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

• condensation-type reaction between aromatic aldehydes with rhodanine or thiazolidine-2,4-dione [39]. Various protocols have been reported employing diverse catalyst systems and reaction conditions. Common catalysts include inorganic bases such as sodium acetate (NaOAc) [40], urea/thiourea [41], NaOH [42

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• groups by sodium borohydride and then converted to chloromethyl groups by treatment with thionyl chloride, to give compound 2. The reaction of compound 2 with thiourea in THF gave compound 3 as a white solid in 96% yield. Compound 3 was characterized by 1H and 13C NMR in DMSO-d6 as a solvent (Figure 1

• synthesis of an analogous tetrakis(thiuroniumethyl)tetramethoxycalix[4]arene tetrachloride [48]. Compound 2 (100 mg, 0.077 mmol) and thiourea (1.5 equiv per chloromethyl unit) were dissolved in THF (4 mL) and the solution was refluxed for 15 h to give a white precipitate. After cooling, the solid

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

• (Scheme 4). In 2025, Yang, Lu, and co-workers employed bifunctional catalysts, including chiral thiourea derivatives or chiral phosphoric acid, to activate alkynes and selenols through multiple hydrogen-bonding interactions, thereby achieving an enantioselective hydroselenation of alkynes [22]. All

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• in high yields (Scheme 1, path c) [10]. Further expanding the scope of enantioselective approaches, a Michael/cyclization cascade reaction between 3-aminooxindoles and 2-enoylpyridines, catalyzed by a cinchonidine-based thiourea organocatalyst, was developed. Subsequent treatment with HCl in methanol

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

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• [52]. The key design features are: 1) The mannose groups at the upper rim confer specific recognition ability for cancer cell surface receptors; 2) The hydrophobic core formed by the alkyl chains at the lower rim and the hydrogen-bonding network constructed by the thiourea unit can efficiently

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• of the resulting products in developing chiral organocatalysts was investigated as well. For instance, 28a was converted to a thiourea-tertiary amine 29 through a four-step procedure in an overall 36% yield. This compound was then utilized as the catalyst in the electrophilic amination reaction

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• -containing compound [38]; the stability of these compounds is contingent on the nature of the substituents bonded to the thiocarbonyl group, which reacts with nitrile oxide [41]. It has been demonstrated [7] that 1,4,2-oxathiazoles derived from thiourea are among the least stable compounds, gradually

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• , the signal located at 162.9 ppm was attributed to the C=S unit (thiourea type) and the chemical shift corresponded in this case very well with the respective data found for the N-insertion products of the reaction of 4a with dimethyl 2-phenylcyclopropane-1,1-dicarboxylate [11]. In addition, elemental

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• most effective solvents for gold [20]. Because of the high toxicity and strong environmental impact of cyanides, eco-friendlier alternatives are currently under research. Some are based on replacing cyanide with less harmful chemicals, such as thiocyanate, thiourea, or thiosulfate. Another alternative

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• , carbohydrates, or thiourea [5][6][7][8]. Going even more back in time, we shall recognize the work of Eder, Sauer, Wiechert, Hajos, and Parrish on the proline-catalyzed Robinson annulation in the 1970s [9][10]. In light of this, organocatalysis appears to be 50 rather than 25 years old. But is even that correct

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• diastereoselectivity after 24 h of reaction (61% yield and 7:1 dr, Table 1, entry 14). By lowering the reaction temperature to 50 °C using the same catalyst (Table 1, entry 15), the yield of the reaction increased slightly to 73% in 24 hours. Disappointingly, the bifunctional thiourea THIO-1 gave a lower yield and

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• thiourea [112], keeping acetyl or benzoyl protection intact (Scheme 7) [113] which contributed to the selective deprotection of sugars in systematic oligosaccharide synthesis. The chloroacetyl group can also be similarly selectively deprotected with other reagents like N,N-pentamethylene thiourea [114][115

• with significant yield and selectivity (Figure 2). They could also be selectively cleaved with thiourea without affecting other ester-type protecting groups and implemented the antimigratory attribute of the benzoyl group coupled with the neighbouring group participation property making them a

• versatile substitute of the chloroacetyl protection for oligosaccharide synthesis. However, since the thiourea deprotection is often quite slow in nature requiring the application of heat for a prolonged period, there is always a possibility of extensive side reactions producing undesired side products

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• enantioselectivities. Compound 66d was incorporated into a thiourea organocatalyst framework and successfully tested in kinetic resolution with 73% enantioselectivity. The chiral phosphoric acid (CPA) (R)-C22 was used to catalyze the formation of a C–N chiral axis in the axially chiral product 68 from biarylamines 67

• either debenzylated and subsequently transformed into a thiourea organocatalyst or turned into an axially chiral sulfonamide. In 2022, Yang et al. presented their (3 + 2) formal cycloaddition of alkynylindoles 184 with azonaphthalenes 185 catalyzed by the SPINOL-based CPA C26 (Scheme 54) [82]. The

• thiourea organocatalyst was prepared. Hou et al. investigated a way to prepare axially chiral compounds that contain both benzimidazole and quinoline rings 189 (Scheme 55) [83]. One route to access such compounds was possible through the reaction of 2-alkynylbenzimidazoles 187 with o-aminophenylketones 188

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• their structure will be described. In 2012, Wang and co-workers reported a bifunctional thiourea-catalyzed aza-Diels–Alder reaction of cyclic keto/enolate salts 1 and N-tosyl-2-methylene-but-3-enoates 2 (Scheme 1). After a screening of the reaction conditions they found that organocatalyst I, acetic

