Cyclic acyl amidines as unexpected C4-donors for fully substituted pyridine ring formation in the base mediated reaction with malononitrile

Tkachuk, Volodymyr A.; Merkulova, Vladyslava; Omelchenko, Irina V.; Arrault, Axelle; Hordiyenko, Olga V.

doi:10.1016/j.tetlet.2019.06.038

Cited by 5 publications

(6 citation statements)

References 44 publications

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“…It was formed, as we believe, by the sequential condensation of 1 with two malononitrile molecules and the subsequent heterocyclization of an intermediate 5 under the action of NaOMe (Scheme 2). This transformation can proceed similarly to that found by us in an earlier pyridine ring 6 formation by sodium methoxide-catalyzed ring-opening of 1H-isoindol-1-one (4), which was formed as it could be supposed by cyclization of the acid 3 32 (Scheme 2). The 1 H NMR spectrum of compound 6 was similar to that observed previously.…”

Section: -Cf 3 Cood (600 Mhz)supporting

confidence: 77%

“…The 1 H NMR spectrum of compound 6 was similar to that observed previously. 32 In a confirmation of the reaction route, a few days after separation of the acid 2f, small pale orange needle crystals of a substance, which was identified as 2-(1-amino-2,2-dicyanovinyl)benzoic acid (3) (17% yield) precipitated from the filtrate. That conclusion was made on the basis of the absence in the 1 H NMR spectrum of the characteristic signal of the 5′-pyrimidine proton at the region of  = 5-7, the presence of two closely spaced single-proton singlets at  = 8.62 and 8.72, which may correspond to non-equivalent protons of NH 2 group at a double bond, and a broad singleproton signal of the COOH group at  = 13.10.…”

Section: -Cf 3 Cood (600 Mhz)mentioning

confidence: 97%

“…The first ion was attributed to unreacted amidino acid 1, and the other two, given previous studies, probably corresponded to compounds 4 31,32 and 6 (Scheme 2). 32 Attempts to separate the mixture proved unsuccessful.…”

Section: Paper Synthesismentioning

confidence: 99%

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2-Carbamimidoylbenzoic Acid as a New Effective and Available Precursor for the Synthesis of Substituted 2-(Pyrimidin-2-yl)benzoic Acids

Tkachuk

Shishkanu

Tkachuk³

et al. 2020

Synthesis

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A new approach to the synthesis of 2-(pyrimidin-2-yl)benzoic acids based on the ring contraction of the 2-carbamimidoylbenzoic acid [(2-amidinobenzoic) acid] with 1,3-dicarbonyl compounds and their synthetic equivalents has been developed. The intramolecular condensation of the obtained acids with 1,3-dielectrophiles proceeds with the formation of the 4,6-dihydropyrimido[2,1-a]isoindole-4,6-dione system, the pyrrolidone ring of which is easily opened under the action of weak nucleophiles. The reaction of 2-amidinobenzoic acid with chromones, which have an aryloxy group at 3-position does not stop at the step of pyrimidine ring formation and undergoes further spontaneous cyclization into 2-(benzo[4,5]furo[3,2-d]pyrimidin-2-yl)benzoic acids.

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Section: -Cf 3 Cood (600 Mhz)supporting

confidence: 77%

Section: -Cf 3 Cood (600 Mhz)mentioning

confidence: 97%

See 1 more Smart Citation

2-Carbamimidoylbenzoic Acid as a New Effective and Available Precursor for the Synthesis of Substituted 2-(Pyrimidin-2-yl)benzoic Acids

Tkachuk

Shishkanu

Tkachuk³

et al. 2020

Synthesis

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“…Consequently, looking for effective and inaccessible anticancer agents with strong potency against cancerous cells remains a major task for scientists. Pyridines are among the most important biochemical scaffolds with broader uses in the medicinal and pharmaceutical industries as well as intermediates in heterocyclic preparations . Among pyridine derivatives, dicyanopyridines act as ‘privileged skeleton’ owing to their prospective uses for therapy .…”

Section: Background and Originality Contentmentioning

confidence: 99%

Design, Sonosynthesis, Quantum‐Chemical Calculations, and Evaluation of New Mono‐ and Bis‐pyridine Dicarbonitriles as Antiproliferative Agents

Arafa

Hussein

2020

Chin. J. Chem.

