and computational methods have been widely used. For example, the absolute configuration of chaetomugilin B [19] was determined by X-ray crystallography, while that of capsulactone (1) was established through density functional theory (DFT)-based simulations of NMR chemical shifts and electronic

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• conformers, obtained via DFT calculations, show a correlation with both the sign and intensity of the experimentally observed CD spectra. Keywords: absolute configuration; chiral amine; chiral quaternary ammonium salt; circular dichroism; DFT calculation; Introduction Determining the absolute

• of all local minima employing DFT at the B3LYP/6-31G* level of theory [47]. Four low-energy conformers of (S)-3a were identified within 10.0 kJ/mol (Figure 3). Among them, conformers A and D exhibited an M twist between the long axes of the biphenyl chromophores, whereas conformers B and C displayed

• )-3a–g and (R)-3h using MMFF. All local minimum conformers were then optimized with DFT using the B3LYP/6-31G* model [47]. The lower energy conformers with relative energies ranging from 0.0 to 10.0 kJ/mol were selected. By the Bolzmann distribution based on the energy difference of the conformers at

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• mixture of propargyl alcohol 50 (0.7 mmol), NaN3 (2.8 mmol), n-Bu4NI (0.5 mmol) and MeCN (10 mL) under electrolysis (graphite rod as anode, stainless-steel plate as cathode, 11 mA) at rt for 10 h. According to the experimental results and density functional theory (DFT) calculations, a plausible mechanism

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• 0.045. These results show agreement between the electronic nature of the transition of TD-DFT, CASSCF, and CASPT2, showing that the chosen active space can capture the photophysics of the molecules. Table 1 provides the photophysical properties for the optimized ground-state geometry. However

• couplings at each 0.5 fs timestep. Our results indicate that the retained stereochemistry of housane is generated in the ground state via thermal conversion from inverted housane/diradical. Computational Details Single reference methods We used density functional theory (DFT) to optimize the ground-state

• global minima of 1, 3, and 5. The molecular geometries were optimized using B3LYP/6-31(G) [102][103]. Time-dependent density functional theory (TD-DFT) was used to calculate the vertical excitation energies, wavelengths, and oscillator strength for the first 10 excited singlet states of 1, 3, and 5. The