Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• ) products and with alkylating agents 6i–n to give the N- and O-alkylated (dialkylated) products. The alkylation of compound 5 was controlled by the molar quantities of alkylating agents and base present. Thus, compound 5 was N-alkylated using equimolar quantities of the alkylating agents 6a–h to give the

• respective derivatives 7a–h. On the other hand, compound 5 was N-alkylated as well as O-alkylated using 2.0 equivalents of alkylating agents 6i–n to yield the respective derivatives 7i–n. The formation of monoalkylated derivatives is based on the fact that the NH group of the pyrazole ring in 5 is more

• susceptible to alkylation than the OH group. However, under more basic conditions and using the alkylating agent in excess can lead to a dialkylated product. It has already been established that N-alkylation takes place before O-alkylation because the nitrogen atom is a softer nucleophile as compared to the

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• frequency values (1725–1731 cm−1). This observation may be due to the position of the ester fragment relative to the heterocyclic system. The analysis of the results of X-ray diffraction analysis shows that the torsion angle C(10)–C(3)–C(16)–O(17) of methyl esters 5a and 6c is −0.8(2), and 5(2)°, and of

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• thulium nanoparticles [26] and the use of a molybdenum-centered [27] and tungsten-centered complexes have been described in the literature [28]. The work by O. S. Wenger et al. introduces a system that mimics the Z-scheme of photosynthesis, utilizing a copper(I) bis(α-diimine) complex in combination with

• 9,10-dicyanoanthracene radical anion (DCA•−) [29]. This system effectively drives photoredox-mediated reduction and C–C cross-coupling reactions under mild red-light conditions with various aryl halides, an aliphatic iodide, and O- and N-tosylated substrates (Scheme 4a). The authors discuss two

•  4d) [30]. In a continuation of this trend, a recent study by O. S. Wenger et al. further expands the frontiers of red-light photoredox catalysis with first-row transition metals by introducing Cr(0) luminophores that exhibit photophysical properties competitive with Ru(II) and Os(II) complexes [31

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• and 8, the reaction also produced hetero-Diels–Alder reaction adducts 6 and 9. For these, CH–O 1H NMR signals in the region of 4.9–5.4 ppm were characteristic. It is worth noting that the individual isolated compounds 8 and particularly 9 were unstable when stored in solution, and boiling adduct 8 or

• the signal of the CH–O group at 5.03 ppm, as well as by ethyl bromide, which indicated the predominance of isomer 4a in the mixture. For isomers 5, preferential formation of dibromide 23 and products of carbocationic rearrangements containing an ester group, the precursor of which was compound 5b

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• , demonstrated that a wide range of disulfides were synthesized efficiently when sodium sulfinates served as substrates. The isolated yields ranged from 49% to 89% for products 2a–o. In the case of sodium arylsulfinates with various substituents on the benzene ring, we observed minimal effects on the reaction

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• Information File 1. The photochromic properties of N3, N4, and I1–I4 were investigated in n-hexane. Figure 1a,b and Figure S1 in Supporting Information File 1 show the absorption spectral changes of N3, N4, and I1–I4 in n-hexane upon UV light irradiation. Compounds N3(o), N4(o), and I1(o)–I4(o) have

• absorption maxima (λmax) at 299, 307, 291, 301, 307, and 369 nm, respectively. The molar absorption coefficients at λmax of N3(o), N4(o), and I1(o)–I4(o) were determined to be 12200, 12700, 47800, 22700, 12900, and 12700 M−1 cm−1, respectively. Upon irradiation with 365 nm, a new absorption band appeared in

• confirmed that the colorless solution of N4(o) turned yellow upon irradiation with UV light and returned to the initial color upon removal of the irradiation. The photophysical properties of N3, N4, and I1–I4 are summarized in Table 1 together with the data of N1 and N2. Thermal back reactivity in n-hexane

