Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• acid (DHB) or (2-methylprop-2-en-1-yliden)malononitrile (DCTB) as the MALDI matrix. Elemental analyses were performed on a Flash 2000 Organic Elemental Analyser (Thermofisher). For samples containing chlorine mercurimetric titration was used. IR spectra were recorded on a Nicolet iS50 equipped with an

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• 2205 cm−1 for product 5c. These results differ from the absorption in the range of 2260–2240 cm−1, which would be characteristic for a cyano group attached to sp3-hybridized carbon [82]. On the other hand, 13C NMR shifts of the C(2’’) position of purine–malononitrile conjugate 5a and ethyl cyanoacetate

• -1-yl)-1,9-dihydro-6H-purin-6-ylidene)malononitrile (5a): Under argon atmosphere to a suspension of 9-heptyl-2,6-bis(4-phenyl-1H-1,2,3-triazol-1-yl)-9H-purine (2c, 141 mg, 0.28 mmol, 1 equiv) in anhydrous DMF (2.5 mL) malononitrile (23 mg, 0.35 mmol, 1.3 equiv) and NaH (8 mg, 0.34 mmol, 1.2 equiv

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• was discussed previously [29]. The reaction of 4 with malononitrile-derived gem-dithiolate (5b, Scheme 1, route 2) also proceeded under mild conditions in DMF and bicyclic o-quinone 6b was obtained in a good yield. The brown crystals suitable for X-ray analysis were grown from an acetone/diethyl ether

• mixture. X-ray diffraction data revealed that the bond lengths distribution in the six-membered ring of 6b is typical of sterically hindered o-quinones. The annulated fragment including the 1,3-dithiole cycle and the malononitrile unit is almost flat. The six-membered o-quinone ring is distorted due to

• phase. In order to attach the 1,3-diketonate moiety to the periphery of the o-quinone molecule, we treated the o-quinone 4 with sodium gem-dithiolate obtained from acetylacetone (5d, Scheme 1, route 2). Unlike interactions with sodium trithiocarbonate or malononitrile gem-dithiolate, the o-quinone 6d

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• malononitrile under catalyst-free conditions have been reported [29]. Wang et al. reported the functionalization of benzylic C–H bonds of 2-methylazaarenes by nucleophilic addition to aromatic aldehydes catalyzed by acetic acid using harmful chlorinated solvent, and this reaction suffers from longer reaction

Styryl-based new organic chromophores bearing free amino and azomethine groups: synthesis, photophysical, NLO, and thermal properties

• Anka Utama Putra,
• Deniz Çakmaz,
• Nurgül Seferoğlu,
• Alberto Barsella and
• Zeynel Seferoğlu

Beilstein J. Org. Chem. 2020, 16, 2282–2296, doi:10.3762/bjoc.16.189

• employed to gain insight into the experimental data. Results and Discussion Synthesis As depicted in Scheme 1, dye 2 was obtained in good yield by reacting malononitrile and 4-aminoacetophenone (compound 1) according to our previous published procedure [31][32]. The styryl-based organic chromophores 3–7

• 2 was published previously [31][32]. Dyes 3–7 were synthesized using 2 and the appropriate benzaldehyde. Equimolar (3 mmol) amounts of 2-(1-(4-aminophenyl)ethylidene)malononitrile (2) and the appropriate benzaldehyde derivative in 20 mL of ethanol were refluxed for 2 h. A colored solid formed for

• all dyes 3–7 which was collected by filtration and recrystallized from ethanol to obtain the pure dyes. ((E)-2-(1-(4-Aminophenyl)-3-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)allylidene)malononitrile) (3) Dark purple solid; yield: 64%; mp 236–238 °C; FTIR (cm−1): 3441, 3349, 3224, 2920

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• -ranging biological activities [62][63]. The most common synthetic route for the preparation of 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines is the condensation reaction of aldehydes, malononitrile, and thiols in the presence of a variety of catalysts [64][65][66][67][68][69][70][71][72]. Though the

• purpose, a control experiment in the absence of a catalyst was conducted by using the model substrates benzaldehyde (2a, 1.0 mmol), malononitrile (8, 2.0 mmol), and 2-mercaptopyridine (9, 1.0 mmol) in H2O (3.0 mL) under ultrasound irradiation at 45–50 °C for 60 min. It was observed that the reaction did

• was increased from 30 to 40 min. The optimized procedure was successfully applied for the synthesis of a series of highly substituted pyridines (11b–r, Table 7) by utilizing a range of (hetero)aromatic aldehydes 2, malononitrile (8), and the thiols 9 and 10, respectively, as starting materials

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• ). Alkyl-substituted derivatives proved to be similarly successful substrates; however, the TMS-substituted derivative was obtained in a significantly lower yield. In terms of linkers, heteroatoms were well-tolerated, although the use of malononitrile resulted exclusively in the elimination product despite

