Reaction Of Isatins Research Articles

One‐pot synthesis of spiro‐acridine/indoline and indoline derivatives using (MWCNTs)‐COOH/La2O3 hybrid as an effective catalyst

AbstractSpiro‐acridine/indoline and indoline derivatives were synthesized by the three‐component reaction of isatin, dimedone, and amines or amino acids in the presence of acid‐functionalized multiwalled carbon nanotubes/La2O3 (MWCNTs)‐COOH/La2O3 hybrid (5 mol%) as a highly efficient catalyst in ethanol. The assigned structure was further established by CHN analysis, NMR, and FTIR spectra. (MWCNTs)‐COOH/La2O3 was fabricated by the reaction of functionalized (MWCNTs)‐COOH and La(NO3)3.6H2O in acetic acid. Synthesis of La2O3 nanoparticles and their conjugation on the surface of MWCNT have been confirmed by FTIR, scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, and energy‐dispersive X‐ray spectroscopy.

Aqueous NH3-mediated syntheses of 2-styrylquinoline-4-carboxamides by domino ring opening cyclization strategy

A straightforward and efficient protocol for the synthesis of medicinally relevant 2-styrylquinoline-4-carboxamide has been developed by aqueous ammonia-mediated domino ring-opening and cyclization strategy of 3-hydroxyoxindole. The starting precursors 3-hydroxyoxindoles were easily prepared through organocatalytic “on water” reaction of isatin and benzalacetone in high yields. The wide substrate scope with operationally simple experimental procedures provides an opportunity to create library of 2-styrylquinoline-4-carboxamide derivatives.

Enhancement of the biochemical activity of some market antibiotics by chemical modification: Synthesis, characterization, and biochemical evaluation

AbstractThe reaction of isatin with the Ampicillin gave the new compound: (6R)‐3,3‐dimethyl‐7‐oxo‐6‐(2‐(([E]‐2‐oxoindolin‐3‐ylidene)amino)‐2‐phenylacetamido)‐4‐thia‐1‐azabicyclo[3.2.0]hept ‐ane‐2‐carboxylic acid (HAI). The new complexes derived from HAI and Co(II), Ni(II), Cu(II), Eu(III), and Gd(III) were obtained in pure form. The obtained compounds were characterized by elemental analysis, FTIR, UV–Vis, Fluorescence, 1HNMR, Mass spectra, DTA, TGA, Magnetic susceptibility, X‐ray, AAS, and the conductivity of 0.001 M in DMSO. The obtained data indicated the formation of the target complexes: [Co(HAI)(H2O)(NO3)]NO3.4H2O, [Ni(AI)(H2O)2]Cl.2H2O, [Cu(AI)]Cl.H2O, [Eu(AI)(H2O)Cl]Cl.5H2O and [Gd(AI)(H2O)(NO3)]NO3.3H2O. The ligation sites were predicted from the guide of the FTIR and thermal analysis meanwhile the stereochemistry was proved by the UV–Vis and magnetic moment. Co(II) and Ni(II) gave an octahedral structure while Cu(II) gave a square planar form. Molecular modeling, molecular mechanics, and DFT calculations were carried out for the synthesized compounds. The active lone pair and surface properties were obtained and discussed in the silico level. The x‐ray analysis indicates the nanoparticle behavior of the Cu‐AI complex with a monoclinic structure. The interactions of the synthesized complexes with FM‐DNA moiety were investigated through spectrometric titration (UV–vis. spectra) and by using fluorescence spectroscopy. The modes and binding affinities were evaluated and discussed using Benesi–Hildebrand method. Antimicrobial activities of the synthesized compounds have been screened using the disc diffusion method. HAI and Cu‐AI gave activity exceeded the Ampicillin. The docking work was carried using the targeting protein of Escherichia coli FabH (PDB code: 1HNJ). The obtained binding energy was compared and discussed in terms of the in vitro studies.

Review of Chemical, Pharmacological, Biological Activities of Isatin and Its Derivatives – Part-2 (2002 To 2020)

: Isatin is a naturally occurring substance identified in humans, animals, plants and coal tar. Isatin derivatives are reported to possess a wide range of activites. This review is in continuation of “Part-1 (1877-2002)” review published by our team. This review encompasses the most signigicant reports published during 2002 to 2020 on the biological & pharmacological activites of isatin and its derivatives. The review includes the various synthetic reactions of isatin and activites reported. The pharmacological and biological activites reported were antimicrobial, antineoplastic & related activities; analgesic, anti-inflammatory, anticonvulsant, antioxidant, activity against veterinary pathogen, effects on cardiac & vascular smooth muscles; transthyretin fibrillogenesis inhibitor and antiglycation activity of isatin compounds.

