C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• temperatures between 180–240 ºC in a maximum yield of about 30–40% (Scheme 14) [72][73]. Dihydroxyacetone (DHA) The formose process is the conversion of formaldehyde to glycolaldehyde and 1,3-dihydroxy-2-propanone (dihydroxyacetone, DHA). A computational protein-directed evolution allowed to create "formolase

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• ]. Since Olmsted’s pioneering exploration of azobenzene compounds as solar thermal fuels in 1983 [42], significant breakthroughs have been achieved through interdisciplinary integration of organic synthesis, functional materials engineering, photophysical mechanism analysis, and computational chemistry. So

• transition behavior, achieving high gravimetric energy densities (300–400 J/g) with long-term storage stability (Figure 6d). Grossman and Durgun proposed methods for incorporating azobenzenes into macrocyclic structures [82]. Their computational models indicated that the molecular rings connecting the

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

• synthetic organic chemists. We report a computational study on the mechanism of diazabicyclo[2.2.1]heptenes to address long standing mechanistic questions. Indeed, the mechanism of these reactions has been disputed for over six decades. We employed non-adiabatic molecular dynamics (NAMD) simulations

• ][68][69][70][71][72][73][74][75][76][77][78] mechanisms of cyclic azoalkenes have been studied with experimental and computational techniques for more than six decades, in solution [51][55][59][60][61][64][67][69][70][73][74][75][76][78][79], gas phase [50][55][62][64][65], and solid state [60][63

• observation aligns with previous computational studies on the photodenitrogenation of DBH. The black dots represent the hopping points, the geometries where the trajectory crosses from S1 to S0. Figure 4 shows that the first σCN bond breaks on the S1 surface, while the second σCN bond breaks after relaxation

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• , however, did not reveal any significant change in the absorption profile. To gain further insight, time-dependent density functional theory (TD-DFT) calculations were carried out (for details of the computational studies, see Supporting Information File 1). In line with the UV–vis studies, comparison of

• : Experimental procedures, characterization data of all isolated products, details of UV–vis, time-course and computational studies as well as copies of NMR spectra for novel compounds. Acknowledgements We thank Prof. Dr. Beate Koksch and the AG Koksch (FU Berlin) for supervisory assistance and helpful

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• derivatizations. Based on experimental and computational studies, the origin of helical chirality in this method was elucidated. We proposed that the asymmetric Povarov reaction would generate a pair of diastereomeric tetrahydroquinoline derivatives displaying helical conformation, with a modest energetic barrier

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• development of liquid crystals, ion carriers, and other technologies dependent on precise molecular properties. Computational Details The fluorinated cyclopropanes shown in Figure 1 were optimized using density functional theory (DFT) at the B3LYP-GD3BJ/6-311++G(d,p) level [20][21][22], which includes

• dispersion corrections to improve the modeling of nonbonding interactions [23]. The same computational protocol was applied to cyclopropane, methane, and methyl fluoride, used as reference molecules in the isodesmic reactions. This methodology has proven reliable for predicting the energetics and properties

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• Abstract In this paper, the behavior of a bicolor fluorescent indicator for the detection of barium cations formed by double-beta decay of 136Xe is analyzed by means of computational tools. Both DFT and TDDFT permit to understand the origin of the bicolor fluorescent signal emitted by 1-arylbenzo[a]imidazo

• corresponding double bonds (C=C, C=N). We computed the HOMA values associated with the total, peripheral and modular patterns using the standard parameters and a more recent set based on computational parameters that take into account antiaromaticity, denoted as HOMAc [23]. According to our results, formal

• efficiency of crown ethers as components in cation-selective fluorescent probes has been extensively explored [7][30], to the best of our knowledge no previous computational DFT studies on the selectivity of crown ethers of different sizes with Ba2+ have been reported. Therefore, we explored (Scheme 2A) the

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• aromatic character in their transition states, this increased aromaticity does not necessarily correlate with lower activation barriers. State-of-the-art computational methods on reactivity, such as the combined activation strain model (ASM)–energy decomposition analysis (EDA) method, reveal that factors

• other than aromaticity govern the barrier heights of these pericyclic reactions. Keywords: activation barrier; activation strain model; aromaticity; computational chemistry; transition state; Introduction Aromaticity is arguably one of the most fundamental and extensively studied concepts in chemistry

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• S1 states of (A) (Sp)-6 and (B) (Sp)-7 (TD-MN15/6-31G(d)). Synthesis of cyclic dimer (Sp)-6 and trimer (Sp)-7. Supporting Information Supporting Information File 26: Statement of computational methods, NMR and HRMS spectra, PL decay curves, glum charts, calculated ECD spectra, and cartesian