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• . T. and H. O.), the Japan Agency for Medical Research and Development (AMED) Strategic Center of Biomedical Advanced Vaccine Research and Development for Preparedness and Response (SCARDA) Japan Initiative for World-leading Vaccine Research and Development Centers UTOPIA program (JP223fa627001: R. T

• .), JST ACT-X (JPMJAX211B: R. T.), the Naito Foundation (R. T. and H. O.), the Asahi Glass Foundation (H. O.), JST-Mirai Program Grant Number JPMJMI23G2 (K. Y.), and the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• conventionally challenging functionalizations, such as N- or O-arylations using aryl halides [29][30][31][32][33][34][35][36][37][38] or arylboronic acids [39][40][41][42], hydrofunctionalizations of unsaturated motifs [25][43][44][45][46][47][48][49][50][51][52][53][54][55][56], the oxidation of alcohols [57

• depicted in Figure 2. The reaction is initiated by formation of the five-membered copper-containing intermediate INT-5 through coordination of Cu(OAc)2 with the N-iminoquinolinium ylide species 5. This process is followed by decarboxylative N–O bond insertion into 4, yielding the N-acyl copper(III

• ) chloride reacts with boronic acids, forming the copper aryl complex INT-16, which then undergoes decarboxylative N–O bond insertion to generate the copper nitrenoid intermediate INT-17. Thereafter, nitrene insertion into the copper–carbon bond occurs, forming a new C(sp2)–N bond (INT-18). Finally, the

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• . We expect this information to be useful for the rational application of the CF2H group in drug development and molecular design. Previous quantum mechanical calculations revealed that the CF2H···O binding energy (ΔE) ranges from 1.0 kcal/mol to 5.5 kcal/mol [14][15][18][21]. In addition, as measured

• reveal the fundamental differences between the C–H bond and the O–H bond as HB donors and provide important quantitative information for applying the CF2H group as an OH group mimic. We next attempted to establish correlations of experimentally determined HB donation ability, in terms of Kd or ΔGexp

• weak inverse association was observed between ΔGexp and ΔδDMSO–CDCl3 values for neutral hydrogen bond donors (Figure 6D). This result suggests that the CF2H···O interactions are likely to be a predominant contributor to the binding between HB donating and accepting molecules but other weak

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• noncovalent interactions, particularly intermolecular π–π-stacking and C–H···O interactions. Specifically, π–π-stacking interactions were found between two guest molecules with aromatic rings arrayed in an offset fashion with a distance of 3.3 Å (Figure 3a). Interestingly, these interactions also existed

• /or π-stacking interactions, conferring the characteristic 2:2 constitutional stoichiometry onto this host–guest complex. In addition, there were eight C–H···O interactions between the hydrogen atoms of G1 and the nearby pyridinium group of H2, with distances of 2.2–3.5 Å, and two C–H···O interactions

• and G1. The brown dotted lines show the hydrogen bond distance between H2 and the positively charged region of G1 (d[C–H···O] = 2.2–3.5 Å). The red dotted lines show the hydrogen bond distance between H2 and the proton of the phenyl group of G1 (d[C–H···O] = 2.7–2.9 Å). c) Dimeric structure showing

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

• –heteroatom (C–X, where X = N, O, or halogens) bonds in organic synthesis. Copper was one of the first transition metals employed in cross-coupling to form C–C and C–X bonds [1][2]. In 1901, Ullmann reported the first cross-coupling reaction for the formation of biaryl compounds in the presence of

• stoichiometric quantities of a copper reagent [3]. This pioneering work, known as the “classical Ullmann reaction”, was extended by Ullmann and Goldberg to enable the C–N and C–O bond formation [4][5][6]. Subsequently, key developments in Cu-catalyzed cross-coupling reactions were achieved, including the

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• coupling between these components (Scheme 1b). Among aromatic fluorides, we have targeted 2-fluorobenzofurans 1 for C–F bond activation [19]. These compounds, which we prepared efficiently via 5-endo-trig cyclization of β,β-difluoro-o-hydroxystyrenes [20][21], possess a C–C double bond with an electron