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of main observation and conclusion A highly efficient, simple, and clean single-step sonosynthetic procedure has been sophisticated for assembling new series of mono-and bis-pyridine dicarbonitriles from ketones, HCl, and tetracyanoethylene. The presented protocol is applicable for the preparation of a broad range of uniquely substituted pyridine dicarbonitriles and seems to be superior in comparison with other previously reported methods. The antiproliferative impact of the newly synthesized derivatives was screened towards three representative cancer cell lines (MCF-7, A549, and HCT116). Most of the evaluated derivatives showed a moderate to excellent anti-proliferative activity towards the selected cell lines. Of these, compounds 4h, 4k, 10, 12a, and 12b showed both potent anticancer activity (IC50<10 μM) and lower cytotoxic effect (IC50 > 58 μM) on non-tumorigenic cells (MCF-10A and NCM460), suggesting their promising potential to be lead molecules for future antitumor drug discovery. The structure-activity relationships have been also discussed. Moreover, quantum chemical studies based on Density Functional Theory (DFT) of the synthesized compounds were investigated and found to be consistent with the in vitro inhibitory activities. Results and DiscussionPreparation of 6-chloro-[2,2'-bipyridine]-4,5-dicarbonitrile (4a) by treatment of tetracyanoethylene (1, TCNE, 1.0 mmol), and 2-acetyl pyridine (2a, 1.0 mmol) with HCl (3.0 mL) was chosen as the template reaction (Scheme 1) under silent (70 o C) and ultra-502 www.cjc.wiley-vch.de

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“…1,3-diiminoisoindoline (DII), and 3-iminoisoindolinone were synthesized according to previously published procedures. [22][23][24] Semihemiporphyrazines 1-4 were synthesized according to the previously published procedure. [13] X-ray intensity data were measured on a Bruker CCD-based diffractometer with dual Cu/Mo ImuS microfocus optics (Cu Kα radiation, λ = 1.54178 Å, Mo Kα radiation, λ = 0.71073 Å).…”

Section: Methodsmentioning

confidence: 99%

Pyrazole and Indazole Semihemiporphyrazine Complexes of Rhenium Tricarbonyl: A Structure/Properties Study

et al. 2022

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The semihemiporphyrazines are a class of ligands comprised of a heterocycle ring and an isoindoline unit linked through a bridging nitrogen atom. These bidentate ligands can be altered in the exocyclic heteroatom position on the isoindoline and in the identity of the heterocycle. Herein, we present a series of Re(CO)3X (X=Cl, Br, py) complexes of indazole and pyrazole‐based semihemiporphyrazines. Changing the ligand and the axial position at the metal alters the character of the complexes, including the structure, tautomerization and charge of the chelate. Modifications to the semihemiporphyrazine also alter the electronic structure of the resultant Re(CO)3 complexed as demonstrated in their UV‐visible spectra. In addition to full characterization, we carried out density functional theory (DFT) and time‐dependent density functional theory (TDDFT) to interrogate the electronic structures of these compounds.

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Cyclic acyl amidines as unexpected C4-donors for fully substituted pyridine ring formation in the base mediated reaction with malononitrile

Cited by 5 publications

References 44 publications

2-Carbamimidoylbenzoic Acid as a New Effective and Available Precursor for the Synthesis of Substituted 2-(Pyrimidin-2-yl)benzoic Acids

2-Carbamimidoylbenzoic Acid as a New Effective and Available Precursor for the Synthesis of Substituted 2-(Pyrimidin-2-yl)benzoic Acids

Design, Sonosynthesis, Quantum‐Chemical Calculations, and Evaluation of New Mono‐ and Bis‐pyridine Dicarbonitriles as Antiproliferative Agents

Pyrazole and Indazole Semihemiporphyrazine Complexes of Rhenium Tricarbonyl: A Structure/Properties Study

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