Condensation Of Isatin Research Articles

Interconversions of 1,3-dipolar cycloaddition products of azomethine ylides and ylidenemalononitriles

New substituted spiropyrrole(zi)dynes were synthesized by the 1,3-dipolar cycloaddition reaction of ylidenemalononitriles and azomethine ylides generated in situ by condensation of isatin and α-amino acids (sarcosine, proline). The products′s features of the regio- and diastereochemical structure were elucidated depending on the nature of the amino acid and the reaction conditions. Based on data from the analysis of the spectra of cycloaddition products obtained under various conditions, as well as some additional experiments, a probable scheme for the formation of products was proposed, including retro-1,3-dipolar cycloaddition and the retro-Mannich reaction. Methods for the selective synthesis of isomeric spiropyrrolizidines were developed.

Magnetic Nanoparticles Based on DABCO as Catalysts in the Knoevenagel Reaction and Synthesis of Isatin-β-thiosemicarbazones

This work describes the route to prepare a novel core-shell catalyst based on 1,4-diazabicyclo[2,2,2]octane (DABCO) supported magnetic nanoparticles (MNPs). The morphology and composition of the obtained catalysts were characterized by Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), quantum design vibrating sample magnetometer (VSM) and scanning electron microscopy (SEM). These nanomaterials presented high performance as a basic catalyst for Knoevenagel condensation between malononitrile and aldehydes, leading to products with excellent yields (84-99%) and short reaction times (5-60 min). Furthermore, it was also efficient in the condensation of isatins with 4-phenylthiosemicarbazide, resulting in isatin-β-thiosemicarbazones with high yields (81-94%) and short times (60-180 min). It is worth mentioning that the catalyst was recovered and reused in these two kinds of reactions after six cycles without significant yield loss.

Development of New Azomethine Metal Chelates Derived from Isatin: DFT and Pharmaceutical Studies

Through the condensation of isatin (indoline-2, 3-dione) and aniline in a 1:1 ratio, a Schiff base ligand was synthesized and characterized via (1H-NMR, mass, IR, UV-Vis) spectra. Elemental analyses, spectroscopy (1H-NMR, mass, UV-Vis), magnetic susceptibility, molar conductivity, mass spectra, scanning electron microscope (SEM), and thermal analysis have all been used to characterize a series of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) metal complexes derived from the titled ligand. The metal-to-ligand ratio is 1:1, according to the analytical data. The Schiff base ligand displayed bidentate behavior with NO coordination sites when it bonded to metal ions, as seen by the IR spectra. The magnetic moment measurement and UV-Vis spectral investigation showed the octahedral geometry of the Cr(III), Fe(III), Co(II), Ni(II), and Zn(II) complexes, whereas they suggested the tetrahedral geometry of the Mn(II), Cu(II), and Cd(II) complexes. The thermal analysis study confirmed the presence of both hydrated and coordinated water molecules in all the compounds, except for the Mn(II) complex, and showed that the complexes decomposed in three or five decomposition steps leaving the corresponding metal oxide as a residue. The ligand and its metal complexes' antibacterial efficacy were evaluated. The findings showed that the metal complexes had stronger antibacterial properties than the ligand alone. The ligand and its metal complexes' anticancer properties were also investigated. A DFT investigation is also reported to gather information regarding the electronic features of the ligand and its metal complexes. Finally, drug-likeness and ADME characteristics were also calculated as parameters.

Iodine‐DMSO‐Promoted Oxygenation of Indoles: Synthesis of Isatin and Isoindigo

AbstractOxygenation/oxidative self‐coupling of indole are performed to obtain isatin and isoindigo in the absence of metal catalysts. Iodine‐DMSO is used to synthesize isatin whereas Iodine‐DMSO‐K2S2O8 combination is used for isoindigo synthesis directly from indole in a single step. Though several methods are known for isatin synthesis from indole, most of them use large quantity of oxidants or metal catalyzed. Moreover, the primary existing process for the synthesis of isoindigo is the condensation of isatin and oxindole in the presence of an acid catalyst. But this method provides isoindigo derivatives directly from indoles. A plausible mechanism is also proposed based on the various control experiments which indicate that both the reactions proceed via radical route. It is also observed that oxygen atoms of isatin and isoindigo come from water molecule and DMSO.

