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

• to replace AcOH by ethanol (Table 1, entry 10), however, the use of ethanol with piperidine was controversial. We found out that, during the reaction with benzaldehyde (1a) and rhodanine (2a), a multicomponent reaction was taking place by a substitution process, leading directly to 2-amino-5

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

• , deprotonation, and intramolecular addition to ketone. Treatment of the silacycle with MeMgCl cleaved the Si–O bond and subsequent intramolecular nucleophilic substitution of the chloride with the adjacent hydroxy group yielded TMS-epoxide 41. Protonic acid-mediated opening of the TMS-epoxide, accompanied by TES

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• . Nucleophilic substitution of the nitro group with sulfur nucleophiles, including thioacetate or disulfide anions as well as thioacetamide, yielded bis(thiophen-3-yl)disulfide and sulfide derivatives. The disulfide served as a suitable precursor for the preparation of 3-alkylthio-substituted thiophene-2,5

• functionalized thieno[3,2-b]thiophenes with potential applications in pharmaceutical and materials chemistry. Keywords: aromatic nucleophilic substitution; disulfide derivative; 3-nitrothiophene; organic disulfides; thieno[3,2-b]thiophene; thiophene ring closure; Introduction Thieno[3,2-b]thiophene (TT

• K2CO3 in DMSO to give the desired product [26]. Route III, previously elaborated in our group, utilizes the nucleophilic substitution of the Cl atom in 3-chlorothiophene-2-carboxylates by methyl thioglycolate in the presence of KOt-Bu, followed by KOt-Bu-mediated cyclization to the 3-hydroxy-TTs [27

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• and functional materials (Scheme 1a) [62][63][64][65][66]. Traditional electrophilic aromatic substitution methods for the nitration of carbazole typically result in a mixture of 1-nitro-, 2-nitro-, and 3-nitro-substituted isomers (Scheme 1b) [67]. Therefore, developing a method for the regioselective

• less hindered site. Halogenated substrates 1q and 1r (3-Cl and 3-Br substitution) delivered products 2q (37%) and 2r (31%) in moderate yield. Notably, the reaction of 1r also furnished 2a (9%), indicating competitive debromination. Finally, benzocarbazole substrate 1s afforded a mixture of regioisomers

• ). Plausible catalytic cycle. (a) Representative examples of bioactive nitrocarbazoles. (b) Traditional electrophilic aromatic substitution approach for the nitration of carbazole. (c) Present work: palladium-catalyzed directed C1-selective nitration reaction. Effect of directing groups on the nitration of the

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• substitution patterns. We began with carbohydrates, as the products are analogs of the trichloroacetimidates, which constitute the most commonly used class of glycosyl donors for glycoside synthesis [23]. Their trifluoro-analogs have, however, only been scarcely studied due to the difficulties in handling the

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

• efficiently constructed by catalytic asymmetric hydroselenation, catalytic asymmetric allyl substitution, catalytic asymmetric electrophilic selenylation/cyclization, etc. The research content of this part has already been covered by relevant reviews [15][16][17], so it is not within the scope of discussion

• formation proceeded through an SN2-type nucleophilic substitution mechanism (Scheme 1). In 2025, Li and co-workers reported a highly efficient rhodium-catalyzed enantioselective C–H selenylation reaction of 1-arylisoquinolines with diselenides, employing 3,5-(CF3)2C6H3CO₂Ag and AgSbF6 as additives [19

• phenyl-substituted benzoisoquinoline derivatives. Two plausible reaction mechanisms were proposed in the study: one involving oxidative addition of Int 4, a five-membered rhodium cyclic intermediate, followed by reductive elimination and the other proceeding via a bimolecular nucleophilic substitution

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

• converted by a series of synthetic transformations to (−)-spirochensilide A (228) with a total yield of 2.2% in 22 steps starting from acetylenic epoxide 229. 4.1 Wagner–Meerwein rearrangement The isomerization of terpenes via cleavage, addition or nucleophilic substitution reactions accompanied by a

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

• + macrocycle and promotes its translation away from the acridane toward the secondary site. However, if the rotaxane contains only one recognition site, the macrocycle remains at the unfavorable acridinium station, interacting with the 9-aryl group. Therefore, substitution at this position was employed to tune