• organocatalyst acts as a Lewis base forming an enamine which raises the HOMO energy of the dienophile, while the thiourea moiety acts as a Lewis acid, lowering the LUMO level of the diene (Scheme 1). A confined transition state is formed providing a high enantiocontrol of the reaction. In 2016, Shi and co

• -workers reported a cinchona alkaloid-derived thiourea-catalyzed regio- and stereoselective cycloaddition of 3-isothiocyanatooxindoles and imines containing two or three electron-deficient unsaturated bonds [25]. Firstly, the (3 + 2) cycloaddition of 3-isothiocyanatooxindoles 4 and aldimines 5 was explored

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• securing the enantioselectivity of the reaction by locking the catalyst in the more active and enantioselective Z-configuration (Figure 2). Further, the authors found that H-bond donors featuring urea, thiourea, and guanidine motifs were either inactive or provided racemic mixtures. Among 3,5-dichloro

• [39] developed a direct, highly enantioselective three-component reaction between aromatic acetals, BocNH2, and various 2-monosubstituted or 2,3-disubstituted allyltrimethylsilanes in the presence of 10 mol % of triethylsilyl triflate (TESOTf) and 10 mol % of the chiral bifunctional thiourea catalyst

• . In the optimisation of the catalyst 78 structure, several important observations were made (Scheme 19). Replacing thiourea (91) as the H-bond donor unit with squaramide (93) or urea (92) did not affect the enantioselectivity of the allylation of the benzaldehyde-derived acetal. On the other hand

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• product with 93% ee after 24 h, while the bifunctional primary amine-thiourea catalysts (system B) required 4 days to provide an adduct with similar enantioselectivity. Prolonged reaction time is in general the innate nature of organocatalytic reactions employing iminium activation approaches. With the

• impressive boost of the reaction rate in the ball mill was observed (3 h vs 4 days), the stereochemical outcome suffered giving the desired adduct with 59% ee instead of 94% ee in solution. Owing to the introduction of an additional functional group in the form of a thiourea moiety does not entail a

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• ][4][9] or even visible light-driven methods [25][26][27][28]. We started our study from the optimization of the reaction conditions using β-ketosulfone 1, benzaldehyde and thiourea as model reaction. According to the literature, the reaction has been shown to work best and most efficiently under

• 18). Reaction scope We then used optimized reaction conditions from Table 1, entry 16 (method A) and 12 (method B) to further explore the scope of the reaction (Scheme 2). By employing various EWG/EDG-substituted benzaldehydes and urea/thiourea/selenourea we synthesized novel Biginelli products 2a–q

• with up to 95% yield. The use of selenourea has been shown to give low yields of products (up to 33%). In fact, we have thus expanded the range of available selenium-containing DHPMs in addition to the work of other authors [33][34][35]. We also attempted to replace urea/thiourea/selenourea with N

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• spaces. The confinement of the heterogeneous version of cinchona amine and thiourea catalysts was reported, leading to improved enantioselectivity values in the Michael addition of nitromethane (5) to chalcone (6) through modification of the pore size of mesoporous silica 8 or 9 (Scheme 2) [63]. Thus

• , for cinchona thiourea, enantioselectivity not only increased with reduced pore size but even reached the level of the homogeneous catalyst when the support pore size was reduced to 6.3 nm. This resulted in obtaining the (R)-configured product 7 with 63% yield and 93% ee, as opposed to a 55% yield and

• lead to a decrease in selectivity. Connon and co-workers have attached a cinchona thiourea organocatalyst to magnetic nanoparticles 13 for the Michael addition of dimethyl malonate (10) to trans-β-nitrostyrene (11) (Scheme 3) [31]. To explore the potential impact of nanoparticles on catalyst efficiency

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• ]. Other groups have also investigated the Michael donor–acceptor reactivity of curcumins [25]. For instance, a quinine-thiourea catalyzed Michael addition of curcumins to nitroalkenes reported by Ye et al. stopped at the single Michael addition stage [35]. In the subsequent year, Yan et al. demonstrated a

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• transformation (Table 1, entries 2–5). Thiourea, which is regarded as a classic H-bond donor in carbonyl activation, also could not boost the yield (Table 1, entry 6). Fortunately, it was found that the yield of 4aa was gradually increased to 64% upon adding 3a from 2.0 to 10.0 equiv (Table 1, entries 7 and 8

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• ], Reformatsky reaction [65], azalactone synthesis [66], nitro reduction [67][68], epoxide rearrangement, thiourea guanylation, and others [69][70]. In this article, we describe a simple and direct protocol for the preparation of indanones through a classical Nazarov reaction catalyzed by bismuth(III) triflate

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• benzothiazolimine species 6 which results from Boc-deprotection and subsequent condensation of the amide product onto the benzothiazolium core. Although the other identified by-product, thiourea 7, is not derived from the limiting carboxylic acid substrate, it was found to coelute with the amide product

• benzothiazolium species would avoid the formation of thiocarbonyl difluoride, which is most likely responsible for the generation of thiourea 7. Pleasingly, under these conditions, amide 5s was formed smoothly with isolation by column chromatography providing the pure product in 71% yield (Scheme 3b). Furthermore

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• strands of TMV, inhibiting their ability to multiply and cause damage to the plant. At the same time, they also display fungicidal activities against more than fourteen types of common fungi, such as Phytophthora alternaria, based on their DNA damaging properties with the thiourea derivative, showing the

• research group explored the activity of cadmium sulfide (CdS) nanotubes as heterogeneous nanocatalysts for the electrophilic condensation between aldehydes and indoles [106]. The nanorods were obtained with a solvothermal technique, where thiourea and cadmium nitrate were mixed in ethylenediamine for 10