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

• alkyltrifluoroborate into its corresponding alkyl radical. o-Halo-substituted aryl selenides and sulfides 13 can be achieved by a three-component coupling reaction performed with an aryne precursor, potassium halides and electrophilic chalcogen species as reactants, in the presence of Cu(OTf)2 (Scheme 10) [23]. Under

• Pd-catalyzed cross-coupling reactions, allowing the formation of C–C and C–N bonds in the o-position of the aryl chalcogen compounds. α-Aminophosphonates 14 were the result of a one-pot condensation of an aldehyde, a primary amine and phosphite P(OMe)3 with copper triflate acting as Lewis acid

• the initial formation of imine XII and enamine XIII, reacting each other in a mechanism that involved two Mannich-type reactions (Scheme 15) [32]. Activation of terminal alkynes with Cu(OTf)2 is the key step for the preparation of furoquinoxalines 22 from o-phenylenediamine and ethyl glyoxylate

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

• enantioselectivity during the nucleophilic addition, and the subsequent aromatization completes central-to-axial chirality conversion delivering products 68. Dynamic kinetic resolution of naphthylindoles 69 was performed by reaction with bulky electrophiles such as azodicarboxylates 70 or o-hydroxybenzyl alcohols 72

• %. An extensive study on the reactivity of o-naphthoquinones 117 and 122 with 2-naphthylamines, 2-naphthols (118, 120), and indoles 123 was done in 2019 (Scheme 37) [65]. Four organocatalysts ((S)-C23, C31, C32, (R)-C23) proved the most efficient, and stereoinformation was effectively transferred in all

• cases. High yields and remarkable enantiomeric purities were achieved with all prepared products (119, 121, and 124). The proposed reaction pathway indicates the asymmetric conjugated addition from 2-naphthylamine, stabilized by a donor hydrogen bond to the organocatalyst, towards the o-naphthoquinone

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• as strong oxidizing agents [1], during the last decades HIRs have been investigated as group-transfer reagents, useful in several bond-forming reactions, such as in C–C, C–N, and C–O [2][3][4][5]. The benziodoxol(on)e family, cyclic iodine(III) reagents, stands out for their thermal stability and

• Supporting Information File 1). We propose a mechanism pathway involving the retro-Michael addition of 4, releasing acrylate and hydrogen (H2). The charge of the sulfenate anion may shift between sulfur and oxygen atoms, possibly leading to an O-Michael addition (pathway B) [35]. The intermediate of these

• reactions could undergo disproportionation, a radical process resulting in the homolytic cleavage of the S–O bond [35]. The formation of disulfide 7 isolated in the experiments can be explained by combining two radical sulfur species. Furthermore, the oxygen species generated in this radical reaction may

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

• ) cycloaddition of azoalkenes with azlactones. Enantioselective [4 + 2] cyclization of α,β-unsaturated imines and azlactones. Catalytic cycle for the chiral phosphoric acid-catalyzed enantioselective [4 + 2] cyclization of α,β-unsaturated imines and azlactones. Funding S. T.-O. acknowledges a predoctoral

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• complex, which facilitates the cleavage of the N–O bond and subsequent 1,3-cyclization, ultimately leading to the formation of 2H-azirine. Therefore, the isomerization of isoxazole 1j was carried out at a higher temperature, 82 °C, but after hydrolysis of the reaction mixture, instead of the expected

• single-crystal X-ray diffraction analysis. The reaction of azetidine with diacyl chloride 2a gave a complex mixture of products, and O-methyl hydroxylamine did not react. Diacyl chloride 2a reacts with methanol and ethanol to give diesters 11a,b (Scheme 5). An experiment with isoxazole 1a and methanol on

• , into the O–H bonds of diacid 6a (Scheme 5). Apparently, in this case, the reaction proceeds through a less sterically congested transition state. Diacyl chloride 2a was also reacted with sodium azide as nucleophile at room temperature giving dicarbonyl azide 12 in 85% yield (Scheme 6). Conclusion Two

