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

• , were found. The preferential formation of diastereomers 4a and 5b during the Diels–Alder reaction with the corresponding methylidene adducts was consistent with literature data [24][26]. Next, we studied three-component condensation reactions in the presence of the less active dienes cyclohexadiene

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• -thumb, 1,3-diketones bearing substituents with σm or σp > 0.300 afford meta-anilines from alkylamines in good synthetic yields, and higher σm or σp are required for three-component condensation with less nucleophilic arylamines. The developed one-pot three-component reaction is efficient (yields up to

• calculated Hammett constants of heterocyclic substituents. Previously studied EWGs [53] are shown in the dashed block. The numbers in parentheses are σm and σp calculated [57] constants. Scope of functionalized amines in three-component condensation. Conditions A: 1a,b,h,i (0.2–0.5 mmol), 2e,i–k (0.2–0.75

• EWGs that were previously studied (see Supporting Information File 1). The presence of electron-donating (3ha) or electron-withdrawing groups (3ia) in the aryl substituent of the 1,3-diketone does not affect the reaction outcome (Figure 3). We have further demonstrated the utility of three-component

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

• highly important for the outcome of this reaction. Thus, we decided to significantly improve our approach by optimizing the reaction conditions of a three-component condensation of commercially available 3,4-dimethylaniline (3a, 1.0 mmol), benzaldehyde (4a, 1.0 mmol) and N,N-dimethylbarbituric acid (5

• ’ with a methoxy group in position C(6) in the 1H NMR spectrum when using m-anisidine (3c) only with benzaldehyde (4b, for detailed information, see Supporting Information File 1). It should be mentioned that three-component condensation leading to the formation of 5-aryldeazaflavins 1 usually proceeds

• -aryldeazaalloxazine (2). (C) This work, which describes an efficient three-component method for the synthesis of 2. UV–vis absorption spectra of 5-arydeazaalloxazines 2f, 2j and 2n in DMF (l = 1 cm, c = 2.50 × 10−5 mol·L−1). Three-component condensation of anilines, aldehydes and N,N-dimethylbarbituric acid

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• reaction is a three-component condensation of an α-amino heterocycle (e.g., 2-aminopyridine) 1, an aldehyde 2, and an isonitrile 3 providing the corresponding fused imidazoles (e.g., imidazo[1,2-a]pyridines) of general formula 4 (Scheme 1) [18][19][20][21]. Imidazo[1,2-a]pyridines and related heterocycles

• (sEH) inhibitors [50], HIV-1 non-nucleoside reverse transcriptase inhibitors [51], or potential agents against visceral leishmaniasis [52] were found (Figure 8). Conclusion The Groebke–Blackburn–Bienaymé (GBB) reaction, a three-component condensation of amino heterocycles, aldehydes, and isonitriles

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• are also low in two-stage synthesis methods. The first of them is based on the three-component condensation of aminopyrazoles, Meldrum's acid, and aromatic aldehydes, followed by the oxidation of the intermediate with DDQ [13][16][19] (method B). The second one includes the reaction of an aromatic

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• reaction between the aldehyde and C–H acids followed by the attack of the imidazole N-oxides led to the generation of the final product. In 2020, Valery P. Perevalov et al. introduced one more interesting simple and metal-free three-component condensation methodology for the C-2 functionalization reaction

• -hydroxycoumarin or 1,3-indandione), and aldehyde 33 (2 mmol) in MeCN (5 mL) as solvent was refluxed for 6 h. Three-component condensation reaction of imidazole N-oxides, arylglyoxals, and CH-acids 38 (dimedone, barbituric acid, Meldrum’s acid, 4-hydroxycoumarin, hydroxy-6-methylpyranone, or 4-hydroxy-7,7-dimethyl

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• ), affording a pair of optically active phosphonodepsipeptides 164 and 165 in an 86% yield and 85:15 diastereomeric ratio (Scheme 31) [51]. Following a similar strategy, the three component condensation of diethyl phosphoramidate (166), aromatic aldehydes 167, and diisopropyl (4R,5R)-2-chloro-1,3,2