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• : Experimental and computational details, synthesis and characterization of compounds, additional spectroscopic results, and theoretical calculations. Acknowledgements The authors acknowledge Dr. Tatsuo Nakagawa, UNISOKU Co., Ltd., for nanosecond transient absorption measurements Funding This work was supported

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• and solvent polarity, we demonstrate that the degree of protonation, and thus solution color, is highly temperature-dependent, changing from pale yellow to deep red as temperature decreases. We also present mechanistic insights and compare our experimental findings with computational results. Results

• performed to study these interactions at the molecular level. Better understanding on the protonation process emerges from combining computational findings with experimental data, as discussed in the following section. Discussion Upon protonation, azobenzene and the conjugate base of the acid form either an

• polar aprotic solvent such as DCE, we assume the formation of CIP, as supported by computational results. This discussion focuses on compound 3, which showed most promising characteristics for temperature sensing, including a larger red-shift upon protonation and a broader sensing range. DFT

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• computational quantum chemistry calculations. As seen from Table S2 in Supporting Information File 1, the deprotonation of the tautomeric proton requests substantially more energy, while the deprotonation of the phenyl OH group leads to a single E− tautomer. This fact is confirmed by a simple experiment. As

• part should be considered with care. They originate from computational quantum chemistry calculations in toluene and their aim is not to suggest definite compounds, but to show directions of structural modifications that can solve one of the problems with the switching of compounds originating from 1

• –1000 nm. The spectra were recorded with the specialized software SpectraSuite (Ocean Optics, Inc., Dunedin, USA). Computational quantum chemistry calculations: Quantum-chemical calculations in the ground state were performed using the Gaussian 16 C.01 program suite [93]. All structures (in both ground

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• -products. A computational study accompanies the experimental data to interpret the outcome of the reactions. Keywords: acetaminophen; acetylsalicylic acid; benzimidazoles; catalyst-free synthesis; cyclization; esters; high hydrostatic pressure; pyrazoles; Introduction Non-traditional activation methods

• broad agreement that a decrease in the activation volume (ΔV‡) and reaction volume (ΔV) is the driving force for these reactions [14][15][16]. A recent computational analysis of high pressure reactions by the extreme pressure polarizable continuum model (XP-PCM) improved the theoretical understanding of

• impact ionization (EI, 70 eV) mode using a 30m long DB-5 type column (J&W Scientific). Computational details To determine the reaction volume (ΔV), the volumes of the starting materials and products were calculated separately using the Gaussian 09 program suite [48]. Geometry optimizations were performed

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• epimerisation to obtain diastereoenriched spirocycles, utilising t-BuOK/t-BuOH for the anti-diastereomer 163 and LDA/PivOH at −78 °C for the syn-diastereomer 162 (dr >10:1 in both protocols). Mechanistic and computational studies suggested the following series of steps: excitation of 159 via energy transfer

• challenging amines. The combination of simple reaction conditions and excellent chemoselectivity makes this protocol very robust and suitable for both the academia and industry. Kinetic and computational experiments support an SN1 mechanism via loss of sulphur dioxide and oxetane carbocation formation. Two

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

• molecular architectures in pharmaceuticals, polymers, and agrochemicals. Despite advancements in directing group (DG) methodologies and computational approaches, predicting accurate regioselectivity in C–H activation poses significant difficulties due to the diversity and complexity of organic compounds

• . This study introduces a novel quantum mechanics-based computational workflow tailored for the regioselective prediction of C–H activation in the presence of DGs. Utilizing (semi-empirical) quantum calculations hierarchically, the workflow efficiently predicts outcomes by considering concerted

• computational cost. Validation against a comprehensive dataset reveals that the workflow achieves high accuracy, significantly surpassing traditional models in both speed and predictive capability. This development promises substantial advancements in the design of new synthetic routes, offering rapid and

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

• , indicating a smooth transition from the transition state to the product. The final dehydrative ring-opening gives products by decreasing the energy to 0.978 kJ/mol. Computational analysis indicates that the IMDA step has a high energy barrier which needs a catalyst, while the dehydrative re-aromatization

• thiophene to reduce the diene's reactivity or altering the electrophilicity of the dienophile. Based on the computational analysis of the transition states, reaction mechanisms for the IMDA and the dehydration re-aromatization process are proposed in Scheme 5. In the IMDA reaction for the preparation of

• . Conclusion In summary, we developed a reaction sequence involving GBB, N-acylation, IMDA and dehydrative re-aromatization reactions for the synthesis of imidazopyridine-fused isoquinolinones. Computational studies of the IMDA reaction indicated that the position of the R1 group on the furan ring and the R2