Krapcho Dealkoxycarbonylation Strategy of Ethyl Cyanoacetate for the Synthesis of 3-Hydroxy-3-cyanomethyl-2-oxindoles and 3,3′-Dicyanomethyl-2-oxindoles in a Reaction with Isatin

A new strategy for the synthesis of 3-hydroxy-3-cyanomethyl-2-oxindoles and 3,3′-dicyanomethyl-2-oxindoles in a reaction of isatin with ethyl cyanoacetate by Krapcho dealkoxycarbonylation reaction in aqueous media is demonstrated. The reaction provides an easy access to synthetically and medicinally valuable oxindole alkylnitriles in good to very good yields. Wider substrate scope and operationally simple experimental procedures are highlighted features of the developed protocol. Based on control experiments, a plausible mechanism of reaction and synergistic effect of water is also rationalized.

A quick and regioselective access of spirooxindole‐oxazoline by reaction of isatin and isocyanoacetate “on water”

AbstractA greener, rapid and regioselective “on water” synthesis of spirooxindole‐oxazoline by the reaction of isatin and isocyanoacetate at room temperature is described. The developed protocol has the advantage of being atom‐economical, eco‐friendly, and benign reaction conditions. Broader substrate scope, experimentally simple procedures, and easy purification of products with high yield further make this method attractive. The synthesized compounds have been fully characterized with spectral analysis.

Efficient Multicomponent Synthesis of Spirooxindole Derivatives Catalyzed by Copper Triflate

A simple and efficient method for the synthesis of spirooxindole derivatives via a three-component reaction of isatin, 5-aminopyrazole, and 1,3-dicarbonylcompounds (or β-​oxo-benzenepropanenitril​e) catalyzed by copper triflate in ethanol is described. The advantages of this method include high efficiency, mild reaction conditions, recoverable catalyst, and environmentally benign conditions.

Three‐component electrosynthesis of spirooxindole‐pyran derivatives through a simple and efficient method

AbstractAn eco‐friendly and highly efficient process has been applied to synthesize spirooxindole‐pyran derivatives in a one‐pot container via a three‐component reaction of isatins, malononitrile, and an enolizable CH‐activated compound of diethyl 3‐oxopentanedioate under constant current in n‐propanol under a temperature of 50°C. The proposed method shows high yields through green reaction conditions along with other significant advantages. Among which stand out applying clean electrons as a reproducible source of energy instead of an organic catalyst, using an environmentally friendly solvent for instance propanol, a multicomponent reaction with mild condition happening in a one‐pot container, and no chromatographic separation.

A survey on the characterization and biological activity of isatin derivatives

The derivatives of isatin have already been known to display a variety of biological activities. Therefore, the studies on their activity and its relation to structure have recently become a popular subject for investigation. The examined compounds were synthesized by the reaction of isatin and substituted primary amines and characterized by spectroscopic methods. The investigation of the antimicrobial and antioxidative activity of the synthesized compounds was performed by broth microdilution method. As for the characterization of the investigated isatin based Schiff bases, the linear solvation energy relationships (LSER) were used to analyze the solvent influence on the UV absorption maxima shifts (?max), using the well known Kamlet?Taft model and taking geometrical isomers into consideration when possible. Linear free energy relationships (LFER) were used to analyze substituent effect on pKa, as well as NMR chemical shifts and ?max values. The antimicrobial activity and characterization were related using both experimental and theoretical methods.

Regioselective, one-pot, multi-component, green synthesis of substituted benzo[c]pyrazolo[2,7]naphthyridines.

An efficient and environmentally benign synthetic protocol has been developed for the synthesis of benzo[c]pyrazolo[2,7]naphthyridine derivatives through regioselective multi-component “on-water” reaction of isatin, malononitrile and 3-aminopyrazole. The Knoevenagel condensation of isatin with malononitrile resulted in the formation of arylidene, which subsequently underwent Michael addition with 3-aminopyrazole followed by basic hydrolysis, cyclization, decarboxylation and aromatization to give the target naphthyridines in good to excellent yields. The one-pot multi-component protocol was also employed to obtain the said naphthyridines in a lower yield (10–15%) than obtained by basic hydrolysis of spiro-intermediates. The present study shows attractive features such as the use of water as a green solvent, short reaction time, reduced waste products and transition metal free C–C and C–N bond formation. The structures of the synthesized derivatives were established through FTIR, 1H-NMR, 13C-NMR spectroscopy and ESI-mass spectrometry.

