Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• , protonation of these compounds resulted in a lowering of the HOMO energy level, leading to an increase in the HOMO–LUMO gap and, consequently, greater molecular stability. In contrast, deprotonation led to an increase in the LUMO energy level, with little influence on the HOMO energy. Notably, the neutral

• operation: −x + 2, −y + 1, −z + 1. Molecular energy as a function of the torsion angle obtained from a relaxed dihedral scan at the M06-2X/def2-TZVPP level of theory. Identification of the carbon atoms used in the theoretical study of chemical shifts. In red, easily identifiable carbon atoms in the

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• ]. The use of visible light as an energy source has significantly expanded the scope of organic molecule activation and its application in organic synthesis or medicinal chemistry [12], thereby driving the fast development of various photocatalytic transformations. Among these advances, dual catalysis

• , and advanced optical and energy materials. Review Visible-light-driven NHC/4CzIPN-catalyzed reactions Recently, Shu and co-workers developed a direct and innovative preparation of highly functionalized aryl amide derivatives 3 from aryl aldehydes 1 and substituted imines 2 under mild conditions in the

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• Yilin Liu Yuchen Yang Chen Yang Sha-Hua Huang Jian Jin Ran Hong Faculty of Chemical Engineering and Energy Technology, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, P.R. China State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• the pentacyclic series itself, minor differences in emission energy were observed as the naphthalene, quinolone, and isoquinoline subunits were varied, and compounds 31–36 with N1-triazole subunit connectivity displayed generally sharper emission signals than their C5-triazole subunit connected

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• the axle occurs in rotaxane 1, the dominant absorption of the azobenzene units ensures that most of the light energy is directed toward azobenzene photoisomerization. Additionally, their different release kinetics provide more insights: rotaxane 1 causes gradual, stepwise release beginning from the

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

• valuable strategy for synthesizing natural and unnatural products from simple building blocks [4]. Three distinct photoinitiated approaches have been established for the formation of the [2 + 2] cycloadducts: direct irradiation [5][6], energy transfer (EnT) [7], and photoinduced electron transfer (PET, or

• formation of intermediate L is challenging because its ring-strain energy (Figure 1e, 52.1 kcal/mol) is higher than that of its counterpart, i.e. the bicyclo[3.2.0]heptane motif (28.3 kcal/mol) in H [24]. Herein, we report our recent results on the development of a novel strategy for the stereoselective

• 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

• ° correspondingly, after which the starting structures were fully optimized. Quite expectedly for galactose, the gt conformer was found to have the lowest energy. Supporting Information File 1, Table S1 contains the energies obtained for the three conformers and Figure 4C provides graphical representation of the

• +60° there were produced some conformers with the energy of the furanoside substantially lower than that of the pyranoside form. The energies are provided in Supporting Information File 1, Table S2 and the graphical representation is given in Figure 4C, bars 2-a and 2-b, and Figure 4B. The Altona

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• simple building blocks [72]. The main feature of light-induced transformations is the involvement of electronically excited states that occur during photon absorption, leading to the formation of reactive intermediates causing significant changes in chemical compound reactivity. As a result, light energy

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• but not limited to methyl laurate, has found application in a variety of direct and indirect food additive applications [94]. The Hansen solubility parameter is a numerical expression that quantifies a molecule's cohesive energy density from non-polar, polar, and hydrogen-bonding interactions. It is a

• . As well-known the Hildebrand solubility parameter (HSP, δT) has been defined as a measure of the cohesive energy density of a material, thus facilitating prediction of the solubility of a solute in a solvent [96]. Methyl laurate has been found to have HSPs that are in close proximity to those that

• approximately ≈ 6.57 MPa1/2. The radius of interaction (Ro) for a typical small organic molecule, such as the nitrone, is estimated to be approximately 7.5 MPa1/2 which value is usually determined for solute molecules [97][99]. The relationship between Ra and Ro is denoted by the term relative energy difference

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• peaks appeared, indicating that photoelectron transfer occurred between iodine ions and the macrocycles [27][28], and fluorescence quenching was due to the photoinduced electron transfer (PET) effect between iodine ions and acceptors, resulting in non-radiative dissipation of excited state energy rather