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• epoxidation agent of an electron-deficient olefin intermediate, which was formed by deaminative Mannich coupling between the imine and nucleophiles such as malononitrile and methyl cyanoacetate (Scheme 64) [109]. Overall, a variety of additional examples of porphyrin-photocatalyzed heteroatom oxidations are

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

• -indanedione (2c), malononitrile (2e), 4-cyanomethyl-2,3,5,6-tetrafluorobenzonitrile (2f) were successfully applied as active methylene compounds; all of them have pKa values between 4.70 (2b, in dioxane/H2O 3:1 [20]) and ≈15.80, reported for 2-(pentafluorophenyl)acetonitrile in DMSO [21], the value for 2f

• , which reacted with PPh3 and malononitrile to furnish the desilylated betaine E-3o; the required proton probably stems from the adventitious presence of water (Scheme 4). Notably, 3o could not be obtained directly from the 3-H substituted N-triflylpropiolamide 1g. Some betaines 3 were isolated solely as

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

• androstanic steroids. Such heterocyclic moieties are of interest because of their pharmacological activity, for example, as anti-inflammatory agents. Employing epiandrosterone and benzaldehyde as oxo components, ammonium acetate and malononitrile as C-nucleophile, the authors produced 2-amino-3-cyano-1,4

• -dihydropyridine 46 fused to the androstane at positions 16 and 17 (Scheme 14). The MCR proceeds by the condensation of malononitrile with benzaldehyde to form the benzylidene malononitrile adduct, and of the ketosteroid with ammonium to form the steroidal enamine, which cyclizes with the benzylidene to furnish

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

• acyclic CH acids. As the last compounds we have used Meldrum’s acid, malononitrile and ethyl 2-cyanoacetate. Results and Discussion In view of the structure of 2-amino-4-arylimidazoles containing four nonequivalent nucleophilic centres several pathways can be assumed for their reactions with carbonyl 1,3

• active compounds, that can lead to cyclic products, has a high potential for diversity-oriented synthesis. In the three-component condensations of equimolar amounts of 2-amino-4-arylimidazoles 1, para-substituted benzaldehydes 2 and malononitrile (12) in 2-propanol the Knoevenagel–Michael adduct was not

• -arylimidazole 1 (1.0 mmol), aromatic aldehyde 2 (2.0 mmol) and malononitrile 12 (1.0 mmol) in 2 mL of 2-propanol was refluxed during 20–30 min. After cooling, the yellow solid products 14 were filtered off and crystallized from iPrOH. 14a: yellow powder, 65%; mp 221–222 °C; 1H NMR (200 MHz, DMSO-d6) δ 9.34 (s

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

• construct fused heterocyclic skeletons [37][38][39][40], we describe the synthesis of pyrazolopyridines 4a–m containing a chromone moiety (Scheme 1). The synthetic approach was based on a domino reaction of (arylhydrazono)methyl-4H-chromen-4-one 1a–g, primary amines 2a–c, and malononitrile (3) in the

• phenylhydrazine [42][43]. Subjecting (arylhydrazono)methyl-4H-chromen-4-one (1a), benzylamine (2a), and malononitrile (3) in the presence of 40% triethylamine was stirred at room temperature in ethanol. Compound 4a was precipitated and filtered. After confirmation of the structure, we tried to find a suitable

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• -inflammatory [5], and antidiabetic agents [6]. The numerous known methods for the preparation of these compounds are generally based on multicomponent reactions of an aromatic aldehyde, a β-keto ester, a hydrazine and malononitrile [7]. In a similar reaction using a pyridinium ylide instead of malononitrile

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• four-component reaction of cyclic/acyclic ketones, malononitrile, aromatic aldehyde and ammonium acetate affording 2-amino-3-cyanopyridine derivatives have been explored extensively [45][46][47][48][49][50][51][52][53][54][55]. However, syntheses of pyridine scaffolds bearing an indole side chain have

• –C bond forming reaction [57] and three-component reactions of aromatic aldehydes, 3-(1H-indol-3-yl)-3-oxopropanenitrile and malononitrile [58][59], 2-acetylpyridine [60] or 3-amino-2-enones [61]. Incidentally, the indole scaffold is found in several natural products and bioactive synthetic compounds

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• ), and 1-naphthol (34d)), and malononitrile (35) in water at 90 °C. Isatin (32) and acenaphthenequinone (33) were reacted with C–H activated acids 20a,b, 23, and 34a–c and malononitrile (35) to form the corresponding spiro-isatin derivatives 36 and spiro-acenaphthenequinone derivatives 37 under mild and

• , 34a–c and malononitrile (35) under the same reaction conditions. The observations showed that bis(2-amino-4H-pyran) derivatives 39–44 are constructed in excellent yields during very short reaction times with a higher amount of the catalyst (4 mol %, Scheme 6). The recyclability of this homogeneous