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

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

• computational study to design new PCs to be employed in atom transfer radical polymerization (O-ATRP) [17]. Notably, the sulfur-based structure 2 showed excellent performance for this transformation. One year later, the same research group reported its use in a reversible addition-fragmentation chain-transfer

Data accessibility in the chemical sciences: an analysis of recent practice in organic chemistry journals

• Sally Bloodworth,
• Cerys Willoughby and
• Simon J. Coles

Beilstein J. Org. Chem. 2025, 21, 864–876, doi:10.3762/bjoc.21.70

• ]. Repositories for computational materials science, such as the NOvel MAterials Discovery (NOMAD) Repository [13] and Materials Cloud [14] also enable code and workflows to be stored and shared along with the data. In the chemical sciences, sharing of thermodynamic property data is of increasing importance for

• , acquisition and processing parameters), and metadata (spectrometer specifications, acquisition and processing software, and sample information). Two of the ACS journals, J. Org. Chem. and Organometallics, give instructions for preparing data files of Cartesian coordinates from computational studies, requiring

• across the associated files, this practice concurrently discourages the use of InChI [50] and SMILES [51] identifiers. A lack of unambiguous structure identifiers makes it difficult (or impossible) to extract the associated spectroscopic data or properties for reuse through computational means. Overall

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

• , while density functional theory (DFT) calculations provided insights into their electronic properties, including reactivity and stability. This comprehensive approach, integrating synthesis, biological evaluation, and computational methods, highlights the potential of 4-(1-methylamino)ethylidene-1,5

• ± 9.93 µM). The integration of synthetic approaches, structural studies, computational analyses, and experimental validations underscores the potential of 4-(1-methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones, particularly compound 5e, as effective candidates for anti-inflammatory drug

• determine the melting points of all products. All NMR spectra were recorded on a Bruker Avance II+ 600 MHz instrument and chemical shifts (δ) are reported in ppm (parts per million) relative to tetramethylsilane (TMS) or internal deuterated solvent signals. Computational methods Prediction of drug-likeness

Carbon-rich materials: from polyaromatic molecules to fullerenes and other carbon allotropes

• Hiroko Yamada and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2025, 21, 798–799, doi:10.3762/bjoc.21.62

• chemistry, computational chemistry, physics, electrochemistry, polymer chemistry, supramolecular chemistry, and biochemistry. All are working on fascinating topics associated with these exciting molecules. Furthermore, the authors come from all over the world, not only from Switzerland and Japan but also

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• enantioselectivity achieved with the calcium catalyst remains modest, mainly due to competing pathways for the Z- and E-hydrazone isomers leading to opposite enantiomers. The experimental results confirm these computational proposals. Keywords: asymmetric synthesis; calcium–BINOL phosphate catalysis; hydrocyanation

• cyanide source. This observation complies with the results from the computational study (Figure 2). In addition, some TMSCN is consumed together with an amount of BINOL phosphate through the probably parasitic formation of catalytically inactive trimethylsilyl phosphate 3a, which we were able to

• the computational investigation, could not be isolated either – probably due to its high sensitivity to hydrolysis. However, a 2D 1H-15N NMR correlation spectrum showed no interactions of hydrogen nuclei in silicon-bound methyl groups and any of the nitrogens in the product. This led us to conclude

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• transmetalation sequence (Scheme 6). For secondary boronic esters, Morken and co-workers conducted a systematic investigation to develop an efficient activation strategy [47]. Computational studies using DFT revealed an important relationship between the length of the boron–carbon bonds and the corresponding

• , computational density functional theory calculations were performed focusing on the oxidative addition transition states (S,R)-TS8 and (S,S)-TS9 (Scheme 19b). The theoretical analysis revealed a notable energy difference between these diastereomeric transition states, with (S,R)-TS8 being 4.11 kcal/mol lower in

• with 18-crown-6. CuH-catalyzed enantioselective allylic substitution of terminal alkynes. Copper-catalyzed enantiotopic-group-selective allylic substitution of 1,1-diborylalkanes. (a) Computational and (b) experimental studies to elucidate the mechanistic details of the enantiotopic-group-selective

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• exploiting emergent geometric rules and post-assembly modifications; (3) improved screening and collection of detailed structure–activity-relationship (SAR) data for modular systems to allow systematic design, rational and computational development, and identification of novel activity. These developments

• low-symmetry conformation of cage 3 in solution [39]. Due to their stability, we can typically reclaim our cages up to quantitatively after binding or catalysis experiments, often just via a work-up and precipitation. This breadth of available data opens considerable opportunities in computational and

• , means there are opportunities in robust organic cage research not present in any other type of cavity currently explored. Automation and calculation in cavity synthesis and study The computational discovery of new materials has advanced in recent years with increased computational power [405]. Imine