• synergistic binding mechanism driven by cavity complementarity, and the energy of the PBG–iodide complex is lower than that of the WDG–iodide complex, it indicates that PBG forms a thermodynamically more stable complex with iodide ions compared to WDG. This stability difference arises from the distinct

• conformational behaviors of the two macrocycles. PBG's flexible benzene ring allows for induced-fit binding, where the macrocycle dynamically adjusts its cavity to optimize interactions with iodide, minimizing energy through conformational adaptability. WDG's rigid fluorene backbone relies on a preorganized

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• increasingly require rethinking and developing new structural designs that incorporate more efficient and advanced photoswitches to fully realize their potential. Keywords: macrocycle; photoisomerization; photoswitches; rotaxanes; shuttling; Introduction Harnessing light energy to control intra- and

• , spirobenzopyran, stilbene and stiff-stilbene (Figure 2). Systems whose photoinduced behavior primarily depends on photoredox or energy-transfer mechanisms fall outside the scope of this review. Review Rotaxanes featuring photoswitches on the axle Rotaxanes that incorporate photoswitchable units into the axle are

• . Although no shuttling or energy transfer process was observed, both rotaxanes presented good photoisomerization behavior. Remarkably, the use of cucurbit[6]uril macrocycles enhanced the photoisomerization. Later, Liu and co-workers designed a symmetric [3]rotaxane where the pH-responsive shuttling motion

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• key late-stage step in this total synthesis, the Norrish–Yang photocyclization exhibits high chemoselectivity and efficiency. It regulates selectivity through C–H bond dissociation energy and restricted bond rotation, constructing a 6/6/4 fused ring system with three contiguous quaternary carbons

• : reactive substrates exhibited λmax < 460 nm (yellow-orange), whereas unreactive ones showed λmax > 460 nm (dark red-purple). This suggests insufficient excitation energy for Norrish type-II hydrogen abstraction in the latter. Such chromophore-dependent reactivity provides critical insights for designing

• cyclization of the saturated C5–C6; c) calculated Gibbs free energy difference (ΔΔG‡) for 1,5-HAT processes of 22 and 30. Total synthesis of avarane-type meroterpenoids. Total synthesis of gracilisoid A. Divergent total synthesis of gracilisoids B–I. Mechanism of the late-stage biomimetic photooxidation

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• ], and non-conventional adsorbents [14]. Although activated carbon is widely used, its ability to capture polar compounds is limited and the regeneration process is complex and energy-intensive [15]. In work that stimulated supramolecular chemists to enter the game, Dichtel and co-workers demonstrated

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• preparation of chiral β-aminoalcohols [63]. Chiral copper(I) complexes convert imidate radicals, formed transiently through energy-transfer catalysis, to oxazolines. The transformation includes a regioselective and enantioselective HAT process. Upon blue LED irradiation, oxime imidates (derived from alcohols

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• calibration was performed using leucine enkephalin as the reference compound (m/z 556.2771), introduced at 15 µL/min. Data acquisition was performed in MSE mode with alternating low collision energy (6 eV) and ramped high-energy collision dissociation (20–40 eV). The mass range was set from 50 to 1200 Da

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

• 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

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• agents, and high-energy propellants [10][11][12][13][14][15][16][17][18]. Tetrazole is also found in several bioactive compounds [19][20][21][22][23][24], such as tasosartan, alfentanil, and cefmenoxime for the treatment of hypertension, anesthesia, and bacterial infections [4]. Among the reported

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

• –Crafts alkylation products were then converted into an intermediate tryptaldehyde that underwent intramolecular olefination to form the targeted product [34]. Glycolic acid (GA) The growing impact of fossil fuel consumption has heightened the need for advancing renewable energy technologies. One

• promising strategy for sustainable energy development involves the electrochemical oxidation of biomass-derived feedstocks. Recent work by Shen et al. demonstrates that glycolic acid (GA), also referred to as hydroxyacetic acid, can be synthesized from glycerol (GLY) using a copper single-atom