• catalytic system was also studied by the reaction of isatin, malononitrile, and dimedone. After completion of the reaction, the reaction mixture was filtered and the same substrates were added directly to the filtrate solution containing the homogeneous catalytic system. There is no need to add solvent as

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• sample at 50 Hz repeating rate. Time-of-flight mass analyses were performed in the reflection mode at a resolution of about 10 000. The matrix, trans-2-(3-(4-tert-butylphenyl)-2-methyl-2-propenylidene)malononitrile, was prepared as a 40 mg/mL solution in chloroform. The matrix solution (1 μL) was applied

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• to the synthesis of benzofulvalanes 49 and 50 from the reaction of 4,5-benzotropone (11) with corresponding cyclopropanes [60][61]. While the reaction of 4,5-benzotropone (11) with malononitrile afforded 8,8-dicyano-3,4-benzoheptafulvalene (51) [62], the condensation of 4,5-benzotropone (11) with

• for 2,3-benzotropone (12) are condensation reactions with active methylenic compounds, resulting in the formation of benzoheptafulvenoids (Figure 6). For example, Machiguchi reported that the condensation reaction of deuterium tracer 2,3-benzotropone 177 with malononitrile to yield 8,8-dicyano-2,3

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• Mannich bases with malononitrile catalysed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) [67]. It is known that the use of quaternary ammonium salts offers the easier removal of the amino residue and, therefore, trapping the transient electrophilic species at lower temperature. Carrying out the reactions in

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

Mechanochemical Knoevenagel condensation investigated in situ

• Sebastian Haferkamp,
• Franziska Fischer,
• Werner Kraus and
• Franziska Emmerling

Beilstein J. Org. Chem. 2017, 13, 2010–2014, doi:10.3762/bjoc.13.197

• .13.197 Abstract The mechanochemical Knoevenagel condensation of malononitrile with p-nitrobenzaldehyde was studied in situ using a tandem approach. X-ray diffraction and Raman spectroscopy were combined to yield time-resolved information on the milling process. Under solvent-free conditions, the reaction

• synthesis in which bases or Lewis acids are used as catalysts, Kaupp et al. could reduce the amount of catalysts [21]. The Knoevenagel condensation of p-nitrobenzaldehyde with malononitrile was initially only accessible in melts at 150–170 °C or in the presence of a catalyst like calcite or fluorite [21][22

• ]. In an extended study, including different aldehydes, Ondruschka et al. reported a solvent- and catalyst-free Knoevenagel condensation of p-nitrobenzaldehyde and malononitrile in a vibrational mill [23]. Here, we report the first direct in situ investigation of a Knoevenagel condensation followed by

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• advantages of the nitrile functional group before its removal. Mechanistic details and applications to organic synthesis are provided. Keywords: α-aminonitrile; decyanation; electron donor; hydride; malononitrile; transition metal catalysis; Introduction Many strategies in organic synthesis involve the

• substituted carbocycles [119][120]. An example in described in Scheme 22. The 5-membered ring is formed via a K2CO3 mediated SN2 – conjugate addition sequence between malononitrile and 6-bromo-2-hexenoate derivatives 67a,b. Dicyanocyclopentanes 68a,b are treated with tributyltin hydride/AIBN giving the

• dinitriles and applied this reaction for the synthesis of new NHC-boryl nitrile and dinitrile compounds [121]. They observed that malononitrile was the most efficient donor to produce boryl nitriles and concluded that substituted malononitriles would be decyanated by NHC-boranes. For this transformation

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

• ZnO nanorods-catalyzed reaction of isatin derivatives 144 with malononitrile (145) and dialkyl or diphenyl phosphonates 146 has been performed to give 2-oxindolin-3-ylphosphonates 147 (Scheme 31) [56]. The products were obtained in good to excellent yields using 10 mol % of the catalyst under solvent

• -free conditions at room temperature. However, when using ethyl cyanomalonate instead of malononitrile, the reaction in water led to the corresponding 2-oxoindolin-3-ylphosphonate in good yield. Further, the investigations showed that the recovered ZnO nanorods could be reused up to five times. Some of

• the phospha-Michael adducts were converted to new phosphorylated heterocycles through intramolecular cyclization reactions. The phospha-Michael adduct 149 resulting from the three-component reaction of 6-methyl-3-formylchromone with malononitrile 145 or 2-cyanoacetamide 148 and diethyl phosphite is

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• Discussion Phenylhydrazine, 2-(ethoxymethylene)malononitrile, ethanol and benzaldehyde were selected as the model reactants. The influence of the reaction conditions was studied and the results are summarized in Table 1. No target product was afforded in the presence of an inorganic weak base or without a

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• [65]. Therefore, an employment of aliphatic carbonitriles which are less toxic and easier to handle (such as acetonitrile [66][67][68][69][70], benzyl cyanide [71][72][73][74][75][76], and malononitrile [77][78]) for the “CN” surrogates has been developed more recently [79]. We envisioned that the