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• iodoarene difluoride 10 being generated from iodosylarene 9 (ArI=O) and HF, with iodosylarene itself generated by aryl iodide and m-CPBA. Ligand exchange of iodoarene difluoride with nitrogen and reaction with the alkene forms aziridinium intermediate A which, after nucleophilic attack by fluoride, forms

• (Scheme 10). The selectivity of the reaction was also found to be influenced by the presence of electrolytes like TBABF4, and the ligand attached to I(III). Carboxyfluorination was observed, in which a ligand from the iodane, e.g., OAc, OPiv or o-I-OBz, adds and was found to compete with fluoroamination

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• adopts a 1,3-alternate conformation and binds simultaneously to the epoxide O-atom and iodide anion via (NH···O and NH···I) hydrogen-bonding interactions. The TBA countercation is bound to the O-atom of the epoxide ring with hydrogen bonds and is situated away from the I− anion. This crucial transition

• zero due to too strong association of trifluoroacetate with protonated porphyrin. DFT calculations suggested that the O–O bond in O2 becomes polarized upon binding in {(H4TPP2+)·(TB−)·O2}, which facilitates

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• catalyst tolerated all p-, m-, o-Cl-substituted benzaldehydes in terms of both reactivity and selectivity, affording the essentially same results as benzaldehyde (2b–d). Other electron-deficient substituents CF3 (2e) and Br (2f) did not adversely affect the reaction. However, electron-donating substituents

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• (overall) and for the top four most common phyla (Actinobacteria (A), Proteobacteria (P), Cyanobacteria (C), Firmicutes (F), and others (O)). d) and e) are the most oversampled and underexplored groups of NRP BBs, respectively. Syn-BNPs were synthesized in accordance to predicted NRP structures; shown

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• Oleg V. Bityukov Pavel Yu. Serdyuchenko Andrey S. Kirillov Gennady I. Nikishin Vera A. Vil' Alexander O. Terent'ev N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation 10.3762/bjoc.20.249 Abstract Organic peroxides have

• peroxides, oxaziridines, and their derived species are often applied as terminal oxidants [7][8]. The weakness of the O–O bond allows alkoxy radicals to form through homolysis or reduction [9]. The generated alkoxy radicals provide an accessible tool for selective radical cascades, where a variety of

• involving radical intermediates from hydroperoxides under redox conditions (Scheme 3). The reactivity of O-centered radicals is less predictable and more diverse depending on radical structure and substrate pattern than the chemistry of C-centered radicals [29][30]. Generally, peroxy radicals have a

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• carboxylic acids [10]. It was therefore obvious to use a perfluoroalkyl chain as a tether. However, a perfluoroalkyl chain as a substituent on the porphyrin has an electron-withdrawing effect and thus a negative influence on the oxidation potential. We have therefore inserted an O–CH2 group between the

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• charge on this substituent in the hypervalent bond. The long I–X distances (a = 2.758–4.165 Å) are indicative of ionic compounds, with the exception of the cyclic benziodoxolone 2, in which a covalent I–O bond is observed (a = 2.484 Å). We were unable to obtain a crystal structure of the ortho-nitro

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• copper catalyst afforded nearly better results for the arylated products. In 2022, Linde et al., demonstrated a conventional approach for achieving arylations of nitrogen- and oxygen nucleophiles via SNAr reaction, using o-fluorinated diaryliodonium salts 40, which enabled access to a greater range of

• accepting a wide variety of protective and functional groups, the method creates products with an iodine substituent that is easily accessible for product derivatization. Moreover, it is a convenient methodology for both N-arylation and O-arylation. The arylation of amines 38 was achieved in acetonitrile as

• conditions, the arylation of tyrosine methyl ester was also performed. The resulting compound was arylated at both O- and N-positions. The investigations were continued with the unsymmetric anisyl salts, and the results showed high chemoselectivity for N-arylation. Iodonium salts containing the anisyl