Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• of 74% for bromine 2 and 78% for iodo starting material 3 (Table 3) [24]. To overcome the problems of poor yields in the arylation of N-acetyl diazocines via Stille coupling we used Suzuki–Miyaura reactions of the diazocines 2 and 3 with different arylboronic acids [25][26]. There are several

• 1. If electron-withdrawing substituents are added in ortho-position of the additional phenyl ring (12 and 13) the half-life is not affected significantly as well. An increase of about 10% of the half-lives has been observed for the weak +M substituents bromine (10) and fluorine (11) or methyl groups

• the switching behavior while weak +M substituents like bromine and fluorine as well as electron-poor heteroaromatic systems lead to increased thermal half-lives. An amino-substituted derivative 21 was obtained via Buchwald–Hartwig coupling with Boc-carbamate and subsequent deprotection. Amino

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• ; electrochemistry; hypervalent bromine; Introduction Chemistry of hypervalent bromine(III) species has experienced rapid advancements during the recent years [1][2]. The remarkable nucleofugality of aryl bromides in hypervalent bromine(III) compounds has been exploited in the generation of arynes from cyclic

• molecular nitrogen in diazonium compounds. Accordingly, pre-formed [12] or in situ-generated 2,2’-bromodiazonium salts 2 [11][13][14] furnish cyclic bromine(III) species 1 under thermal decomposition conditions (Scheme 1, reaction 1). The diazonium intermediates 2 are obtained by diazotation of 2'-bromo

• an electrochemical synthesis of cyclic diaryl λ3-bromanes under anodic oxidation conditions. Results and Discussion Symmetric 2,2'-dibromo-1,1'-biphenyl 4a possessing ethoxycarbonyl groups ortho to the bromine was chosen as a model compound for our study. We anticipated that the presence of the ester

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

• potent. Interestingly, the presence of a halogen, preferably a bromine substituent at the para-position of the acetamide group increased the antibiotic potential against S. aureus. A comparative analysis of the antimicrobial data between mono/dialkylated derivatives revealed that O-alkylation did not

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

• derivatives 8 and 9. Interaction of 4a/4b and 5a/5b mixtures with bromine. Interaction of diketone 1 with formaldehyde under various conditions. Supporting Information Supporting Information File 112: 1H and 13C NMR spectra of synthesized compounds. Funding This research was financially supported by the

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• good tolerance for both electron-withdrawing groups such as fluorine (–F), bromine (–Br), and chlorine (–Cl), as well as electron-donating substituents like methoxy (–OMe) and methyl (–Me), yielding the corresponding 6-membered tricyclic imidazoles in moderate to good yields (3b–h). Benzene rings

• example, substrates with a bromine atom occupying the 4-position and a methoxy group at the 7-position could be successfully converted into the target products (3s and 3t). In addition, doubly substituted benzimidazoles (3u–w), as well as the single imidazole (3x), were also found to be applicable. This

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

• bromine radical attack that leads to the formation of a cationic brominated copper complex 77. Anodic oxidation and subsequent proton transfer provide the desired product 73 and regenerate the copper catalyst. Olefin addition Hydrofunctionalization and difunctionalization of alkenes are valuable methods

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

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• ring with the -OMe group on 25, while the halogen (bromine) is on the opposite ring with the -OMe group on naphthalene 30. This small yet important difference allowed us to synthesize benzo[j]fluoranthenes 23 and 28 selectively with free -OH groups at different positions. Bromonaphthalene 30 was

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• , colorless, amorphous solid. ESIMS analysis of compound 1 revealed pseudomolecular ion peaks at m/z 805, 807, 809, 811, and 813 (1:4:6:4:1 [M + Na]+), which is indicative of the presence of four bromine atoms. The molecular formula of compound 1, determined by HRESIMS, was identified as C24H26Br4N4O6. The

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• brown gum. The LRESIMS of 4 indicated the presence of two bromine atoms due to a 1:2:1 ion cluster at m/z 459/461/463 [M + H]+, whilst the HRESIMS data allowed a molecular formula of C17H20Br2N2O3 to be assigned. The 1H NMR (Table 1) and edited HSQC spectra of 4 in DMSO-d6 indicated the presence of one

• due to the N-(3-aminopropyl)-2-pyrrolidone moiety, which is rarely found in natural products with <30 metabolites reported to date. The TFA salt of ianthelliformisamine E (5) was obtained as a stable brown gum. The LRESIMS of 5 indicated the presence of two bromine atoms, displaying a 1:2:1 ion

• C17H22Br2N2O4. Ianthelliformisamine F (6) was isolated as a stable brown gum. The LRESIMS of 6 indicated the presence of two bromine atoms due to a 1:2:1 ion cluster at m/z 334/336/338 [M + H]+, whilst the HRESIMS data enabled a molecular formula of C10H9Br2NO2 to be assigned. Comparison of the 1D NMR data of 6

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

• functional groups and avoids the use of highly toxic and corrosive bromine. Approaches using this approach are outlined below. Nitrogen nucleophiles In 2007, aminobromocyclisation of homoallylic sulfonamides 53 was reported by Fan, Wang and co-workers (Scheme 29) [50]. Using PhI(OAc)2 as an oxidant with KBr

• as the bromine source and Bu4NBr as a reaction promoter, racemic brominated pyrrolidines 54 were synthesised from a range of homoallylic sulfonamides 53 in excellent yields under mild conditions at room temperature. A mechanism was suggested by the authors (Scheme 29), whereby ligand exchange on PhI

