Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• containing functional groups in the linker including an amine (Db1), an amide based on the V linker (Db2), and an aniline (Db3). In the case of Db1, physiological conditions would afford a protonated amine functionality that may allow for stabilization of the triplex through electrostatic interactions

• corresponding aniline with iron metal. Notably, the use of HCl as a proton source in the reduction led to significant removal of the Boc group necessitating the use of ammonium chloride as the proton source. The crude aniline was coupled to N-methylisoorotic acid 6 [37] to afford 7 in 50% yield. Surprisingly 10

• synthesis of aniline 10 and carboxylic acid 13. To access 10, the isoorotic acid derivative 6 was treated with oxalyl chloride to form the corresponding acyl chloride in situ which was then slowly added to a solution of m-phenylenediamine (9) to afford the target aniline in 62% yield (Scheme 2). Slow

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

• rely on nitroso-aniline couplings, provide a route for the synthesis of non-symmetric azobenzenes, but their substrate specificity and use of hazardous precursors limit their practical applicability [25][26][27][28]. An alternative approach involves the SEAr reaction, which utilizes potentially

• were consumed, various impurities, including biphenyls, diarylamines, aniline, and toluidine, were formed in varying amounts. Since a final dehydrogenation step is required to complete the reaction, the experiment was repeated with various oxidants tested as additives. The use of di-tert-butyl peroxide

• formed, minimizing the disproportionation side-reaction [61] becomes crucial, as this reaction produces the desired azobenzene along with equimolar amounts of aniline partners. These aniline derivatives can further participate in Pd-catalyzed cross-coupling, generating a range of diarylamines as side

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

• -metal catalyst and oxidant, was an economic and efficient protocol compared with the previous method [174][175][176][177][178][179][180][181][182][183][184]. The ruthenium-accelerated electrochemical dehydrogenative annulation of alkyne with an aniline derivative was also an efficient method to build

• the indole frame (Scheme 2) [185]. In the presence of KPF6 and NaOAc, subjection of alkyne 3 and aniline 4 to [RuCl2(p-cyneme)]2-catalyzed electrochemical annulation formed the titled indole 5 successfully. After studying the reaction in details, the best reaction conditions were acquired as following

• : a mixture of aniline 4 (0.3 mmol), alkyne 3 (0.6 mmol), [RuCl2(p-cymene)]2 (0.03 mmol), KPF6 (0.06 mmol) and NaOAc (0.06 mmol) in H2O/iPrOH (1:1, 6 mL), refluxing under electrolysis (RVC anode, Pt cathode, 10 mA) for 1.8–3.9 h. This reaction was compatible with anilines with either electron-donating

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• selectively degraded and the pure product (E)-8v could be isolated with 47% yield. On the other hand, if the amine group was too nucleophilic, as in the case of N-(4-(tert-butyldimethylsilyl)hex-5-yn-1-yl)aniline (7h), the amine N–H was arylated instead of the alkyne, resulting in the formation of N-(4-(tert

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

• synthesis of (−)-12-methoxy-Nb-methylvoachalotine (Scheme 31a) [78], (+)-12-methoxy-Na-methylvellosimine (252) was first prepared in ten steps from aniline 251, including a Larock indolization, Pictet–Spengler reaction, and Pd-catalyzed intramolecular cyclization. Tollens reaction of 252 gave diol 253

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

• electrophilic amination reaction of the aniline moiety with azodicarboxylates [37][38], the introduction of a bulky hydrazine group restricted the free flipping of the benzene ring, leading to the formation of planar chiral macrocycle 33 with high enantioselectivity (Scheme 9). Substrate scope studies

• [49] and the Liu group [50] independently reported the asymmetric synthesis of inherently chiral calix[4]arenes through an enantioselective desymmetrization strategy. Starting from the achiral aniline-containing calix[4]arenes 52, we employed the CPA 11-catalyzed asymmetric Povarov reaction [51] with

• calix[4]arenes have also been showcased. For instance, facile derivatizations of 57a afforded the inherently chiral meta-amino-substituted calix[4]arene 58 and the corresponding aniline N-oxide 59. Our study suggested that inherently chiral calix[4]arene 58 could successfully be used as a chiral

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• , the present C–H annulation reaction of aniline (1a) with styrene (2a) was initially carried out in TFE (trifluoroethanol) as solvent in the presence of 25 mol % FeCl3·6H2O as a catalyst and 1.5 equiv of TFA (trifluoroacetic acid) as an additive (Table 1, entry 1). For this reaction, 12% of 2,4

• consistently high combined yields, ranging from 92% to 95%. Probably due to steric hindrance, when the phenyl group was attached to the para-position of the aniline (1e), the corresponding products 3e along with 3e′ could be obtained in 75% yields. Electron-deficient groups at the para-position, such as -Cl

