Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• , IACT-CSIC. Avda. de las Palmeras 4, 18100 Armilla (Granada), Spain 10.3762/bjoc.22.63 Abstract The reactivity of isatin toward ethylenediamine displays an unexpected stoichiometric divergence, affording either the anticipated diiminoisatin or a previously unreported pentacyclic bis-spirooxindole. A 2

• conditions. Keywords: ethylenediamine; isatin; spirooxindole; Introduction Isatin (1) is a highly versatile platform for heterocycle construction, particularly through skeletal editing, ring expansion, and related transformations that enable rapid access to complex molecular architectures [1]. In parallel

• . In this context, we turned our attention to the reaction of isatin with unsubstituted ethylenediamine. Although analogy with related diamines would suggest preferential diiminoisatin formation, our results reveal a pronounced divergence in reactivity under different conditions, prompting a detailed

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• conversion was obtained with respect to the reaction involving triethylamine (Table 2, entries 2 and 3). Upon employing ethylenediamine, the conversion dropped to 26% (Table 2, entry 4). This may be due to the chelating behavior of this amine. Indeed, ethylenediamine can strongly coordinate the metal center

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• ethylenediamine [27] as well as with 2-(aminomethyl)aniline and 1,3-diaminopropane [28]. In addition, we have found another route for the three-component cyclization of 3-polyfluoroalkyl-3-oxo esters with α-methylene ketones involving mono- and dialkylamines, leading to 5-polyfluoroalkylaminocyclohexen-2-ones [29

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• condensation-type reaction using ethylenediamine (EDA) as catalyst in AcOH under microwave (μw) heating. This convenient methodology is broad in scope, provides the condensation products in high yields (up to 99%), with a reasonable catalyst loading (10 mol %) in only 30 minutes. This approach also enabled the

• -benzylidenethiazol-4-one (3’) in moderate yield (Scheme 1). The implications and scope of this finding will be published in due course. Switching to aromatic (pyridine) or tertiary amines (Et3N) resulted in low yields (Table 1, entries 11 and 12). In contrast, the use of ethylenediamine (EDA) stood out, delivering

• decrease in yields (Table 1, entries 19–21). To confirm the critical role of ethylenediamine in the reaction mechanism, an experiment without its presence was conducted, resulting in only 2% of the desired product (Table 1, entry 22). With the optimized reaction conditions established, this methodology was

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• polyethyleneimine derivatives by coupling ethylene glycol and ethylenediamine using manganese-pincer catalyst Mn1 (1 mol %), t-BuOK (10 mol %) in toluene at 150 °C (Scheme 21) [48]. The mechanistic investigation based on the experimental and DFT calculations suggested a BH pathway. First, dehydrogenation of the

• ethylene glycol followed by condensation with ethylenediamine generated the corresponding imine intermediates. The subsequent hydrogenation with borrowed hydrogen finally formed the polyethyleneimine product. In 2023, Royo and co-workers conveyed the N-alkylation of amines with alcohols using the bis

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• research group explored the activity of cadmium sulfide (CdS) nanotubes as heterogeneous nanocatalysts for the electrophilic condensation between aldehydes and indoles [106]. The nanorods were obtained with a solvothermal technique, where thiourea and cadmium nitrate were mixed in ethylenediamine for 10

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• equiv) dissolved in MeCN (5 mL) were added dropwise during 12 hours by using a push-syringe. The mixture was stirred for 48 hours at room temperature. The solvent was evaporated and the residue was dissolved in DCM (25 mL), followed by washings with N-(2-hydroxyethyl)ethylenediamine-N,N′,N′-triacetic

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• nitrotoluene (22) under alkaline conditions (e.g., O2, KOt-Bu; O2, KOH, MeOH, ethylenediamine, etc.), as reported by Stansbury and Proops [33]. Aerobic oxidation of 22 in alkaline methanol with added ethylenediamine, gave 21 in 36% yield (Scheme 2), which is poor compared to that reported for the p-nitro

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• ethylenediamine monohydrochlorides were grinded with a half equivalent of 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (blue moieties in Scheme 2) for 10 minutes. The synthesis of diamine monohydrochlorides and characterization data of mono-imine ammonium salts were

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• recrystallized to obtain the enantiomerically pure ʟ-menthyl ester 35a (Scheme 8). Milton et al. [47] synthesized the key intermediate 38 by two synthetic routes. The first route involves a reaction of bromoacetaldehyde diethyl acetal (36) with a xanthate ester, followed by treatment of ethylenediamine, which

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• significant improvement in Tm was observed when the functionalizing groups were changed from ethylenediamine to either trimethylenediamine (monomer 42) or putrescine (monomer 43), demonstrating that the length between the cationic amino group and the sugar scaffold is important for the thermal stability

• 74) (DMAP) [107], and the other the N,N-diethyl-ethylenediamine phosphoramidate linkage (75) (DEED) [108]. Stereo-uniform ONs (either Rp or Sp) containing the DMAP modification were synthesized via dinucleotide derivatives obtained by a phosphitylation reaction followed by oxidative amidate coupling

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• –dsRNA triplexes [74]. γ-Modified PNA: Later studies focused on introducing substituents in the ethylenediamine moiety of the PNA backbone. Ly and co-workers showed that introduction of simple substituents, such as methyl (derived from ʟ-alanine) or hydroxymethyl (derived from ʟ-serine) at the γ-position

