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

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• from esters of functionalised arylacetic acid 5 or 6 and involves two separate protocols: first, a metallacarbene, which undergoes the insertion, is generated from the corresponding diazo precursor formed either in flow via hydrazone oxidation (PS-TsNIK packed column), or in batch mode via diazo

• chlorides (Scheme 11a) [44]. The authors found that the secondary alcohol precursors were less reactive and that best results were obtained at low temperature (≤−50 °C) and in chlorinated solvents. The synthesis of these cages was later revisited by Le Drian et al. in 2011 who studied a Lewis acid-catalysed

• epoxide-opening cyclisation for the oxetane formation (Scheme 11b) [45]. The highest yield was obtained for the PhSH/I2 10:1 activator under unusually mild conditions – the authors believed it is due to the oxa-bridge which facilitates the Lewis acid coordination. In 2001, Rousseau and colleagues reported

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• in 1,2-dichloroethane giving PAHs 134–137 in high yields (71–85%). All the new PAHs exhibit characteristics typical for “true” π-extended azulenes, such as azulene-like optical absorption and narrow HOMO–LUMO gaps. In addition, compounds 134–137 show reversible stimuli-responsiveness against the acid

• , new OFET-based acid vapor sensors were developed from 150 by synergistically utilizing its charge transport and protonation−deprotonation properties. The solution-phase synthesis of a non-benzenoid nanoribbon from an azulene-containing polymer via alkyne benzannulation was reported by Morin and co

• -workers (Scheme 20) [98]. The starting polymer 152 was synthesized using Suzuki cross coupling and is regiorandom, meaning the orientation of the azulene units within the main chain is not defined. Polymer 152 was annulated using MsOH (methanesulfonic acid) yielding the non-alternant graphene nanoribbon

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• activated alkenes involving benzylic C(sp3)–H bonds through a cascade cyclization process (Scheme 1) [2]. This organomediated approach can be facilitated by a catalytic amount of Lewis acid. Using DTBP as the oxidant and IrCl3 as the promoter, a range of benzylic C–H bonds in arylmethanes

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• presumed byproducts in the addition–elimination sequence in the presence of an excess of ethanol as a cosolvent are the ethyl ester formed by Einhorn acylation [7] of the acid chloride under the standard conditions and deep colored polar byproducts (according to TLC detection) that arise from self

• -condensation of 2-methylbenzothiazolium salts 7 and intermediary formed S,N-ketene acetals 4 at elevated temperatures. Einhorn acylation is governed by the electrophilicity of the acid chloride or acylammonium species and the nucleophilicity of any nucleophilic species present in the reaction mixture. In

• dichloromethane; N = 17.10 in acetonitrile) [14] than ethanol or the S,N-ketene acetal intermediate 4. Hence, mechanistically the acid chloride first transforms to an acylammonium species as in Einhorn acylations [7]. As a consequence, for avoiding any competing ethyl ester formation, ethanol has to be omitted

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• effective generation of phosphorous radicals. Under a pure O2 atmosphere, the interception of formed P-centered radicals by excess oxygen can presumably inhibit the target process by the formation of unreactive phosphoric acid from the corresponding H-phosphonate [73][74]. The formation of phosphoric acid

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• followed by acid-mediated condensation. The linear copolymers show good solubility and carbon dioxide adsorption. Keywords: alternating copolymer; building block; formylation; gas adsorption; propellane; Introduction Combination of sp2- and sp3-hybridized atoms in core π-skeletons [1][2][3] is a key to

• -fused propellanes simply by reduction into the corresponding alcohols followed by acid-mediated Friedel–Crafts-type reactions (Figure 2a and Figure S201 in Supporting Information File 1) [67][68]. Reduction by NaBH4 proceeded well for both monoaldehydes [4.3.3]_CHO and [3.3.3]_CHO resulting in over 90

• % yield. Alcohol products, [4.3.3]_CH2OH and [3.3.3]_CH2OH, were then tested in acidic conditions using anhydrous FeCl3 as a Lewis acid. After the reactions, the alcohol proton signals at 1.54–1.58 ppm disappeared in the 1H NMR spectra, and aliphatic carbon ones at 63.1–63.2 ppm were largely up-field

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• and carboxylic acid. The palladacycle intermediate can undergo further (coupling) reactions and form a variety of products via reductive elimination. In previous studies, the rate- and regioselectivity-controlling step was identified as the formation of the palladacycle [5][6][7]. The regioselectivity

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• initial GBB reaction of aminopyridines 1 (0.5 mmol), isocyanides 3 (1.2 equiv), and furfuraldehydes 2 (1.2 equiv) was conducted in 3:1 CH2Cl2/MeOH (4 mL) using Yb(OTf)3 (0.08 equiv) as a Lewis acid catalyst under microwave irradiation at 100 °C for 1 h (Scheme 2). Nineteen distinct adducts 4 were obtained

• tested, AlCl₃ gave the best result, while CuCl, ZnCl2, PdCl2 and Sc(OTf)3 showed moderate conversions (30–55%), and InCl3 had the lowest efficiency. Without any Lewis acid we observed no conversion by LC–MS (Table 1, entry 16). During the reaction, IMDA adduct 7a was detected by LC–MS (Figure S1

• GBB reactions for the preparation of imidazo[1,2-a]pyridines 4 were conducted using aminopyridines 1 (0.5 mmol), isocyanides 3 (0.6 mmol, 1.2 equiv), and furfuraldehyde 2 (0.6 mmol, 1.2 equiv) in 3:1 DCM/MeOH (4 mL) with Yb(OTf)3 (0.04 mmol, 0.08 equiv) as a Lewis acid catalyst under microwave