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• imidazolone derivatives and 4b–d,f,g for which we were also unable to obtain the corresponding spirocyclic products. Also, rate of the reaction for aniline derivatives 1,3 and 4d was too slow, and therefore, we were able to obtain only the corresponding derivative of thiohydantoin 7d. In case of thiophene

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

• molecular recognition responses, provides important ideas for the development of new cancer treatment strategies. In 2021, Han et al. explored the interactions WP5 and aniline tetramer (TANI) as host and guest molecules (Figure 19) [128]. The WP5⊃TANI complex is capable of self-assembling into

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

• magnet was charged with aniline (0.33 g, 3.5 mmol) and 1 N aqueous HCl (12 mL), and stirred at 0 °C for 30 min. A cold solution of sodium nitrite (0.38 g, 5.5 mmol, dissolved in 4.0 mL H2O) was added dropwise during 10 min and the resulting mixture was stirred at 0 °C for 2 h. The mixture was diluted by

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

• reaction time. Even the less reactive aniline gave nearly quantitative isolated yields in less than an hour, while the 1 bar control reaction yielded no detectable products. In addition to the excellent yields, the products were isolated without any purification, using a simple air-drying process to remove

• , salicylic acid, acetic anhydride, acetic acid, hexan-2,5-dione, aniline, hexylamine and 2-phenylethylamine) were purchased from Aldrich and used without any purification. Ethyl acetate, used to dissolve the products for GC–MS analysis (minimum purity of 99.5%) was purchased from ThermoFisher Scientific. The

• and solvent-free large-scale reaction of hexan-2,5-dione and aniline under high hydrostatic pressure To a 100 mL low-density polyethylene (LDPE) bottle was added hexan-2,5-dione (65.14 g, 0.57 mol) and 1.0 equiv aniline (59.27 g, 0.57 mol) to fill up the entire reaction vessel, then the bottle was

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• groups attached to the aniline, such as OMe, F, CF3, Me, and Br, were tolerated and did not greatly differ in terms of yield. With respect to substituents located at the alkynyl moiety, diminished yields were obtained for N,N-dimethylaminophenyl-substituted derivatives 4k and 4l and for m-tolyl

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• pyrazolodiazepines 16a–d were obtained in consistently high yields of 84–96%. Notably, the synthesis of the parent pyrazolodiazepine 16a was scaled up to 3.5 mmol without a substantial decrease in isolated yield. To explore the influence of the amine component on the process, an extensive subset of aniline-derived

• substrates 15e–l was tested. The process proceeded efficiently in all cases, yielding pyrazolodiazepines 16e–l and demonstrating tolerance for various substituents on the aniline-derived aromatic fragment, including alkyl, halogens, electron-donating alkoxy groups, as well as electron-withdrawing

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• %). Results and Discussion Synthesis The PAPs in this study were obtained in a straightforward, three-step metal-free synthesis from commercially available aniline derivatives adapting known procedures [31][38]. An overview of the compounds used in this study and their synthesis is displayed in Scheme 1

• . First, a diazotization of a given aniline 1 and reaction with 2,4-pentanedione gave intermediate 2, with yields which strongly depended on the residue in the para-position. Specifically, the residues bearing an electron-donating group (EDG) such as -OMe or -OH showed low yields because of the poor

• reactivity of the diazonium salt. When strong electron-withdrawing groups (EWGs) were introduced, the yield was also reduced, likely due to the low nucleophilicity of the aniline derivative and the ineffective formation of a diazonium salt. An annulation reaction of compound 2 was performed with either

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• not be proven. Overview of spectroscopic data of the newly synthesized compounds. The data given for the carbon analogues C-NBD1 (2-bromo-3-tosylbicyclo[2.2.1]hepta-2,5-diene) and C-NBD2 (N,N-diphenyl-4-(3-tosylbicyclo[2.2.1]hepta-2,5-dien-2-yl)aniline) were previously published [40]. Supporting

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• , and all substituted anilines afforded high yields of phosphoramidates. However, N-methyl- and N-ethylanilines showed lower yields and electron-donating groups led to a reduced yield compared to unsubstituted aniline. Further, KI performed best as the electrolyte and catalyst at 50 °C (Scheme 20). The

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• report the copper-catalyzed synthesis of tetrahydroquinoline derivatives via a domino reaction of aniline with cyclobutanone oxime. This method demonstrates a selective approach for generating bioactive tetrahydroquinoline scaffolds, which have broad applications in pharmaceutical chemistry. The reaction

• conditions were optimized for the effective formation of tetrahydroquinoline derivatives with varying substituents, showing high yields under mild conditions. Mechanistic studies suggest a catalytic cycle involving nucleophilic attack by the aniline on the cyclobutanone oxime, followed by cyclization to form