Synthesis of new 1H‐spiro[acridine‐9,3′‐indoline]‐1,2′(2H,10H)‐dione derivatives using aqueous ethanol as a reaction medium

AbstractOne‐pot three component synthesis of novel spiro[acridine‐9,3′‐indoline]‐1,2′(2H,10H)‐dione derivatives has been performed through the condensation of isatin, dimedone, and aniline under greener conditions. The remarkable features of this synthesis are use of ethanol:water mixture as a greener solvent and isolation of products by simple washing with water. The structures of the synthesized compounds have been well elucidated by various spectroscopic techniques.

Синтез полизамещенных спиропирролидинов с использованием 2-ацетилфурана, 2-ацетилтиофена и 2-ацетилпиррола

A series of novel spirooxindoles have been synthesized through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and sarcosine with the dipolarophile 3-phenyl-1-(heteroaryl -2-yl)prop-2-en-1- one, synthesized by the Knoevenagel reaction using 2-acetylfuran, 2-acetylpyrrole, 2-acetylthiophene and substituted benzaldehydes. These compounds are used for the first time as dipolarophiles. This method has the advantages of mild reaction conditions, high atom economy, excellent yields, and high regio- and stereo-selectivity. The reaction was carried out by mixing equimolar amounts of enone and isatin, as well as a slight excess of sarcosine in isopropyl alcohol when heated to 60–70°C. Among the enones with various heterocyclic substituents, it is most convenient to use compounds containing a pyrrole fragment as dipolarophiles, since the products are obtained in a short amount of time in good yields. The use of enones obtained from 2-acetylthiophene leads to an increase in the reaction time, and from 2-acetylfuran - to a significant resinification of the reaction mixture. The structures of the compounds obtained were proved using a combination of 1H, 13C NMR spectroscopy data, as well as two-dimensional NMR experiments of heteronuclear correlation, HSQC and HMBC. Based on the data obtained, a mechanism for the formation of products has been proposed.

Three-component one-pot synthesis of new spiro[indoline-pyrrolidine] derivatives mediated by 1,3-dipolar reaction and DFT analysis

A suitable one-pot sequential three-component synthesis of a series of new spiro[indoline-pyrrolidine] derivatives is described. Reactions proceeded through a 1,3-dipolar cycloaddition between azomethine ylides, generated in situ from the condensation of isatins with sarcosine, and trans-1,2-dibenzoylethylene as dipolarophile under conventional heating. This protocol provides a mild reaction condition with operational simplicity, affording high regioselectivity and stereoselectivity, enabling to assemble a complex structural entity in a single step in good to excellent yields. The regio- and stereochemical outcome of this cycloaddition reaction was ascertained by spectroscopic analysis. Also, DFT quantum chemical calculation was used to establish the geometries and electronic structures of the obtained compounds.

The Application of Encapsulated Trinuclear Cobalt Cluster Complex in Y Zeolite in the One-Pot Multi-Component Synthesis of Spiro Indoline Derivatives

A trinuclear cobalt cluster complex was prepared into the nanocages of dealuminated Y zeolite ([Co3(O)(CH3COO)6(py)3]-DAZY) and characterized by XRD, FT-IR, EDS, FE-SEM, AAS and BET-BJH analyses. The elemental content of Cobalt in [Co3(O)(CH3COO)6(py)3]-DAZY was estimated to be about 5.5 mg/g support on the basis of atomic absorption spectroscopy. The catalytic activity of [Co3(O)(CH3COO)6(py)3]-DAZY was evaluated in the synthesis of tri series of spiro indoline derivatives in a library synthesis via the condensation of isatins, malononitrile or ethylcyano acetate, and active methylene compounds (4-hydroxycoumarine, dimedone and pyrazoline-5-one). Corresponding products were obtained in good to excellent yields. Short reaction time, high yield of product, structural diversity of products, absence of organic solvents and the use of water as a green solvent, non-toxicity, stability and reusability of the catalyst are noteworthy advantages of the current work.