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

• ; and subsequent conversion of the ketone in 20 to the vinyl iodide in 21 – via hydrazone formation, lithium–halogen exchange, and final nucleophilic substitution – secured the Norrish–Yang cyclization precursor 22. Following systematic optimization of reaction conditions, irradiation of 22 with 100 W

• blue LEDs at room temperature constructed a single diastereoisomer 23 in 90% yield. From 23, the ABCDE pentacyclic skeleton of phainanoids (27) was ultimately established via a Mitsunobu reaction, intramolecular nucleophilic substitution with in situ-generated aryllithium, and protecting group

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

• -surfaces and which are activated for electrophilic aromatic substitution reactions. For the synthesis of W1, we initially prepared tetramethoxybiphenyl 1 (Scheme 1) according to the literature procedure involving the Suzuki coupling between 3,4-dimethoxybromobenzene and 3,4-dimethoxyphenylboronic acid [44

• discern the effect of smaller aromatic sidewalls. The synthesis of acyclic CB[n]-type receptors follows a building block approach involving the reaction of a glycoluril bis(cyclic) ether with an activated aromatic wall by a double electrophilic aromatic substitution process [30]. Scheme 2 shows the

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• envisaged that halogenation could be combined with the Baeyer–Villiger oxidation which yields the butyrolactones by excision of C5, a reaction which is tolerant to substitution at C3 and can be carried out on a kilogram scale [30]. The present work was focussed on the development of additional halogenation

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

• one way to convert a free radical to a more stable intermediate, which can subsequently undergo coupling with another radical via an SH2 (bimolecular homolytic substitution) mechanism. Lastly, some noteworthy radical processes proceed through a radical–polar crossover pathway, in which one-electron

• diazoester 24 to furnish a Co(III)-bonded α-ester radical (α-Co(III)-ester radical) with extrusion of nitrogen was proposed by the authors. Further steps include (a) 5-exo cyclization by α-Co(III)-ester radical and (b) homolytic substitution at the carbon atom by 3-exo-tet-cyclization to generate bicyclic

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

• synthetic value of this method. In 2017, the Liu group established a precise control over cyclization sequences of 1,2-diphenylacetylenes by modulating the nitrogen-substitution patterns, enabling divergent syntheses of benzo[a]carbazole and indeno[1,2-c]quinoline derivatives (Scheme 9) [16]. When the

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• optimize the reaction conditions, with particular focus on the choice of ligand, especially for non-ortho-substituted aryl bromides as substrates. Notably, the use of bulkier phosphines, such as P(t-Bu)3 and t-BuXPhos, was found to promote the reaction regardless of the substitution pattern of the

• valuable addition to existing methodologies and open further opportunities for applications in molecular probe design, functional materials, and photoresponsive systems, where ortho-substitution is often critical. General overview of azobenzene chemistry. a) Selected examples and photoisomerization of

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

• 7c compared to 7b is likely due to the structural differences, with 7a and 7c having asymmetric substitutions (methyl for 7c, R2 = H, R3 = Me and ethyl, methyl for 7a, R2 = Me, R3 = Me), while 7b having a symmetric diethyl substitution pattern (R2 = Et, R3 = Me). The comparison of the solubility of

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

• reversible C–H activation to give the six-membered intermediate C. Substitution of the acetate ligand in C by 3 caused the generation of complex D. The six-membered ruthenacycle E was then obtained by migratory insertion of acetylene into the Ru–C bond. Finally, reductive elimination of E formed the target

• nucleophilic substitution of D afforded target indeno[1,2-c]pyrrole 40a along with eliminating I. Notably, this oxidant-free and catalyst-free approach could be potentially applied in the pharmaceutical manufacture. A Rh-promoted synthesis of pyrroles through annulation of alkynes and enamides was demonstrated

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

• protonated forms (Scheme 40). HFO can be hydrolyzed to succinic acid, however, it is a slow process in aqueous solution. In NaOH solution at pH 9–10, a complete conversion of HFO to succinic acid is rapidly achieved (Scheme 41) [126]. Substitution and condensation reactions of HFO (crude from furfural

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• 77 and subsequent deprotection produced tertiary alcohol 78. Starting from this common intermediate, on the one hand, through successive manipulations by diazotization and in situ azide substitution, AgNO3-mediated aza-Cope/Mannich [62] reaction delivered ketone 79. Subsequently, a three-step