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• ], anti-inflammatory [8][9], and antiviral [10][11]. The best known methods for the preparation of thiazolopyrimidines are based on condensation reactions. The most commonly used synthesis is the three-component condensation of 2-aminothiazoline, aromatic aldehyde, and ethyl cyanoacetate, which leads to

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• . Thus, a three-component condensation of a series of fluorinated benzaldehydes 50a–h, N-acetyl- or N-benzoylglycine 51a or 51b, respectively, and an excess of acetic anhydride in the presence of sodium acetate afforded the oxazolones 52a–h. The subsequent reductive ring cleavage of 52a–h without

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• ) and Cu(II)@IPSi (1b) was investigated in the one-pot three-component condensation of various benzyl bromides, various phenylacetylenes, and sodium azide (Scheme 1). The authors stated that benzyl azide was formed in situ by the nucleophilic addition of the benzyl bromide and sodium azide. Subsequently

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• –5 min) and reflux of the equimolar amounts of amines 1, para-substituted benzaldehydes 2, and Meldrum’s acid 3 in 2-propanol led to Knoevenagel–Michael adducts 4a–h (Table 1). Beside the short reaction times and mild conditions, this catalyst-free three-component condensation is characterized by a

• . Molecular structure of aminoimidazo[1,2-c]pyrrole 19a according to X-ray diffraction data. Thermal ellipsoids of atoms are shown at 50% probability level. The three component condensation of imidazo[1,2-a]pyridine, aldehydes and Meldrum’s acid described by Gerencsér at al. [31]. Two forms of cation 9i

• . Three forms of the compound 11b in the crystal phase. Synthesis of the mixture of compounds 13 and 14. Resonance structures of 16a. Resonance structures of 19a. Three-component condensation of 2-amino-4-arylimidazoles, aldehydes and Meldrum’s acid. Synthesis of compounds 9b,c,i, 10a, 11b–g. Synthesis of

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• for Ugi reactions because it has two functional groups in its structure. By the way, using bifunctional chemicals in Ugi four-component condensation reaction (4CC) converts it to an Ugi three-component condensation reaction (3CC) and this is identified as an Ugi-4-centre-3-component reaction (U-4C-3CR

Microwave-assisted synthesis of N,N-bis(phosphinoylmethyl)amines and N,N,N-tris(phosphinoylmethyl)amines bearing different substituents on the phosphorus atoms

• Erika Bálint,
• Anna Tripolszky,
• László Hegedűs and
• György Keglevich

Beilstein J. Org. Chem. 2019, 15, 469–473, doi:10.3762/bjoc.15.40

• phosphorus atoms was synthesized by the microwave-assisted and catalyst-free Kabachnik–Fields reaction of (aminomethyl)phosphine oxides with paraformaldehyde and diphenylphosphine oxide. The three-component condensation of N,N-bis(phosphinoylmethyl)amine, paraformaldehyde and a secondary phosphine oxide

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• -aminophosphonate derivatives embrace the Kabachnik–Fields (phospha-Mannich) three-component condensation, where an amine, an aldehyde or ketone and a >P(O)H reagent, such as a dialkyl phosphite or a secondary phosphine oxide react in a one-pot manner [6][7][8][9][10], and the Pudovik (aza-Pudovik) reaction, in

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• -diones. Results and Discussion The required dipolarophiles 1a–c were prepared by the three-component condensation of imidazotriazinethione 2, bromoacetic acid, and aromatic aldehydes (Scheme 2), as was described earlier by us [41]. The starting compound 2 is readily accessible and can be synthesized from

• previously unknown compounds 1d–f were synthesized in good yields by the condensation of imidazothiazolotriazines 5a,b [44] with the corresponding aromatic aldehydes (Scheme 4). These derivatives cannot be prepared by a three-component condensation of imidazotriazinethione with bromoacetic acid and an

Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• Chemistry, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany 10.3762/bjoc.12.146 Abstract A practical method was elaborated for the synthesis of (aminomethylene)bisphosphine oxides comprising the catalyst- and solvent-free microwave-assisted three-component condensation of primary amines

• together with a few by-products could also be identified. Keywords: (aminomethylene)bisphosphine oxides; (aminomethylene)bisphosphonates; microwave; three-component condensation; Introduction Substituted (hydroxymethylene)bisphosphonic acid derivatives form an important group of drugs used in the