Synthesis and Some Reactions of 6H-Indolo[2,3-b]quinoxalines

6H-Indolo[2,3-b]quinoxalines were synthesized by condensation of isatin and 5-nitroisatin with o-phenylenediamine. The alkylation of the title compounds with dimethyl sulfate gave the corresponding quaternary salts which were converted to perchlorates and oxidized with potassium hexacyanoferrate(III) to previously unknown 5-methyl-6H-indolo[2,3-b]quinoxalin-3-one and its 9-nitro derivative. Treatment of 6H-indolo[2,3-b]quinoxalin-3-ones with dimethyl sulfate afforded 3-methoxyindoloquinoxalinium salts which were demethylated by the action of hydrobromic acid at 130–140°C. The structure of the isolated compounds was confirmed by IR and NMR spectra and elemental analyses.

Acetic acid catalysed solvent‐free synthesis of spiro‐isoxazolo[5,4‐b]pyridines/quinolines by mechano‐chemical grinding

AbstractA simple and efficient three‐component procedure has been developed for the synthesis of a series of spiro‐isoxazolo[5,4‐b]pyridines/quinolines by one‐pot condensation of isatins, 3‐methylisoxazol‐5‐amine and enolizable cyclic carbonyl compounds. The protocol has been accomplished under solvent‐free conditions by grinding the components at room temperature in presence of catalytic CH3COOH. The described process offers environmentally benign reaction conditions for the synthesis of pharmacologically important spirooxindole fused heterocycles with the advantages ofoperational simplicity, short reaction time and good to excellent yields of isolated pure product.

Isatin Derived Mixed Ligand Metal Complexes as Antimicrobial, Antioxidant Agents and Catalyst for Oxidation of Styrene

A novel series of mixed ligand transition metal complexes of Cu(II), Zn(II), Ni(II) and Co(II) have been synthesized from the Schiff base ligand, 3-(naphthalen-1-ylimino)indolin-2-one (achieved by the condensation of isatin and naphthylamine) and 1, 10-phenonthroline. The structural features were corroborated by means of elemental analyses, molar conductance, IR, UV-Vis, 1H NMR and mass spectral studies. The data displays that these complexes have the composition of [MLX] type where X = 1, 10-phenonthroline. The UV-Vis. and magnetic susceptibility data of the complexes suggest a square-planar geometry around the central metal ion. The IR spectral data of the ligand exhibits the presence of iminic group and its complexes manifest that the imine group of the Schiff base coordinate with the metal ion and decreased value of carbonyl group indicates which coordinate to the metal. The proton NMR spectrum of the ligand shows the presence of imine group. The mass spectral data also confirms the metal complexes as [MLX] type. Molar conductance values of the complexes have been found in the range of 5–14 ohm−1cm2mol−1, suggesting the non-electrolytic nature of the complexes. The antimicrobial study reveals that copper and cobalt complexes are better antimicrobial agents than the standard drug streptomycin and Nystatin. The copper and cobalt complexes exhibit remarkable antioxidant potential than the other complexes. The catalytic oxidation of styrene by H2O2 was carried out in acetonitrile in the presence of mixed ligand metal complex as catalyst. The result of the catalytic study reveals that the zinc complex effectively catalyses the oxidation of styrene.

