3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• enantioselective molecular recognition. Different chiral backbones were used for the construction of such chiral crown ethers, especially chiral 1,2-diols such as tartaric acid [5][6][7][8], propane-1,2-diol [9][10][11][12][13], cyclohexane-1,2-diol [14], carbohydrates [15], 1,1'-binapthyl-2,2'-diol (BINOL) [16

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• the formation of a borate complex [61]. Diarylborinic acids have also been exploited for stereoselective 1,1'-glycosylations through the formation of a 1-O-monoborinate ester, resulting from the complexation of a 1,2-dihydroxyglycosyl acceptor with a diarylborinic acid derivative. Concurrent

• the orthogonally protected diol acceptor 36, proved to deliver optimal stereoselectivity and the highest yields in the reaction promoted by bistrifluoromethylated tricyclic borinic acid 40, affording β,α-1,1'-linked disaccharides 37 [63] and 39 [62], respectively, in 86% yield (Scheme 4). The nature

• of the 2N-protecting group on GlcN- and GalN-derived lactol acceptors proved crucial for the success of borinic acid-promoted glycosylation, as the 2N-Troc-protected acceptor 41 failed to participate in the reaction. In contrast, the 2N-naphthalenesulfonyl (NapSO₂)-protected glucosamine-derived

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

• development, and (ii) refining existing synthetic processes through process intensification strategies. Nitric acid (HNO3) and its binary systems with sulfuric acid (HNO3/H2SO4) remain the industry-standard nitrating systems, particularly for the nitration of aromatic substrates. Motivated by environmental

• technologies including ultrasonication, microwave irradiation, and microreaction technology into conventional nitration frameworks. Nikseresht et al. developed a novel heterogeneous heteropoly acid catalyst (PMA@MIL-53(Fe)), enabled efficient regioselective nitration of phenols under ultrasonic irradiation

• , achieving 54.98% o- and 45.01% p-nitrophenol yields within 15 minutes [10]. Umrigar et al. demonstrated a microwave-assisted nitration of monochlorobenzene (MCB) for the efficient synthesis of 2,4-dinitrochlorobenzene (2,4-DNCB), achieving reduced reaction time, minimized waste acid, and enhanced yield

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

• biomolecules in organisms. However, the R/S stereochemistry of pyruvate ketal is difficult to control through chemical methods. In this study, the acid-labile pyruvate ketal linked to the 4- and 6-positions of galactose was cautiously constructed, and the X-ray analysis of the R-configured product was

• the foundational work of Kulkarni, Codée, Boons, and other outstanding groups in their studies on zwitterionic polysaccharides [7][8][9][10][11][12]. Pyruvylation of carbohydrate diols is commonly achieved through acetal substitution in the presence of acid during chemical synthesis. In this process

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

• hypophosphorous acid are commercially available in bulk amounts, however, their usage is understudied in organic processes. While NaH2PO2 has proved to be an efficient four-electron reductant in the catalyst-free reductive amination, the influence of cation in hypophosphite salt has not been studied yet. This

• the DFT calculations (Scheme 5, Figure 2). Firstly, reductive amination of an aldehyde started from a nucleophilic addition of the amine to the carbonyl group of the aldehyde. In the presence of acid, this step could occur via acidic catalysis involving a protonation step of an amine (Step_2) or

• absence of an external hydrogen source. The alternative pathway to form a hemiaminal could not include the interaction of an acid with amine or aldehyde, nevertheless, the non-catalytic path had ΔEa = 32.1 kcal/mol (TS2→3'') which meant that hemiaminal definitely emerged faster via the amine protonation

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

• ] involving 6-aryl-2-aminopyridines 27, aldehydes, and isocyanides (Scheme 5a) [35]. By employing chiral phosphoric acid (CPA) C1 as the catalyst, this reaction worked well to afford axially chiral imidazo[1,2-a]pyridines 28 in high-to-excellent yields (up to 99%) and enantioselectivities (up to >99% ee). It

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• of a dehydroalanine derivative using silane-mediated halogen atom transfer [28]. Dual catalytic approaches that merge photocatalysis with Lewis acid [29], organo- [30], or transition metal catalysis [31] have enabled access to bond formations that are otherwise challenging to achieve. In particular

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• . Unfortunately, failure was encountered here. This can be expected because the reaction site here is a bridge quaternary center (no such example was reported in literature for this) [31][32][33]. Due to this, we then converted the ester group in 12 into a carboxylic acid group, reaching 13 in 72% yield. Finally

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

• analysis in terms of stabilization energy. In addition, an analysis of the Anisotropy of the induced current density (ACID) plot [24] calculated for 1 (Figure 3B) shows a significant diatropic ring current formally associated with the peripheral model 1b. Another diatropic contribution can be assigned to