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• (DEG), dipropylene glycol (DPG)) aminolysis (2-aminoethanol, 3-amino-1-propanol, ethylenediamine). Advantages of catalytic processes are obvious and can be witnessed in the hydrolysis and the glycolysis reactions of poly(ethylene terephthalate) (PET) [82][83]. Representative data are reported in

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• -aminophthalazinones, we decided to investigate how these compounds behave towards Cu(II) ions. For testing, we chose the derivatives of ethylenediamine 6d, N-phenylpyridin-2-amine 5i, and additionally the pyridin-2-yl derivative 7 (Figure 3). Compound 7 was synthesized according to the method described by us [43

• ]. All selected compounds (Figure 3) contain some specific structural elements (e.g., an ethylenediamine moiety, similarity to bipyridyl or even to isocyclam skeleton) allowing them to act as ligands and form complexes. In our tests, we hoped that putting in the 4-position of the skeleton a substituent

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• -tetraazacyclotetradecane), cyclen (1,4,7,10-tetraazacyclododecane)), ethylenediamine and triethylenetetraamine derivatives. Studies of Au(III)-cyclam modified complexes have been limited to arylated [16] or polymer-bound cyclams for selective uptake of Au(III) from water [17] as well as X-ray crystal structures [18][19

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• . After the treatment of (−)-46 with the lithium acetylide ethylenediamine complex in THF, a nucleophilic alkynylation occurred, with a reversal of configuration in the reaction center. Then, removal of the 1-(2-hydroxyphenyl)ethyl group via cleavage of the C–N bond, leading to (6S)-ethynylpiperidine

• occurred by removing the TBDMS and formyl (CHO) groups via treatment with TBAF in dry THF and lithium–ethylenediamine complex, respectively. Finally, the resulting alcohol (+)-56 was oxidized in the presence of PCC to provide (−)-adaline (1). In this work, the quaternary center was successfully generated

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• connection to the crown ether core, and in NDIC7, a more flexible ethylenediamine linker is used. Crown ether synthesis and crystal structures With respect to the synthesis of previously reported TTFC8 and exTTFC8 [35][37], we synthesized the novel 21-crown-7 analogs following a similar synthetic route

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• ethylenediamine (2 equiv) was added to 1,4,5,8-naphthalenetetracarboxylic dianhydride (1, 1 equiv) in dry DMF. The mixture was stirred for 15 h at 90 °C. The crude product was extracted into the organic (chloroform) layer and concentrated under vacuum. The crude product was further purified by column

• adjacent amino groups (pH 7, green) and decorated by two GCP arms protonated at pH 5 (red; pH-switchable DNA groove binders). Synthesis of compound 4. Conditions: a) mono-N-Boc-ethylenediamine, DMF, 90 °C; b) i) trifluoroacetic acid (TFA)/CH2Cl2 1:1, ii) Fmoc-Lys(Boc)-OH, DIPEA, HCTU; c) i) TFA/CH2Cl2 1:1

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• co-workers [39] used a comparatively simple ligand to perform asymmetric silylations of imines. Different ethylenediamine-based ligands (L3–L5) were screened from which L3 proved to give even better yields and ees (Scheme 13). The use of this ligand was explored with other substrates 56 and found to

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• the target molecule. First, the phthalimido group was removed using ethylenediamine [26] followed by acetylation with Ac2O in the presence of pyridine [27] to furnish the desired acetamido functionality. Next, the benzylidene group was hydrolyzed using 80% AcOH at 80 ºC [28]. Further, Zemplén de-O

1,2,3,4-Tetrahydro-1,4,5,8-tetraazaanthracene revisited: properties and structural evidence of aromaticity loss

• Arnault Heynderickx,
• Sébastien Nénon,
• Olivier Siri,
• Vladimir Lokshin and
• Vladimir Khodorkovsky

Beilstein J. Org. Chem. 2019, 15, 2059–2068, doi:10.3762/bjoc.15.203

• ]. A strongly fluorescent compound, 3, has been isolated from the reaction of ethylenediamine with noradrenaline, 2-methylnoradrenaline, adrenolone, 3,4-dihydroxymandelic acid or catechol [8]. The reaction with 2,5-dihydroxy-p-benzoquinone (4) under a stream of air affording 3 in 50% yield was proposed

• THTAA Derivative 3 was prepared from 2,5-dihydroxy-p-benzoquinone and ethylenediamine as brownish-yellow solid according to the recommended procedure (Scheme 1) [8]. Crystallization from butyl acetate produced yellow crystals of THTAA (3) in about 50% yield, still slightly brownish, along with the

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• ) and ethylenediamine (5). Subsequently, to the same pot appropriate metals were added to obtain the respective complexes 7 [55]. In 2002, Otera and co-workers reported the formation of some supramolecular self-assembled structures which was found to be faster under solvent-free mechanochemical

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• -chlorobenzamide 13. Removal of the Boc-group with TFA resulted in 14. Next, the phthalimide was removed via refluxing with ethylenediamine and the resulting amine protected as para-nitrobenzenesulfonamide to obtain the desired fragment 9. The synthesis of 10 starts from commercially available 2-methylene-1,3

• the target analogues. Synthesis of fragment 9. Reagents and conditions: a) phthalimide, Pd2(allyl)2Cl2, ligand 15, Na2CO3, CH2Cl2, rt; b) i) 13, DEAD, PPh3, toluene, 0 °C to rt; ii) TFA, CH2Cl2, H2O, rt; c) i) ethylenediamine, EtOH/THF 7:3, reflux; ii) p-Ns-Cl, Et3N, THF, 0 °C. Synthesis of fragment