Novel β‐amino Amide Organocatalysts for the Synthesis of Pharmaceutically Relevant Oxindoles

AbstractIn this work, a series of novel organocatalysts derived from unique unnatural β‐amino acid scaffold were synthesized and further developed to enhance the desired catalytic properties. Their evaluation was carried out in the asymmetric crossed‐aldol condensation of isatin and enolizable ketone donors. Following a systematic study of the reaction parameters including variations of additive, solvent, temperature, catalyst loading and substrate scope, (1R,2R)‐2‐amino‐N‐((R)‐1‐phenylethyl)cyclohexane carboxamide 9 proved particularly successful, affording the corresponding 3‐hydroxy‐3‐alkyl‐2‐oxindole in excellent yield (>99%) and distereoselectivity (>99% dr) with good enantioselective control (up to 52% ee) in the presence of p‐nitrophenol and EtOH in <24 h. An added benefit of this catalyst was its catalytic activity and selectivity at room temperature eliminating the requirement of reduced reaction temperatures. This scaffold, comprising of β‐amino amide, has not yet been applied in organocatalysis, thus, this is the first reported in this growing area. In mechanistic studies, direct infusion ESI‐MS proved a valuable tool forproposal of the catalytic cycle, confirming the formation of 2 key reaction intermediates.

Synthesis, Characterization and Study of Cytotoxicity, Antioxidant properties of Isatin based mixed Ligand Complexes

Present work deals with the study of two Schiff base ligands L1 (L1= Schiff base formed by the condensation of isatin and 2,4-dinitroaniline) and L2 (L2= Schiff base obtained by the condensation of isatin and p-amino toluene) and four mixed ligand complexes of the type [ML1L2X2] where M = Co(II), Ni(II), Cu(II) and Zn (II), X=Cl are synthesized. All the mixed ligand complexes have been analysed by modern techniques such as Elemental analysis, IR, UV-Visible, Conductivity measurements, Magnetic moment measurements, thermogravimetric analysis etc. octahedral geometry is assigned for all the four mixed ligand complexes. The ligands and the mixed ligand complexes are screened for cytotoxicity and antioxidant properties.

Synthesis of Spiro[oxindole-3,2′-pyrrolidine] Derivatives from Benzynes and Azomethine Ylides through 1,3-Dipolar Cycloaddition Reactions

A novel synthetic strategy employing benzyne and azomethine ylides for the construction of spiro[oxindole-3,2'-pyrrolidine] derivatives has been achieved in good yields. The ketimines obtained from the condensation of isatins with CF3CH2NH2 react with benzyne in the presence of weak bases such as TBAF or TBAT. This mild practical 1,3-dipolar cycloaddition provides an efficient route to access biologically active compounds.

The New Complexes of Selected Transition Metal Ions with a Ligand Formed by Condensation of Isatin with Amino Acid: Spectral, Thermal, and Magnetic Properties

The new complexes of 2-[(2-oxo-1,2-dihydroindol-3-ylidene)amino]butanoic acid, LH (where L = C12H11N2O3), with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) of general formulae MLCl·nH2O, for Co(II), Ni(II) and Cu(II), and ML2·H2O for Mn(II) and Zn(II), where n = 1, 2 depending on M(II) ions, are synthesized. The complexes crystallize in a monoclinic system, and upon heating in the air (293–1173 K) decompose in three steps forming eventually the corresponding oxides of the metals(II). In the course of this process the organic ligand decomposes releasing the molecules of H2O, CO2, NH3, CO, hydrocarbons, and additionally HCl for Co(II), Ni(II) and Cu(II) complexes. Magnetic moments of compounds are determined in the ranges of 76–303 and 2–300 K. All analyzed compounds, except that of Zn(II), demonstrate the paramagnetic properties with the ferro- and antiferromagnetic interactions between molecular centres.

An efficient catalyst-free approach for the synthesis of novel isoxazolo[5,4-b]pyridine derivatives via one-pot three-component reaction

A catalyst-free, one-pot, three-component condensation procedure for the synthesis of novel isoxazolo[5,4-b]pyridine derivatives has been reported by condensation of isatins, 3-methylisoxazol-5-amine, and cyclic enolizable carbonyl compounds in ethylene glycol at 80 °C. The structures of the synthesized compounds have been confirmed by spectral and X-ray studies. Crystal packing of one compound has also been reported. Less reaction time, easy work-up, and high yields are the important features of the present protocol.