• under copper catalysis. After extensive optimization of the reaction parameters, the desired product 3aa was obtained in 92% yield under the following optimal conditions: the reaction between aniline (1a) and cyclobutanone oxime (2a) as the model system, hexane as the solvent, and copper(II

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• conversion of DMSO to MMS, a wide range of 4-arylquinolines can be synthesized (Scheme 8, path I) [24]. In this reaction, the persulfate ion generates the thionium ion (MMS), which is trapped by a nucleophilic aniline. The loss of methyl sulfide generates an imine intermediate B, which, in turn, reacts with

• first reacts with the aniline under cobalt(III) catalysis, and the resulting intermediate C then attacks the thionium ion A. Quinolines of general structure II are formed after the loss of methyl sulfide from intermediate D, followed by final cyclization of intermediate E (Scheme 8, path II

• ). Additionally, the Tiwari group developed a metal-free protocol using only K2S2O8 as an oxidant for the activation of DMSO to MMS (Scheme 8, path II) [38]. Under these conditions, an alternative mechanism arises in which the imine intermediate B, formed as previously stated through reaction between the aniline

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• formation and N-Boc-protection [24] provided nitroarene 5 in 40% yield over three steps. Reduction of the nitro group was performed with Pd/C and hydrogen to obtain aniline 6 in 98% yield, which served as a precursor for mono- and dimethylated unit B derivatives 7 and 8, respectively. While dimethylaniline

• 8 was obtained in good yield of 61% through reductive amination with excess formaldehyde and NaBH3CN as reductant, the selective installation of only one methyl group, providing monomethyl aniline 7, proved to be more troublesome. Either reductive amination using the same protocol, but under strict

• values of the primary (IC50 (CCRF-CEM) = 580 pM) and tertiary (IC50 (CCRF-CEM) = 54 pM) amine derivatives (Figure 1B) [20][35], showing a strict increase in cytotoxicity with increasing degree of aniline methylation. The same trend was also observed for unit D derivatives modified with amino groups [19

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• -workers in 2022. They reported the photo-thermo-mechanochemical approach for the synthesis of quinolines from sulfoxonium ylides and 2-vinylanilines promoted by an iron(II) phthalocyanine (FeIIPc) photocatalyst (Scheme 3) [65]. First, a mixture of 2-(1-phenylvinyl)aniline (3.1), sulfoxonium ylide 3.2, and

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• is reoxidized to Cu(I) 121 at the new anode. The Cu(I) species 121 is either oxidized to the Cu(II) complex by oxygen or plated again on the cathode. The Cu(II) catalyst reacts with aniline to produce a Cu(II) intermediate 122, which then generates a Cu(III) complex 124 through transmetalation of

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• is plausible to assume as the key step for ring formation an aza-Diels–Alder reaction between the alkyne and the imine generated by dehydration between the aldehyde and aniline. The catalyst promotes the formation of the imine XI, while the high regioselectivity is ascribable to the favored

• orientation between the electron-rich nitrogen of the diene and the electron-poor carbon of the alkyne. A different one-pot procedure affording tetrahydropyridines was developed employing two molecules of aromatic aldehydes, ethyl acetoacetate and two molecules of aniline. The copper triflate catalyst acts in

• additive. Some control experiments support a mechanism whose key intermediates are the formation of the iminium ion XIX, originated from aniline with formaldehyde which serves as the C1 building block, and the generation of the cyclic α,β-unsaturated ethers XX by Cu(OTf)2-catalyzed dehydrogenation of the

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

• organocatalyst C21 was studied in 2019 (Scheme 21) [44]. A broad range of aniline and phenol substrates was studied. The best results were accomplished with products containing a Boc-protected amino group on the aniline or 2-aminonaphthalene frame (66a–g), achieving very good yields and excellent

• (Scheme 33) [58]. Axially chiral products 106 were prepared in very high yields and exquisite enantiomeric purities. The presence of a methyl group in the aniline ring's ortho position proved to have a negative effect on the enantioselectivity, presumably due to the unfavorable steric interaction with the

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• Hz, 2H), 3.18 (m, J = 3.76 Hz, 2H), 3.87 (s, 3H), 3.88 (s, 3H), 7.10 (s, 1H), 7.16 (s, 1H); 13C NMR (151 MHz, CD3OD) δ 29.96, 40.85, 56.11, 56.26, 112.74, 113.86, 113.87, 117.99, 126.84, 153.15, 155.24; ESI-MS m/z: [M + 1]+ 249.1; found, 250.1; mp 260–261 °C. Aniline hydrochloride (7b): The product

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• -coupling to give 32 or chemoselective Negishi coupling to give 33 [74]. Finally, BPin 21 could be oxidised to the phenol derivative 34 or cross-coupled with piperidine under Chan–Lam conditions to give the aniline derivative 35 in good yield [75]. Conclusion In summary, we have developed a general method