Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• sample synthesized by a conventional method. Conclusion The synthesis of biologically relevant 6-aryl/heteroaryl-N2-(5H-tetrazole-5-yl)-5,6-dihydro-1,3,5-triazine-2,4-diamines was achieved under controlled microwave heating via a simple one-pot, three-component reaction of cyanamide 1, aldehydes 2, and 5

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• , and trifluoromethyl they smoothly took part in the three-component reaction and provided the desired products 6ja–na in moderate yields. It is noteworthy that benzaldehydes containing a halogen atom such as fluorine, chlorine, bromine, and iodine in the para and meta-positions were also compatible

• three component reaction of benzaldehyde, thiourea, and orthoformates. Reactions were performed with benzaldehyde (1.0 mmol, 1.0 equiv), thiourea (2.5 mmol, 2.5 equiv), orthoformates (1.0 mmol, 1.0 equiv) in 1 mL DMF at 80 °C for 5 h; yields refer to isolated yields. Gram-scale synthesis of 6aa. Control

• -component reaction of aldehydes, thiourea and trimethyl orthoformate. Reactions were performed with aldehydes (1.0 mmol, 1.0 equiv), thiourea (2.5 mmol, 2.5 equiv), trimethyl orthoformate (1.0 mmol, 1.0 equiv) in 1 mL DMF at 80 °C for 5 h; yields refer to isolated yields. Orthoformate substrate scope of the

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• reactions to make it a green synthetic method with pot, atom and step economy (PASE) [55][56]. Results and Discussion Following the reported procedures for amino ester- and amino acid-based [3 + 2] cycloaddition reactions, pyrrolidine adducts 5 and 6 were synthesized by a three-component reaction of 1 or 2

• achieved by the combination of a three-component reaction with one-pot reactions. This synthetic sequence is a new addition of our [3 + 2] cycloaddition-initiated reactions for making diverse cyclic scaffolds. Experimental General procedure for the synthesis of pyrrolidine adducts 5 A solution of amino

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

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• cleavage of the bond between the N-4 and C-benzene in thiadiazine ring-type molecules [9]. To date, only few examples of copper-based catalysts have been reported to enable access to such compounds [10][11][12][13]. Chang and co-workers were pioneers in this area [10][11][12]. A three-component reaction

• ]. Based on these earlier results, the reactivity of these catalysts was investigated in the context of achieving formation of the challenging sulfonamide derivatives. Herein, we report the high efficiency of cationic copper(I) complexes for the formation of N-sulfonylamidines via a three-component

• reaction performed in air, using solvent-free conditions and in the absence of any additive. Results and Discussion [Cu(ICy)2]BF4 (1), [Cu(IPr)(ICy)]BF4 (2) and [Cu(IPr)(Pt-Bu3)]BF4 (3) were initially selected as optimum candidates [22]. This class of catalysts was expanded through the synthesis of the

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• , which had been obtained earlier [5] by the three-component reaction of starting materials 1c, 2a–f, and 3a (HOAc, 65 °C, 48 h). This instability complicated the isolation and characterization of the heterocycles 4p–u. The condensation of compounds 1c, 2a–f, and 3a in dry DMF under otherwise identical

• 35%). The same carboxylic acid 7 was obtained by counter synthesis through a three-component reaction involving 5-aminopyrazole-4-carbonitrile (1a), 4-methoxybenzaldehyde (2b), and pyruvic acid (3a) under heating at reflux in acetic acid for 240 min (yield 28%) or through two-component

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• and co-workers, who developed a one-pot, three-component reaction to produce protected homoallylic amines 4 (Scheme 1) [19]. It was reasoned that adaptation of the Veenstra protocol would allow us to introduce a second alkene unit during the same process, thus generating a ring-closing metathesis

One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines

• Valeriya G. Melekhina,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Vitaly S. Mityanov,
• Artem N. Fakhrutdinov,
• Arkady A. Dudinov,
• Vasily A. Migulin,
• Yulia V. Nelyubina,
• Elizaveta K. Melnikova and
• Michail M. Krayushkin

Beilstein J. Org. Chem. 2019, 15, 2840–2846, doi:10.3762/bjoc.15.277

• amines 3 did not only furnish the desired scaffolds in satisfactory yields but also allowed to use a variety of readily available substituted substrates (Scheme 1). Results and Discussion The published synthesis of acetamides 2 includes a one-pot three-component reaction of 4-hydroxy-6-methyl-2H-pyran-2