• and in situ allylic substitution with MeOH produced [3.2.1] bridged ring product 117, which was transformed into ketone 118 via nine functional group manipulations. Finally, by employing the same reaction procedures as those utilized in the total synthesis of (−)-platensilin (23), the authors

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• ]. Given the presence of the indole moiety in indolo[1,2-c]quinazolin-6(5H)-one (1), the design of novel gramine-like analogues via aminomethyl substitution at position 12 is feasible. To evaluate the influence of the urea carbonyl group on biological activity, a modified scaffold, 6-methylindolo[1,2-c

• ]quinazoline (8) [26], was also used in which the carbonyl oxygen at position 6 is replaced by a methyl group. Substitution at position C6 will enable to investigate the influence of electronic and steric changes for target affinity, while retaining the key pharmacophoric features of the indoloquinazolinone

• substitution of the terminal chloride in 11 with various cyclic amines, including pyrrolidine, piperidine, and mono-tert-butoxycarbonyl (Boc)-protected piperazine, provided a set of aminoalkyl derivatives 12а–с (Scheme 4). This strategy enables the expansion of structural diversity within this scaffold and

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

• housane. From the equatorial DZ (eq-DZ in Scheme 3), the inverted housane can be formed through a homolytic substitution (SH2) process or can be formed via a planar DR (pl-DR in Scheme 3) radical which affords retained and inverted housane [82]. In 2020, Rollins and co-workers also investigated the

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• coupling of biaryls is designated as [30 20]. In addition to biaryls, axially chiral allenes are popular targets for asymmetric synthesis. Three examples of asymmetric reactions that form axially chiral allenes are shown in Scheme 4. For example, the enantioselective nucleophilic substitution to yield

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• favored complexation, while the phenyl substitution at C4 promoted a stable coordination-bond formation. Alternatively, (S)-130 could be furnished using Cu complex 129 in the desymmetrization step with comparable efficiency (98% yield and 91% ee), and was likewise transformed into 131 in four steps

• diol 158, the ligand with only isopropyl substitution at C4 proved effective with suitable size for the substrate–catalyst coordination. A subsequent two-step sequence enabled the sythesis of olefinic carbamate 161 from benzoate 160. Treatment of 161 with Hg(CF3CO2)2 induced mercuriocyclization

• , affording monobenzoate 169 in 97% yield with 96% ee. For 2-alkyl-substituted glycerols like triol 167, complex 168 is the most efficient catalyst as the BOX ligand with a benzyl substitution at C4 provided an appropriate size for the catalyst–substrate coordination [58]. The intermediate 169 was transformed

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

• good yield and excellent enantioselectivity (Scheme 5). Notably, two distinct oxidative aromatization methods have been developed to yield diverse heterohelicene products. For instance, using DDQ as an oxidant selectively delivered hetero[7]helicenes 19 with monoamido substitution at the peri-positions

• , while utilizing MnO2 as an oxidant selectively yielded heterohelicenes 20 with bisamido substitution at the peri-positions. In 2024, Zhou, Chen and co-workers disclosed an efficient method for the asymmetric synthesis of indolohelicenoids through a sequential enantioselective annulation, followed by an

• the 1,3-phenyl rings (see 53d) or 1,3-diamino substitution (see 53e) on the calix[4]arene scaffold were also amenable to this method, which yielded a series of structurally diverse novel quinoline-containing inherently chiral calix[4]arenes. Moreover, by using CPA 4 as the optimal catalyst, the

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

• substitution, to isopropyl, then tert-butyl, subsequent increases in lipophilicity with n-hexyl and tetradecyl resulted in decreased conversions; a trend that can be more clearly perceived in Figure 4A. The combined dodecane-free results led us to speculate that it would be better to remove solvent as a

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

• ). Shining light will bring the molecule to a generic excited state (which is different for different photoswitch classes and substitution patterns and will not be treated in detail), which can then relax back to the ground state in either of the two wells. In cases where the two absorption spectra of the

• the time within 50% of the metastable isomer is thermally converted to the stable one [3]. It depends on the photoswitch class, solvent, substitution pattern, and temperature. For some photoswitch classes, proton exchange and intramolecular hydrogen bonds are known to accelerate the thermal relaxation

• Azoheteroarenes are azoswitches of which at least one aromatic ring is a heteroarene (Figure 3). The variety of heterocycles and substitution patterns that can be used gives rise to a considerable number of variants covering all the UV and visible spectrum and with thermal Z-isomer lifetimes that span from