CsF promoted rapid synthesis of spirooxindole‐pyran annulated heterocycles at room temperature in ethanol

AbstractA newer, versatile, and straightforward synthetic strategy for the construction of functionalized spirooxindole‐pyran annulated heterocycles is described. The procedure is based on CsF‐promoted rapid tandem Knoevenagel‐Michael‐Cyclocondensation reaction of isatin, malononitrile, and 4‐hydroxycoumarin/barbituric acids/pyrazolone at room temperature in ethanol. This methodology has various advantages like easy operational, excellent yields within short reaction time (3‐25 min), and simple isolation of products. The CsF has a dual role as a base and carbonyl activator.

Silica-Coated Magnetic-Nanoparticle-Supported DABCO-Derived Acidic Ionic Liquid for the Efficient Synthesis of Bioactive 3,3-Di(indolyl)indolin-2-ones.

In this work, biologically significant 3,3-di(indolyl)indolin-2-ones have been synthesized using a silica-coated magnetic-nanoparticle-supported 1,4-diazabicyclo[2.2.2]octane (DABCO)-derived and acid-functionalized ionic liquid as the catalytic entity. The fabricated nanocomposite catalyzes the pseudo-three-component reaction of isatins and indoles explicitly via hydrogen-bonding interactions between substrates and the catalyst. The nanocatalytic system utilizes water as the green reaction medium to obtain a library of indolinones in good to excellent yields under mild reaction conditions. Besides, the catalyst could be easily recovered from the reaction mixture through simple external magnetic forces, which enables excellent recyclability of the catalyst for successive runs without appreciable loss in catalytic activity. Hence, the outcomes of the present methodology make the nanocatalyst a potential candidate for the development of green and sustainable chemical processes.

Isatin Aldazines Synthesis using A Proton Exchanged Algerian Montmorillonite Clay as Acid Eco-friendly Catalyst

An efficient and easy procedure is developed for the synthesis of isatin aldazines or bis-Schiff bases of isatin, catalyzed by a proton exchanged Algerian montmorillonite clay (MMT-H+) as green catalyst. The products were obtained in two catalyzed steps under conventional heating in ethanol. Isatin-3-hydrazone obtained from the reaction of isatin with hydrazine monohydrate reacts in the second step with the appropriate aromatic aldehydes to give the desired products in good yields. The main advantages of using this protonated solid non-toxic catalyst in this synthesis are its availability and low cost, the simplicity of its use, the recycling possibilities without significant loss of its catalytic activity and its environmentally benign process.

Approaches towards 3‐Substituted‐3‐hydroxyoxindole and Spirooxindole‐Pyran Derivatives in a Reaction of Isatin with Acetylacetone in Aqueous Media

AbstractThe synthetic utility of C1 and C3 nucleophilic behavior of acetylacetone in a reaction with isatin for two distinct pharmaceutically relevant scaffolds 3‐substituted 3‐hydroxyoxindole and spirooxindole‐pyran in water is presented. The protocol offers environmentally benign conditions, wide substrate scope, and good to the very good chemical yield of products. The developed methodology has the potential to generate a library of useful synthetic compounds that are of pharmaceutical interest. A plausible mechanism for the formation of products based on the outcome of the reaction is also rationalized.

Synthesis, Characterization and in vitro Antibacterial evaluation of New Oxindoles and Spiro-Oxindoles Derivatives

Arylidenes oxindole 3 and 5 were synthesized via the reactions of isatin 1 with malononitrile dimmer 2 and 5-amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile 4. Compound 3 react by Michael addition with malononitrile, ethyl 2-cyanoacetate and acetyl acetone to give 6'-amino-2'-(dicyanomethylene)-2-oxo-2',3'-dihydro-1'H-spiro[indoline-3,4'-pyridine]-3',5'-dicarbonitrile 6a, 2'-(dicyanomethylene) 2,6'-dioxospiro[indoline-3,4'-piperidine]-3',5'-dicarbonitrile 6b and 2-(5'-acetyl-3'-cyano-6'-methyl-2-oxo-1'H-spiro[indoline-3,4'-pyridin]-2'(3'H) ylidene) malononitrile 7, respectively. compound 3 also, reacted with dimethylformamide dimethyl acetal to give N,N-dimethyl-N'-(1,1,3-tricyano-3-((Z)-2-oxoindolin-3-ylidene)prop-1-en-2-yl)formimidamide 7 which cyclized by ammonium acetate to give 4-amino-6-(cyano(2-oxoindolin-3-ylidene)methyl)pyrimidine-5-carbonitrile 8. Compound 5 reacted with dimedone 10 and acetyl acetone to give 3-(cyano(2-oxoindolin-3-ylidene)methyl)-5-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino)-1H-pyrazole-4-carbonitrile 11 and 2-(cyano(2-oxoindolin-3-ylidene)methyl)-5,7dimethylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 12. Moreover, compound 3 and 5 reacted with hydrazine to give 3,3'-(hydrazine-1,2-diylidene)bis(indolin-2-one) 15. The antibacterial activities of the synthesized compounds were evaluated.