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• equivalents) was added to a solution of PPh3 and an active methylene compound 2a–c,e,f, a 1:1:1 three-component reaction occurred smoothly within 0.5–6 hours and yielded the phosphonium-1,5-betaines 3a–o in mostly high yields (Scheme 3 and Figure 1). Meldrum’s acid (2a), N,N’-dimethylbarbituric acid (2b), 1,3

• in transamidation reactions with nucleophilic amines [18][22]. Therefore, it was interesting to know the performance of propiolic acid chlorides in the same betaine syntheses. We found that acid chlorides 4 indeed underwent the three-component reaction with N,N’-dimethylbarbituric acid and furnished

• ]. Conclusion We have observed that the reaction of N-triflyl-N-phenylpropiolamides with triphenylphosphane results in undefined polymerization and formation of N-phenyltriflamide. In the presence of several active methylene compounds, however, a clean three-component reaction leads to a novel type of

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• , Ukraine Bar-Ilan University Ramat Gan, 5290002, Israel 10.3762/bjoc.15.231 Abstract The three-component reaction of 5-aminotetrazole with aliphatic aldehydes (formaldehyde, acetaldehyde) and acetoacetic ester derivatives in water under microwave irradiation leads to the selective formation of 4,7

• ] comprises the three-component reaction of amine 1 with the synthetic precursors of the unsaturated ketone 2 (Scheme 1, reaction 2), i.e., carbonyl compound 4 and a methylene-active compound 5. These approaches are general and useful for the preparation of variety of dihydroazolopyrimidines which is easily

• 1,3-dicarbonyl compound was observed in the three-component reaction. Reacting it with amine 1 and aldehyde 7a under conditions similar to those for acetoacetic esters (8a–d) led to formation of a mixture of compounds 11 and 12 (Scheme 3). Heteroaromatic tetrazolopyrimidine 11 was obtained as a single

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• -bromophenyl)imidazole (1i) with Se powder gave the corresponding tricyclic product 10 in low yield. Since the reaction conditions for the synthesis of the starting material 1 and the cyclization of 1 with Se powder are similar, we carried out a three-component reaction of benzimidazole, 1-bromo-2

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• the use of toxic reagents and solvents, harsh reaction conditions and long reaction times. The use of a heterogeneous catalyst and water made this method a green and sustainable approach for organic transformations. This transformation involved the well known three-component reaction of 3 with 1 and 2

• might be due to the formation of Cu(II)-mediated propargylamine 68 from the alkyne and Schiff base-copper complex that was cyclized and aromatized to form the target compound 67 (Scheme 24). Kumar et al. have described a Cu(OTf)2-catalyzed three-component reaction for the synthesis of imidazo[1,2-a

• ]pyridines under microwave irradiation [115]. 1-Butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) was used as ionic liquid for this three-component reaction of pyridine-2(1H)-one 70, acetophenone 71 and o-tosylhydroxylamine (72, Scheme 25). The reason behind the use of an ionic liquid as reaction

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• ][87] and reactions involving sulfur [88], herein, we describe a novel synthesis of O-thiocarbamates and dithiocarbamates via a three-component reaction of elemental sulfur, isocyanides and alcohols or thiols (Scheme 1). Moreover, during the investigation of the reaction mechanism, we have identified

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• different reaction pathways were applied based on known synthetic procedures (Scheme 2): the three-component reaction between pyruvic acid (1), aromatic aldehydes 2a,b and 5-amino-3-methylpyrazole (3) (HOAc, Δ, 30 min) [45] and a two-component condensation of the preliminary synthetized 4-(4-methoxyphenyl

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• transformations used in steroid modification, in the last years various MCRs have emerged as suitable procedures for the diversification of this family of biomolecules. A remarkable example is the report of Iglesias-Arteaga and co-workers [34] on the application of the Pd(II)-catalyzed three-component reaction

• ]. Synthesis of ecdysteroid derivatives by Ugi-4CR using a steroidal isocyanide [30]. Stereoselective multicomponent synthesis of a steroid–tetrahydropyridine hybrid using a chiral bifunctional substrate and a cholestanic isocyanide. DBA: 3,5-dinitrobenzoic acid [31]. Pd(II)-catalyzed three-component reaction