• Equation 1. (B) Anisotropy of the current induced density (ACID) diagram of compound 1. (isosurface value: 0.035 a.u.) (C) Bond distances (in Å) for fully optimized structure of 1, computed at the ground state (S0) and at the first singlet excited state (S1, in orange). Results obtained at the B3LYP-D3BJ/6

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

• this perspective article, we shall show the relationship between transition-state aromaticity and reactivity in representative pericyclic reactions. Perspective Lewis acid-catalyzed Diels–Alder cycloadditions It is well-established that catalytic amounts of a Lewis acid (LA) can significantly

• following subchapter) but also to other processes such as aza-Michael additions or processes catalyzed by species able to establish noncovalent interactions with the reactants [52][53][54][55][56][57]. Lewis acid-catalyzed carbonyl–ene reactions Similar to the Diels–Alder cycloaddition reaction, the Alder

• , which is translated into high reaction temperatures that severely limit the scope of the process. Nevertheless, as Diels–Alder cycloadditions, Alder–ene reactions can be efficiently accelerated (i.e., having lower barriers) upon the addition of catalytic amounts of a Lewis acid [62], which again

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• -containing compounds [1][2][3]. Such reactions can be initiated by electrophilic, nucleophilic or radical reagents, photoirradiation or proceed under acid-, metal-, or photocatalytic conditions. This strategy of azirine ring expansion is applicable to the synthesis of a variety of 4‒9-membered N-heterocycles

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• of polar groups, including phosphoryl acid and amine groups [62]. After several optimizations, the following sequence was adopted to remove all Bn, Bz, and Cbz groups: 1) global hydrogenolysis of Bn and Cbz groups in 12 with Pd(OH)2/C in a mixed solvent (THF/MeOH/AcOH/H2O) and 2) saponification of

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• 060-0812, Japan 10.3762/bjoc.21.120 Abstract pH-Responsive molecular switches and motors are a class of organic molecules whose three-dimensional structure can be changed by acid–base stimuli. To date, pH-responsive molecular switches have been developed using various functional groups, but further

• triggered by protonation and deprotonation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. This class of molecules has the capacity to regulate three-dimensional structures and motions of molecules through simple acid–base stimuli. This provides a high degree of control over their

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

• precursors 4a–c were then prepared by the reaction of compounds 3a–c with N-chlorosuccinimide (NCS) in dimethylformamide (DMF). The ester group-containing chloro oxime 4d was obtained by the treatment of glycine ethyl ester hydrochloride with sodium nitrite and hydrochloric acid [25] and used thereafter as

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• Discussion We recently demonstrated that Pd-catalyzed Heck reactions could be performed in CyreneTM [26]. To extend its applicability, we first compared the typical conventional organic media, selected biomass-derived solvents (i.e., levulinic acid and γ-valerolactone-based solvents), and CyreneTM in the

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

• -dichloroethane and highlight its potential for temperature sensing applications. Density functional theory calculations were performed to support our findings and to investigate the mechanisms of azobenzene–acid interactions, aiming to guide the design of azobenzene-based temperature sensors in future research

• affect the protonation itself. In this study, we investigate the temperature dependence of azobenzene protonation with the aim of utilizing it in temperature sensing. We focus on steady-state behavior of azobenzene, 4-methoxyazobenzene, and 4,4’-dimethoxyazobenzene in solution. By tuning acid strength

• . We opted for methoxy substitution on one or both benzene rings as the simplest alkoxy substituent. The protonation of azobenzene (1), 4-methoxyazobenzene (2), and 4,4'-dimethoxyazobenzene (3) is schematized in Figure 1A. In the presence of a strong acid, these compounds form an equilibrium of neutral

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• acetylene production, was investigated. The catalyst was obtained by calcination of calcium carbide slag at 600 °C (CS600) and characterized by XRD and FTIR analysis. The transesterification reactions were carried out with primary alcohols, producing fatty acid alkyl esters in 51–99% yields, depending on

• [31][32][33][34], and cosmetic industries [16][17][35][36]. Fatty acid methyl esters (biodiesel) are of particular interest due to their current use as fuel in vehicles and promising applications [37][38][39][40][41][42][43]. The esters are demanded in large amounts according to available methods for

• was calcined at 600 °C before use and the catalyst CS600 was characterized using XRD and FTIR analysis, confirming the presence of CaO as the main phase. The primary alcohols successfully reacted in the transesterification reaction to give the corresponding fatty acid alkyl ester mixtures in yields

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• several-fold higher than that of molecular switches with a single switching unit known. The comparison is made for an AB derivative (4-(phenylazo)benzoic acid) (PABA) and a pyrazole-AB derivative (E-4-((1,3,5-trimethyl-1H-pyrazol-4-yl)diazenyl)benzoic acid) (PyABA) on a graphite surface under similar

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• process of 4,4-dichloro-2-butenoic acid derivatives and bis(pinacolato)diboron is described [10]. The transformations feature excellent chemo-, regio-, and diastereoselectivities, and the resulting products are highly functionalized. Due to this, they were considered as versatile building blocks for the

