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

• -resolved biological imaging [6], chemical and biological sensing [7], as well as energy transfer and upconversion processes [8]. The unique characteristics of organic materials, including their solubility, ease of processing, molecular structure programmability, and the tunability of their emission color

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• -withdrawing leaving groups [49][50][54], and the transesterification of alkyl phosphates has rarely been observed [55]. A possible reaction pathway is shown in Figure 5. First, triethylamine increases the solubility of phytic acid in DMF by improving its lipophilicity and accelerates the formation of

• gives a lower yield because the phytic acid forms a syrup-like precipitate in the reaction mixture due to its poor solubility in organic solvents, thereby preventing efficient release of phosphoric acid into the reaction mixture. The plot depicted in Figure 4 shows that there is almost no induction

• -exchange resin to obtain phytic acid. Cation exchange was performed via a shaking method rather than a column method owing to the low solubility of phytate in water. The 31P NMR spectrum of the obtained phytic acid clearly shows four peaks corresponding to the non-equivalent phosphorus atoms in the phytic

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

• characterization of 25CN-NBOH and report key physicochemical properties in the solid state as well as in the solution state, namely stability, ionization, solubility, partition coefficient, and membrane permeability. We show that the hydrochloride salt is a stable and well-defined crystalline compound that is also

• respect to the physiochemical properties and handling of the compound in various research scenarios. Keywords: intramolecular hydrogen bond; membrane permeability; solubility; stability; synthesis; Introduction In recent years, classical psychedelics such as psilocybin and LSD have re-emerged as

• thermogravimetric analysis (TGA) curves did not show any significant mass loss prior to the melting point, further strengthening the conclusion that 1·HCl is not present as a hydrate or solvate upon crystallization from EtOH. Characterization of 25CN-NBOH (1) in solution 1·HCl displayed a thermodynamic solubility

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• ][8][9]. Analogous to the sulfonation of indigo to synthesize the water-soluble dye indigo carmine, compound 1 was sulfonated to increase its water solubility. Thus, the desired 6,6’-dibromo-5,5’-indigodisulfonic acid disodium salt (9) was obtained by heating 1 in a 2:1 mixture of oleum (20% free SO3

• indigo derivatives, an increasing number of sulfonic acid groups results in greater solubility of the 6,6’-dibromoindigo derivative (e.g., 10 has greater solubility in water than 9) [25]. When dissolved in aqueous solution, both 9 and 10 yield a bright blue solution. As shown in Figure 1A, salt 10

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

• 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

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• ZnCl2·etherate exhibits superior catalytic activity compared to anhydrous ZnCl2. Although counterintuitive from the standpoint of Lewis acidity, this enhanced reactivity was attributed to the significantly improved solubility of the etherate complex, which compensates for its diminished intrinsic Lewis

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• amounts of sodium hydride and n-butyllithium followed by trapping with methyl iodide afforded mostly recovered maltol (2, 75%) along with traces of desired ethylmaltol (1, Table 1, entry 1). We attributed the low conversion rate to the poor solubility of the in situ-generated sodium maltolate and instead

• less nucleophilic and sterically more hindered base lithium diisopropylamide (LDA), the yield of ethylmaltol (1) increased to 25% and maltol (2) was recovered in 17% (Table 1, entry 3). Notably, treatment of maltol (2) with LDA resulted in a deep purple solution with no apparent solubility issues. We

• explore a modified and more selective approach with milder reaction parameters. In our revised strategy, we planned to introduce a transient protecting group for the free hydroxy group, thereby avoiding the necessity of dianion formation with the aim of improving solubility and stability (Table 2). We

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

• . Additionally, some substrates proved incompatible with this reaction protocol. 2-Carboxybenzaldehyde did not result in the recovery of any solid product by simple filtration, probably due to its high solubility in water. Use of aliphatic aldehydes presented a significant challenge, as only the product 3z from

• File 1, Figure S251) in various solvents, including polar aprotic solvents (EtOAc, CH2Cl2, CHCl3, DMSO, and MeCN) and polar protic solvents (MeOH and H2O). However, the use of a non-polar solvent like hexane was not feasible due to the compounds' low solubility in this solvent. The 5-arylidene derived

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

• caused by rotaxane 2, which lacks azobenzene switches, and axle 3, which lacks the macrocycle. Attempts to study the macrocycle alone without the axle were hindered by its very low solubility in the aqueous buffer. This study highlights both the potential and the limitations of rotaxane 1 as a membrane