Synthesis of Spirooxindoles through Cyclocondensation of Isatin and Cyclic 1,3‐Diones

A simple, clean, and efficient method for the synthesis of spirooxindole derivatives via condensation of isatin with enolizable cyclic β‐diketones has been developed. The use of water as a solvent allows avoiding the use of toxic organic solvents, which makes this reaction safe and environmentally friendly. The mechanism of the condensation reaction has been investigated using first‐principles‐based density functional theory calculations.

Synthesis and Characterization of New Bidentate Schiff Base Ligand Type (NO) Donor Atoms Derived from Isatin and 3-Amino Benzoic Acid and Its Complexes with Co(II), Cu(II), Cd(II) and Hg(II) Ions

New bidentate Schiff base ligand (L) namely [(Z)-3-(2-oxoindolin-3ylildeneamino)benzoic acid] type (NO) was prepared via condensation of isatin and 3-amino benzoic acid in ethanol as a solvent in existence of drops of (glac. CH3COOH). The new ligand (L) was characterized base on elemental microanalysis, FT-IR, UV-Vis, 1H-NMR spectra along with melting point. Ligand complexes in general formula [M(L)2Cl2]. H2O, where: MII = Co, Cu, Cd, and Hg; L= C15H10 N2O3 were synthesized and identified by FT-IR, UV-Vis, 1H-NMR (for Cd complex only) spectra, atomic absorption, chloride content along with molar conductivity and magnetic susceptibility. It was found that the ligand behaves as bidentate on complexation via (N) atom of imine group and (O) atom of carbonyl group of five member ring. The electronic spectral data and µeff values (Co, Cu) of the complexes exhibited octahedral geometry around CoII, CuII, CdII, HgII metal ions. The results of antibacterial activity showed that only Hg(II) complex has high activity (35 mm) for staphylococcus aureas.

One-pot synthesis of spirooxindole derivatives catalyzed by ZnFe2O as a magnetic nanoparticles

ZnFe2O4 as a novel nanoparticle was prepared and characterized using x-ray diffraction (XRD) analysis, energy dispersive x-ray (EDX), vibrating sample magnetometry (VSM), and fourier-transform infrared (FTIR) spectra. Then, it is used one-pot three-components synthesis of spirooxindole derivatives via condensation of isatin, malononitrile, and 1,3-dicarbonyl compounds (1,3-cyclohexanedione) under mild reaction conditions in water as a green solvent. The present methodology offers several advantages, including ease of the preparation and handling of the catalyst, simple and easy work-up, short reaction times, high yields of the products and recyclability of the catalyst.

Regio- and stereoselective synthesis of dispirooxindole-pyrrolocarbazole hybrids via 1,3-dipolar cycloaddition reactions: Cytotoxic activity and SAR studies

A library of novel dispiro compounds containing oxindole-pyrrolo-carbazole hybrid frame works has been synthesized in a fully regio- and stereoselective fashion by the three-component 1,3-dipolar cycloaddition of azomethineylides generated in situ from the condensation of isatins and benzylamine with 2-arylidene/heteroarylidene-2,3,4,9-tetrahydro-1H-carbazole-1-one. The structures of the compounds were established by FT-IR, 1H NMR, 13C NMR, X-ray diffraction and elemental analysis. The synthesized dispiro heterocycles have been screened for in vitro cytotoxic activity by MTT assay and displayed enviable growth inhibition on both the cancer cell lines i.e. breast cancer cell line MCF-7 and lung cancer cell line A-549. Morphological changes and apoptosis induction have been studied by inverted light microscopic, fluorescent microscopic techniques and by flow cytometry analyses. The preliminary structure activity relationships were also carried out. Data indicated that among dispiro-carbazole compounds,6-chloro-4'-(thiophen-2-yl)-5′-phenyl-3,4-dihydrodispiro[carbazole-2,3′-pyrrolo-2′,3″-indole]-9(H)-1,2″-dione 7e could be exploited as a significant therapeutic drug against breast cancer as well as lung cancer cell proliferation.