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• equivalents of 2-formylbenzoic acid (33) in an Ugi three-component reaction with methanol as solvent at room temperature to afford tetrahydrodiisoindoloquinoxalinecarboxamides 43 (Scheme 12). More recently, Shafiee et al. [90] utilized propargylamine as the cycle-nitrogen delivering component and then

• three-component reaction between aryl iodides, incorporating a Michael acceptor 105, amines and amides 2 and carbon monoxide (23) (Scheme 30) [108]. It is remarkable that not only aromatic but also aliphatic amines and even amides and sulfonamides can be used as the nitrogen-containing substrate. With

• -methyleneoxindole derivatives (Scheme 31) [109]. In this three-component reaction, 2-ethynylanilines 109 reacted with carbon monoxide (23) and perfluoroalkyl iodides 110, in the presence of Pd(II) and phenylboronic acid (111), by means of an intramolecular amino-carbonylation reaction. Although phenylboronic acid

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• .15.103 Abstract A three-component reaction involving in situ generation of propargylureas and subsequent Zn(OTf)2-mediated cyclocondensation with a primary amine yielded trisubstituted 2-aminoimidazoles. These findings are in contrast to the previously reported base-promoted unimolecular cyclization of

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

• -bielectrophiles or their synthetic precursors in the case of three-component reactions between these amines, carbonyl compounds and CH acids. Previously, an unusual direction of the three-component reaction between 2-aminoimidazoles, aldehydes and 5,5-dimethyl-1,3-cyclohexanedione has led to the formation of the

• aminoazole fragments. In all earlier described experiments with participation of different α-aminoazoles as binucleophiles the reaction cascade readily accomplished by the formation of fused heterocyclic systems [25]. An analogous three-component reaction involving indole or imidazo[1,2-a]pyridine

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• base-catalyzed cyclization reaction is reported. The synthesis was carried out through a three-component reaction of (arylhydrazono)methyl-4H-chromen-4-one, malononitrile, primary amines in the presence of Et3N at room temperature. However, carrying out the reaction under the same conditions without

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

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• Institute of Engineering Science and Technology, Shibpur, PO-Botanic Garden, Howrah-711 103 (WB), India 10.3762/bjoc.15.61 Abstract The LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this

• pattern of the allene – a remarkable variety of reactions and product types are known using the three-carbon backbone of these reactive compounds [10]. During the exploration of alkoxyallene chemistry [11][12][13][14][15][16][17][18][19][20] we accidently discovered a new three-component reaction leading

• to β-ketoenamides that are uniquely functionalized alkenes and suitable for a variety of subsequent reactions, in particular in heterocyclic synthesis. This LANCA three-component reaction (LA = lithiated alkoxyallene, N = nitrile, CA = carboxylic acid) was observed for the first time by Oliver Flögel

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

• ) and a secondary phosphine oxide react in a condensation reaction [1]. However, only a few papers deal with the synthesis of α-aminophosphine oxides. (Phenylaminomethyl)dibenzylphosphine oxide was prepared by the three-component reaction of aniline, paraformaldehyde and dibenzylphosphine oxide [7], as

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• three-component reaction of o-iodoanilines and K2S in DMSO [20]. Another way to prepare 2-mercaptobenzothiazoles and 2-mercaptobenzoxazoles is the nucleophilic substitution of 2-halo-substituted benzothiazoles and benzoxazoles with sulfur-containing reagents including sodium thiosulfate [21], thiourea

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• Chemistry, North Caucasus Federal University, Pushkin st. 1a, 355009 Stavropol, Russian Federation 10.3762/bjoc.14.287 Abstract The sequential three-component reaction between o-hydroxybenzaldehydes, N-(cyanomethyl)pyridinium salts and a nucleophile towards substituted chromenoimidazopyridines under

• as optimal conditions), probably due to improved solubility of manganese salt. To understand the scope of this three-component reaction of nitromethane, the optimized conditions were used with different o-hydroxybenzaldehydes to prepare products 5a–h with 37–68% yields, displaying tolerance to

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• -aminopyrazoles under iodine-catalyzed three-component reaction was not described so far. In view of this, we present a direct and selective multicomponent strategy to synthesize 5-amino-4-(arylselanyl)-1H-pyrazoles 4 by reacting benzoylacetonitrile derivatives 1, arylhydrazines 2 and diorganyl diselenides 3