• antibacterial, antiparasitic, anticancer and herbicidal activities [5]. (Aminomethylene)bisphosphonates may be prepared in different ways [5]. One of the most convenient and widespread methods is the three-component condensation involving an amine, an orthoformate and a dialkyl phosphite. Usually, primary or

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• , perfluoroalkyl and phosphonate groups, were stereoselectively synthesized through a one-pot three-component condensation of o-phenylenediamines 304, fluorinated alkynylphosphonates 305 and aldehydes 306 (Scheme 63) [101]. The corresponding 1,5-benzodiazepines 307 were isolated in 56–89% yields under optimized

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• salicylaldehydes in a Biginelli-like three-component condensation, two alternative outcomes were observed by Gorobets et al. [18]. When the condensation with acetone was performed in methanol with catalytic amounts of HCl under reflux conditions, a tetrahydrotriazolo[1,5-a]pyrimidine derivative was obtained, while

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• ) consists in the three-component condensation of a 1,3-dicarbonyl compound, an aldehyde, and a nitrogen component, i.e., urea (X = O, R3 = H) or thiourea (X = S, R3 = H) [29]. The use of N-substituted derivatives of urea or thiourea (R3 ≠ H) has also been reported. Recently numerous advances in the

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• , A.V. Bogatsky physico-chemical institute of the National Academy of Sciences of Ukraine, 86, Lustdorfskaya doroga, 65080, Odessa, Ukraine 10.3762/bjoc.10.8 Abstract The regioselective three-component condensation of azomethine ylides derived from isatins and α-amino acids with acrylamides or

• azomethine ylides, generated in situ via decarboxylative condensation of isatins and N-substituted α-amino acids (sarcosine, proline and thiazolidine-4-carboxilic acid) in a three-component fashion. Results and Discussion The three-component condensation of equimolar amounts of isatins 1, α-amino acids 2 and

• acrylamides or aroylacrylic acids afforded regio- and stereoselectively the spirooxindoles 4 and 6 in moderate to good yields. The selectivity of the three-component condensation of isatins and α-amino acids with aroylacrylic acids can be controlled by the reaction temperature and the reaction medium. While

Expedient syntheses of the N-heterocyclic carbene precursor imidazolium salts IPr·HCl, IMes·HCl and IXy·HCl

• Lukas Hintermann

Beilstein J. Org. Chem. 2007, 3, No. 22, doi:10.1186/1860-5397-3-22

• data. Discussion The synthesis of N,N-diarylimidazolium salts according to the Arduengo three component condensation [5] produces strongly colored reaction mixtures, from which the products are obtained as impure raw materials. [5][6][7][8][11] The biphasic aqueous/organic reaction conditions of that

Microwave assisted synthesis of triazoloquinazolinones and benzimidazoquinazolinones

• Aboul-Fetouh E. Mourad,
• Ashraf A. Aly,
• Hassan H. Farag and
• Eman A. Beshr

Beilstein J. Org. Chem. 2007, 3, No. 11, doi:10.1186/1860-5397-3-11

• triazoloquinazolinones and benzimidazoquinazolinones. The reaction involves a three component condensation (with potential for combinatorial work) being carried out with almost productive yields by microwave irradiation and considerably shortened reaction time. Background Condensed heterocyclic systems with a partially

• triazoloquinazolinones and benzimidazoquinazolinones. The reaction involves a three component condensation (with potential for combinatorial work) being carried out with almost productive yields by microwave irradiation and considerably shortened reaction time (This conclusion was suggested by the referee.). Synthesis

Cobalt(II) chloride catalyzed one-pot synthesis of α-aminonitriles

• Surya K. De

Beilstein J. Org. Chem. 2005, 1, No. 8, doi:10.1186/1860-5397-1-8

• three- component condensation of aldehydes, amines, and potassium cyanide in acetonitrile in the presence of a catalytic amount of CoCl2 at room temperature. Introduction The addition of cyanide to imines (the Strecker reaction) [1] provides one of the most direct and viable routes for the synthesis of