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

• , entry 1). However, methanol proved to be an ineffective solvent due to the rapid decomposition of NaBH4 and poor solubility of substrate 3. Most of the starting material was recovered unchanged after complete decomposing NaBH4. In contrast, when ethanol (Table 2, entry 2) or isopropanol (Table 2, entry

• solubility of the starting materials in methanol, which prevented efficient conversion. Subsequently, the substrates were introduced as THF solutions into NaOMe in methanol. Under these conditions, the cyclization did occur to form the corresponding Na salts of 3-hydroxy-TTs. Upon aqueous work-up and

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

• space is shown in Figure 8a. The distribution of these selected solvents with other organic solvents in the 3D Hansen solubility space is determined by three Hansen solubility parameters (HSPs): dispersion (δD), polarity (δP), and hydrogen bonding (δH). As is well established, information about their

• similarity in solubility properties can be obtained from the distance between solvents. The identification of problematic and non-problematic solvents is facilitated by the size and color of the specific sphere representing a particular solvent. As demonstrated by the figure, the position of methyl laurate

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

• (Figure S3) in Supporting Information File 1. WDG exhibited poor solubility, which hindered the direct acquisition of its single crystal structure for characterization. However, after Boc (tert-butyloxycarbonyl) protection, a single crystal structure (CCDC Number: 2339028) of the modified compound was

• by the two structural analogs, we added a commercially available tetrabutylammonium salt (TBAI) to the body dissolved in CDCl3 (TBAI has a good solubility in CDCl3) and studied the interaction between the receptor and iodide ion by 1H NMR titration, UV–vis absorption spectroscopy and fluorescence

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

• larger aromatic walls in the form of triphenylene walls. To ensure that the targeted hosts display low aqueous solubility required for solid state sequestrants, we exchanged the O(CH2)3SO3Na groups for OMe groups. Accordingly, we targeted the preparation of W1 and W2 (Scheme 1) which contain large π

• ) for 1 hour using a ThermoMixer™ (T = 25 °C, 800–1000 rpm). For the experiments with acridine orange (100 μM, 2.4 mL) and methylene violet (38 μM, 6.4 mL) lower concentrations were used due to solubility issues. Following incubation, the samples were centrifuged (11,000 rpm, 10 min for methylene blue

• was between 240 and 1000 μM. This experiment was not conducted with methylene violet due to solubility issues and aggregation of methylene violet at higher concentrations. Time course of removal of methylene blue and methylene violet from water using H2 and G2W1. Another critical parameter in solid

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

• ligands could enhance catalytic activity and efficiency while enabling fine control over chemo-, regio-, stereo-, and enantioselectivity of reactions. Ligands enhance both the thermal/chemical stability and solubility profiles of catalysts in specific reaction media. Thus, ligands function as a regulatory

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

• reported in Buchwald–Hartwig reactions, enhances yield by facilitating the reduction of Pd(II) to Pd(0) and improving the solubility of the base [56]. To ensure the generality of the conditions, 1-bromo-2-(trifluoromethoxy)benzene was also tested, yielding the desired azobenzene 3c in 69% yield with the

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

• physicochemical and early ADME characterization study, in the framework of which logP, pKa and logk values were calculated. Following that, kinetic solubility and in vitro gastrointestinal membrane-specific permeability measurements were carried out to assess the lead-likeness of the compounds. Subsequently, the

• results of physicochemical and early ADME characterization for hydrazones 7 and 9, and target compounds 3 and 10 are summarized in Table 2 and Table 3, respectively (individual column charts on kinetic solubility, permeability, and membrane retention measurements can be found in Supporting Information

• surface area (TPSA) values fell in a desirable range (40–90 Å2) (see the extended table on physicochemical parameters in Supporting Information File 1, Table S1). Based on their pKa values, all compounds are non-ionizable or slightly basic. Kinetic solubility was considered good above 30 µM, moderate

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• isolated and structurally characterised (using, where appropriate, HMBC, COSY and nOe NMR methods; see Figure 3). In general, the yields of these products were rather low, which may stem from poor (co-)substrate solubility in some cases; and/or competitive O–H insertion into adventitious water. On the

• tag (C17 and C18) were used. The reactions were assembled from stock solutions, with some variation in stock concentrations to improve solubility. After 24 h, the reaction products were analysed by LC–MS, and promising reactions selected for mass-directed purification. Seven additional intermolecular