• (OAc)2 with a bromide ion forms unstable PhIOAcBr. Elimination of bromoacetate then gives a reactive electrophilic bromine source, which forms a bromonium intermediate A after reaction with the alkene. Intramolecular nucleophilic attack from nitrogen forms the product 54. Chiba and co-worker reported

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

• -Butoxy and tert-butylperoxy radicals are generated through the redox reaction of bromine. Vanadium(IV) oxychloride (VOCl2) was found to be an efficient catalyst to achieve peroxidation–carbonylation of styrenes 152 with TBHP and aldehydes 153 to give β-peroxy ketones 154 (Scheme 48) [112]. V(IV)OCl2 is

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• illustrates that coupling phenyl, thiophene or other aryl moieties at this position would be extremely difficult. Furthermore, the distance between the o-bromine atoms and the nearest carbon neighbor of the β-ethyl groups is 3.7 Å, further complicates the success of coupling at this position. As discussed

• previously, enrichment to the αβαβ, isomer may be necessary to remove the impact of opposing bromine atoms on the coupling reaction. Separation of the four individual atropisomers (αβαβ, α2β2, α3β, α4) has been accomplished before in dodecasubstituted porphyrins through Ni(II) metalation [15]. The core

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• (R)-16 (Scheme 5). When the substituent R is an aromatic ring substituted by a halogen such as chlorine and bromine atoms, the amides (S)-23 were obtained in 22–27% yield and with very high optical purity ((S)-23b, (S)-23c), although as for (S)-23a, a satisfactory result (92% ee) could be obtained

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorovinyl ethers, which contains a reactive bromine atom, to afford a series of fluoroalkenes and fluoroenynes in moderate to high yields. Keywords: fluoroalkenes; fluoroenynes; multihalogenated vinyl ethers; Suzuki–Miyaura cross-coupling reactions; Sonogashira cross-coupling reactions; Introduction

• -chloro-1,1,1-trifluoroethane (halothane) in good yields (Scheme 1D) [42]. Compound 1 has a unique structure possessing three types of halogen atoms, namely bromine, chlorine, and fluorine, and it would be expected to afford multisubstituted fluoroalkenes by installing various substituents to bromine or

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• depending on the incorporated halogen on the pyran core at C4: −208.33 ppm for 12 (fluorine), −197.95 ppm for 13 (chlorine), −192.80 ppm for 14 (bromine), and −184.56 ppm for 15 (iodine). Similarly, the increase in chemical shift of F2 is smaller as exemplified with an upfield shift of −205.46 ppm for 12 to

• exception being bromine). Dipole moments for the 4C1 structures are 2 Debye larger than for 1C4 structures, making them substantially more stable in chloroform. Both chair structures have multiple C–F bonds in gauche arrangements which are stable due to hyperconjugation: there is donation from C–H bonding

• , 17, and α-ᴅ-talose 18. ORTEP diagram showing 50% thermal ellipsoid probability (except for 18): carbon (gray), oxygen (red), fluorine (green), chlorine (orange), bromine (dark red), iodine (purple), and hydrogen (white). Packing arrangement of compound compound 15; a) View down the b axis; b

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• ). Halogen bonding dimer found in the crystal structure of 7Br. Ellipsoids are shown at 50% probability (carbon: grey, nitrogen: blue, oxygen: red, bromine: orange, iodine: purple) and hydrogen atoms are shown in standard ball-and-stick model (white). Halogen and hydrogen bonding is indicated dashed. 1H NMR

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• -Addition of molecular bromine to phenyl isocyanide was reported by E. Kühle et al. to afford the corresponding 1,1-adduct (PhN=CBr2) [23]. Since dichloro compounds (RN=CCl2) [24] are the imino derivatives of highly toxic phosgene (O=CCl2), reactions using them as key intermediates are not safe synthetic

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• generated hydrazones were cyclized with simple ketones to pyrazolines. The oxidation to the corresponding 4-halo-substituted pyrazoles 69 can be achieved in a one-pot fashion by halogenation with iodine chloride or elemental bromine (Scheme 24) [102]. When cyclic ketones are used, fused products 70 are

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• -difluoroethylene and the disappearance of vinyl protons resonances in the 1H NMR spectra [78]. Addition to the C=C bond Halogen addition: 1,2-Difluoroethylene was reported to react with chlorine [46][79] and bromine [51] under irradiation, yielding 1,2-difluoro-1,2-dihaloethanes in moderate to high yield (Scheme 9

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• spectra were acquired on Bruker 300 MHz spectrometers equipped with 5 mm BBFO probes. HRMS data were acquired using an Agilent 6530 LC/Q-TOF using a Dual AJS/ESI ion source, and the isotope 79 was used for HRMS analysis for any bromine-containing compounds. Synthesis All procedures and spectra can be

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• the described conditions. The halogen groups on the anilines slightly decreased their reactivity, leading to the formation of products 2q–w with lower yields. However, the 8-chlorine derivative 2u with a o-tolyl aldehyde moiety was prepared with a yield of 37%. Aromatic aldehydes bearing bromine and

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• bromolactonization product 3a. It should be noted that the asymmetric reaction using bromine (Br2) as a brominating reagent gave product 3a in a racemic form. Additionally, iodolactonization of 2a using N-iodosuccinimide in the presence of catalyst (S)-1g was performed. The reaction in dichloromethane, however