• valuable chemical used in the feed and food industry, is produced by petrochemical processes. Its synthesis from biobased lactic acid (LA) offers an access from renewable resources. However, this conversion is difficult due to the high activation energy required for the hydrogenation reaction removing the

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

• Center on Advanced Chemical Engineering and Energy Materials, China University of Petroleum (East China), 266580, Qingdao, China School of Public Security and Emergency Management, Anhui University of Science and Technology, 231131, Hefei, China 10.3762/bjoc.21.159 Abstract Azobenzene-based solar

• thermal fuels have undergone significant advancements over the past four decades, emerging as a promising technology for light-to-thermal energy conversion. While these materials exhibit considerable development potential, critical challenges remain that hinder their practical implementation. In this

• analysis, we aim to clarify the current state of azobenzene-based solar thermal fuels, while mapping strategic pathways for future technological advancements in this rapidly evolving research field. Keywords: azobenzene; energy; photoresponsive; solar thermal fuels; Introduction Solar energy occupies a

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

• is fully inverted relative to the reactant geometry. In the second cluster, the inversion is only partial, with one of the carbon atoms in the methylene bridge inverted relative to the reactant. We identified each cluster's corresponding minimum energy conical intersection (MECI), indicating at least

• ; stereoselectivity; Introduction Photochemical reactions utilize light as a sustainable energy source and are considered to be ‘green’ reactions [1][2]. Organic chromophores absorb light, accessing higher-lying excited state(s) that exhibit distinct reactivities, leading to bond breaking and formation, irreversibly

• producing energy-dense compounds [2][3]. One promising strategy to access strained compounds involves gas-evolution (e.g., CO or N2) because of the associated entropic driving force; this approach has had wide utility in photomedicine and organic synthesis. For example, photochemical decarboxylation has

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• -deficient [28], thereby lowering the energy barrier for electrophilic radical addition. Increasing the reaction temperature to 70 °C proved detrimental, yielding only trace amounts of product 14 (Table 1, entry 5). Finally, replacing Mn(OAc)3·2H2O/Cu(OAc)2·H2O with other oxidants, such as ceric ammonium

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• Road, Hong Kong, China Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, China 10.3762/bjoc.21.149 Abstract A series of nitrogen (N)-doped macrocycles was successfully synthesized through palladium-catalyzed arylation. X-ray crystallographic characterization

• , theoretical calculations were performed to evaluate the energy barriers of isomerization. As shown in Figure S3 (Supporting Information File 1), the configuration observed in the crystal structure has the lower energy by 24.0 kcal mol−1 than that of the isomeric structure with two pyrene units at the same

• side. The energy barrier was calculated to be 66.7 kcal mol−1, indicating MC3 is highly conformationally stable. The optical properties of the synthesized macrocycles were investigated in dichloromethane (Figure 3). The precursors 3a,b show intense absorptions with maxima at 425 nm and 395 nm

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• by increasing the binding affinity for the lipophilic reactants and by decreasing the energy required to desolvate acid/base amino acid catalysts [34][35]. Lipophilicity has also been found to be beneficial in condensation reactions as the removed water molecules are repelled by the hydrophobic

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• ) single bond N–N. The hydrazone pathway in protic solvents could be ruled out in cases when the energy of the s-cis-hydrazone was superior to the energy of the other two transition states. For further substituent effects on azoheteroarenes, we refer the readers to the following reports by Venkataramani

• heat storage (>300 J/g) makes these compounds suitable for molecular solar thermal energy storage (MOST) [47]. Diazocines Diazocines are bridged azobenzenes (Figure 9). The added strain renders the E-isomer metastable, favouring the more stable Z-isomer. In the planar E-azobenzene, the nπ* transition

• , giving better PSSs) and improved the half-lives without interfering too much with the absorption of the E-indigo (Figure 14). Diarylated indigos like 60g showed the presence of the Z-isomer in the dark, possibly due to the stabilisation energy given by the π–π interaction between the aryl rings (Figure

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• light of climate change and the ongoing energy crisis, there is an urgent need to reform energy and chemical production by prioritizing environmentally sustainable methods that are both practical and broadly implementable. Styrenes are industrially important bulk chemicals [39], with an estimated global