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• of azoles was pioneered by Mori [28], Schreiber [29], and Zhao [30]. However, high reaction temperatures and a large amount of base or acid dramatically decrease atom economy (the percentage of reactant atoms incorporated into the desired product) and functional-group tolerance, while the use of an

• ][44] and sulfamoyl chlorides [32] can perform the coupling under basic conditions, the need for the activation of the amine as an electrophilic agent generates additional waste. This reduces atom economy and indicates lower reaction efficiency. Acid-catalysed protocols have also been specifically

• , that still required high temperatures, but the excess of amine (2 equiv) was lowered and only a catalytic amount of acid was utilised. Similar acidic protocols were subsequently developed by Li et al. [46], in which benzoxazoles were reacted with secondary amines and amides, with higher temperature

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

• fluorescence (400–500 nm) and structured UV–vis absorption spectra. Importantly, 15b showed acid/base-switchable UV and CD spectra, suggesting potential for use in responsive optoelectronic systems. Hu’s group reported an X-shaped double [7]helicene 16 functionalized with four triazole units, which

• , enantioselective synthetic approach toward azahelicenes via a chiral phosphoric acid-catalyzed multicomponent Povarov reaction or oxidative aromatization [32]. Among the synthesized compounds, compound 19 displayed dual absorption bands at 260 and 325 nm and emission peaks at 420 and 440 nm, which red-shifted to

• approximately 500 nm upon trifluoroacetic acid treatment. Both the neutral and protonated forms of 19 exhibited mirror-image CD and CPL spectra, with high |glum| values of 1.4 × 10−3 and 1.3 × 10−3, respectively, underscoring their potential for responsive chiral optoelectronic applications. Concurrently, Liu

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

• seen from Figure 5, in the spectrum of 2 in acetonitrile a single band is observed at 500 nm. Upon addition of a very small amount of trifluoroacetic acid this band disappears and a new band at 400 nm appears, suggesting that the red-shifted band can be attributed to E−. The spontaneous deprotonation

• )quinolin-7-ol (2) Diazotization of pentafluoroaniline has been recommended to be carried out in nonaqueous media or concentrated mineral acid, otherwise the coupling product always contains a hydroxy group on the perfluorophenyl ring at the position para to the azo group. It appears that when solutions of

• . Changes in the absorption spectrum of 2 in acetonitrile upon addition of trifluoroacetic acid (TFA) and triethylamine (TEA). The addition of more TFA or TE does not cause further spectral changes. Ground (M06-2X/TZVP) and excited (CAM-B3LYP/TZVP) state potential energy surface of compound 1 in toluene

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• the synthesis of 2,3-dihydro-N-sulfonyl-1,2-thiazoles was developed based on the optimized reaction of acrylic acid thioamides containing aryl- and hetarylidene fragments with N-tosyl and N-mesyliminoiodinanes (Scheme 1D). Results and Discussion The reaction of thioamide 1a with PhINTs (2a) was chosen

• involved in the formation of a weak intermolecular hydrogen bond of the C‒H···N≡C type with distances H(3)···N(3) 2.53(3) Å, C(3)···N(3) 3.436(4) Å and angle C(3)H(3)N(3) 157(2)° (symmetry transformation [1−x, 1−y, 1−z]). Conclusion Thus, we found that thioamides of acrylic acid easily interact with

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• new natural products, pseudomonins D–G (1–4) isolated alongside other three known compounds, pseudomonine (5), pseudomonin B (6) and salicylic acid (7), were elucidated based on high-resolution mass spectrometry, 1D and 2D NMR analyses. The absolute configurations of the threonine residue in compounds

• (3 and 4) isolated alongside three known compounds, pseudomonine (5), pseudomonin B (6) and salicylic acid (7) [15] from the Pseudomonas sp. UIAU-6B strain by altering the fermentation conditions using an open system shaker at room temperature [16][17][18]. Results and Discussion The bacterial strain

• 1,2-disubstituted benzene ring system was identified by the 1H NMR spectrum showing downfield methine protons at δH 7.88 (dd, J = 8.0, 1.5 Hz, H-5), 7.37 (td, J = 8.0, 1.5 Hz, H-3) 7.01 (d, J = 8.0 Hz, H-2) and 6.92 (t, J = 8.0, H-4) that were consistent with a salicylic acid unit. This was supported

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

• hydrostatic pressure (HHP) was found to be an efficient activation method in several catalyst- and solvent-free reactions and has found application for the syntheses of heterocycles and the preparation of active pharmaceutical ingredients (APIs) via acylation and acid- and solvent-free esterification. The

• -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

• of important heterocycles, the synthesis of well-known APIs, such as acetaminophen and acetylsalicylic acid, a variety of esterification reactions and the successful scale up (up to 100 g scale) of the Paal–Knorr reaction. The use of HHP appears to provide several advantages, for example, resulting