• products were obtained (see Figure 3 and Table 2). The marked improvement in product yields, compared to those observed with D1–3, may reflect the change to the workflow, i.e., variation in stock concentration to improve solubility. The diversity of the obtained products was increased by the multiple

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

• . Interestingly, for the cyclization of 3b, only compound MC3 was obtained in 85% yield, which is probably attributed to larger steric hindrance deriving from bis(trifluoromethyl)phenyl groups. These macrocycles show good solubility in common solvents, and their chemical structures have been unambiguously

• existence of inherent chirality for both MC1 and MC3, chiral resolutions using chiral high-performance liquid chromatography (HPLC) were performed. Due to insufficient solubility, MC3 failed in chiral separation via preparative chiral columns. Fortunately, two enantiomers of MC1 were successfully isolated

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

• variable and rely solely on MOF modification to create a lipophilic environment in the pores. However, because solvents improve the solubility of the reactants and products, making it easier for the reagents to reach the active sites, we were concerned that performing the reaction under neat conditions

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

• solubility, this can be improved through derivatization. Water-soluble calixarene derivatives can be obtained through functional modifications, including the introduction of sulfonic acid, amine, and carboxylic acid groups [57][58][59]. These water soluble macrocycle derivatives can be used to increase the

• solubility of drugs. The modified CAs encapsulate drug molecules within the host through host–guest interactions. The interactions between the drug and the calixarene enhance the solubility of the drug [60]. Further functionalization of these CAs' upper and lower rims with diverse moieties (e.g., amides

• dual modifications [69]. These derivatives have emerged as a research hotspot due to their unique combination of water solubility, biocompatibility, and host–guest encapsulation capability [47][52][70]. The aggregation behavior of amphiphilic CAs is closely related to the size of the macrocycle, the

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

• delocalization interactions. Among the compounds shown in Figure 1, 1.2.3-c.c. is the most polar, with a calculated dipole moment of 4.17 D. Polarity is a key molecular property, as it influences solubility, lipophilicity, and various material characteristics. For example, liquid crystals used in LCD devices

• intramolecular forces in fluorinated systems but also provide a molecular framework for the design of advanced applications. Fluorinated cyclopropanes exhibit considerable potential in pharmaceuticals, where polarity influences drug solubility and activity, and in material sciences, particularly for the

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• multifunctionality stemming not only from its strong proton-donating capacity but also its unique capability to stabilize reactive intermediates through preferential solvation effects. The optimal solvent choice must balance multiple factors: substrate solubility, nitrating reagent compatibility, temperature control

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• -naphthylmethyl ether (Nap) protecting group was removed from disaccharide 10 using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in a DCM/H2O (9:1) mixture, giving a 94% yield of disaccharide acceptor 11. To enhance solubility, the trimethylsilyl (TMS) group was selectively added at the less hindered 2-O

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• synthesis of imines and enamines [36][37]. In our reducing system H3PO2 could act as an effective reductant due to its high solubility in neat conditions (Table 1, line 1) (in form of morpholinium hypophosphite). Nonetheless reductive potential of hypophosphite is pH-dependent (−1.65 V at pH 14 vs −0.5 V at

• media. Finally, the combination of H3PO2 and KH2PO2 1:1 with the ratio of H2PO2− to amine 1:2 is optimal balance between solubility of reductant, acidity of the medium and stability of the reducing system providing the highest efficiency of the interaction. Under optimized reaction conditions, the

• system is more efficient than the earlier described usage of the pure NaH2PO2: higher solubility of the potassium, rubidium and cesium salts compared to the sodium and lithium and a proper pH of the reaction medium. Acidic catalysis strongly accelerates the rate of hemiaminal and iminium ion formation

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

• generated nitrile oxide seems to be less significant. It was found that the low solubility of products containing aromatic substituents in non-polar solvents allows for their isolation by washing the crude reaction mixture with diethyl ether to remove organic impurities and then with water to eliminate

• triethylamine hydrochloride. This method has proven to be simple and effective in most cases, with the exception of compound 5g. The moderate solubility of this compound in diethyl ether led to partial precipitation from the reaction mixture. It is worth noting that chromatographic purification is also possible

• for compounds 5a–l. However, in most cases, this method is more laborious due to the similarity in the retention factor values of the initial imines 2 and the reaction products. In this way, products 5i and 5j with good solubility in diethyl ester were isolated. A comparative analysis of compounds 5a