Isatins 3-C annulation vs ring-opening: Two different pathways for synthesis of spiro compounds via multicomponent reactions

An efficient synthesis of spiro compounds via two different pathways from the reactions of isatins, 3-phenylisoxazol-5(4H)-one (3-ethylisoxazol-5(4H)-one), and pyrazol-5-amine (6-aminopyrimidine-2,4(1H,3H)-dione) were reported. The catalyst Amberlyst-15 could be easy recycled and reused for many time without any appreciable loss in catalytic activity. The new type spiro compounds were gained through the ring-opening of isatins process. The structures of spiro[indoline-3,4′-isoxazolo[5,4-b]pyrazolo[4,3-e]pyridin]-2-one, spiro[isoxazolo[5,4-b]quino line-4,5′-pyrrolo[2,3-d]pyrimidine]-2′,4′,6′(1′H,3′H,7′H)-trione, and spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2,6′(5′H)-dione were successfully confirmed by 1H NMR, 13C NMR, HRMS, and X-ray crystal diffraction analysis.

Regioselective Synthesis of Carbazole‐Grafted Dispirothiapyrrolizine Derivatives via 1,3‐Dipolar Cycloaddition Strategy

AbstractA library of dispirooxindole‐thiapyrrolizine derivatives have been prepared via 1,3‐dipolar cycloaddition of azomethine ylide, generated in situ from the reaction of isatin and thiaproline with a series of 2‐arylidene/heteroarylidene‐2,3,4,9‐tetrahydrocarbazol‐1‐ones. Moderate to good yields were obtained for these reactions and also for spiro compounds of acenaphthenequinone obtained using the same optimized reaction condition. The structures of the spiro compounds were established by FTIR, 1H NMR, 13C NMR and elemental analysis. The regio‐ and stereo‐chemistry of the spiranic adducts were ascertained by single crystal X‐ray diffraction studies.

Imidazole mediated synthesis of spirooxindoles in water using isatin as a privileged scaffold

This work describes the synthesis of complex small molecules spirooxindoles using imidazole as an efficient organocatalyst. The three components coupling reactions of isatin, malononitrile and enolizable 4-hydroxycoumarin were performed in water as a green solvent. The reaction is done with imidazole an amphoteric organocatalyst to construct spiro-molecules in high yields. The significant features of this protocol are neutral reaction condition, readily available low cost catalyst, metal free, strong acid/base free, and reusable reaction medium with no column chromatography separation. This methodology is useful for the easy access of structurally complex, highly functionalized spirooxindole molecules with important medicinal chemistry applications.

An Efficient Five‐Component Reaction for the Synthesis of 4,4′‐((2‐Oxoindoline‐3,3‐diyl)bis(methylene))bis(2‐aryl‐1H‐pyrrolo[3,4‐c]quinoline‐1,3(2H)‐dione) Derivatives

An efficient cascade process five‐component reaction of isatins and 3‐oxo‐N‐arylbutanamide for the synthesis of 4,4′‐((2‐oxoindoline‐3,3‐diyl)bis(methylene))bis(2‐aryl‐1H‐pyrrolo[3,4‐c]quinoline‐1,3(2H)‐dione) derivatives was reported under mild condition. The advantages of this strategy are easy to obtain raw materials, convenient one‐pot procedure, and simple operation.

Tin powder promoted synthesis of trifluoroethylamine‐containing 3,3′‐disubstituted oxindoles

An efficient and facile approach for the construction of trifluoroethylamine‐containing 3,3′‐disubstituted oxindoles or 3‐spirooxindoles is developed through the reaction of isatins, 2,2,2‐trifluoroethylamine hydrochloride and allyl bromides or 2‐(bromomethyl)acrylic ester mediated by tin powder. This method uses simple and commercially available 2,2,2‐trifluoroethylamine hydrochloride as a trifluoroethylamine building block and avoids the use of toxic allylstannanes.