Environmental Friendly Synthesis of Novel Isatin Ketal and Isatin Schiff Base Derivatives Using Michael Addition Reaction under Solvent‐Free Conditions

An efficient and simple procedure for the synthesis of novel isatin derivatives is described. Michael addition of aniline Schiff bases of isatin or p‐toluidine Schiff bases of isatin to fumaric esters affords the Michael adduct compounds in good to high yields in the presence of K₂CO₃ and tetrabutylammonium bromide (TBAB) under solvent‐free conditions. Repeating of this reaction about spiro[1,3‐dioxolane‐2,3′‐indol]‐2′(1′H)‐one, as a Michael donor, in the presence of 1,4‐diazabicyclo[2.2.2]octane (DABCO) gives Michael adducts in remarkable yields under the same conditions.     

Synthesis and study of 2-(1-pyrazolyl)pyrimidine derivatives

Alkyl derivatives of 2-(1-pyrazolyl)-4(3H)-pyrimidinone were synthesized and converted to 4-chloro-, 4-arylamino-, and 4-hydrazino-2-(1-pyrazolyl)pyrimidines. The corresponding hydrazones were obtained by reaction of 5-ethyl-2-hydrazino-6-methyl-2-(4-ethyl-3,5-di-n-propylpyrazolyl) pyrimidine with isatin and salicylaldehyde. The UV and IR spectra of the synthesized compounds were studied. It was established that the hydrazones contain intra-molecular hydrogen bonds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1255–1257, September, 1977.     

Me3SiCl and Et3SiI‐promoted one‐pot synthesis of 1,4‐dihydropyridine derivatives

An efficient synthesis of 1,4‐dihydropyridine derivatives has been achieved by the one‐pot cyclocondensation reaction of methyl 3‐aminocrotonate and a range of aldehydes in the presence of chlorotrimethylsilane as a promoter under solvent‐free conditions. The cyclocondenstion reaction requires a very short time and takes place in good to excellent yields. Furthermore iodotriethylsilane, generated in situ by the reaction of triethylsilane and methyl iodide in the presence of palladium chloride, has been investigated for the synthesis of 1,4‐dihydropyridine derivatives. This facile and efficient method affords high yields for the preparation of 1,4‐dihydropyridines at room temperature and short reaction times. Copyright © 2009 John Wiley & Sons, Ltd.     

An Environmental Friendly Approach for the Synthesis of Spiro[indoline‐3′,2‐quinazoline]2′,4(3H)‐dione Using 1‐Methylimidazolium Hydrogen Sulfate,as Reusable Catalyst

A facile and environmentally benign procedure for the synthesis of 3‐aryl‐1H‐spiro[indoline‐3′,2‐quin‐azoline]2′,4(3H)‐dione from isatoic anhydride, aromatic amines and isatin derivatives in Brønsted acidic ionic liquid, 1‐methylimidazolium hydrogen sulfate, was reported. The ability to reuse the ionic liquid, the high yield, short reaction time and ease of purification are the important features of this process.     

One‐pot three‐component synthesis of novel 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carboxylic acid derivatives

A simple and easy synthesis of 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carboxylic acid ( 3 ) has been successfully developed through a one‐pot three‐component condensation reaction of (2‐amino‐phenyl)‐oxo‐acetic acid sodium salt ( 1 ) obtained from the hydrolysis of isatin with ammonium acetate and 3‐nitrobenzaldehyde. Some novel quinazoline‐ester derivatives 4‐7 were then obtained by the reaction between the new compound 3 and various alcohols. Then, quinazoline‐amide derivatives 10‐14 were synthesized from the reaction of various amines and 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carbonyl chloride ( 8 ), obtained by the reaction of compound 3 with SOCl₂. Finally, some novel quinazoline‐azo derivatives 17‐19 were synthesized by the coupling reaction between β‐dicarbonyl compounds and the novel amino‐quinazoline derivative compound 15 , obtained by reduction of nitro‐quinazoline derivative compound 11 . Thus, a new series of quinazoline‐4‐carboxylic acid, ester, amide, and azo derivatives was synthesized and fully characterized by ¹H NMR, ¹³C NMR, IR, and mass spectrometry analysis.     

Cyclization of thiohydrazonate esters and azo‐hydrazone tautomerism of 2‐arylhydrazono‐3‐oxo‐1,4‐benzothiazines

Reaction of ethyl arylhydrazonochloroacetates ( 1 ) with 2‐aminothiophenol ( 2 ) in ethanol in the presence of triethylamine yielded the respective ethyl thiohydrazonate esters ( 3 ). Similarly, methyl arylhydrazonochloroacetates ( 6 ) gave the corresponding methyl thiohydrazonate esters ( 7 ). Treatment of both 3 and 7 with hydrogen chloride in ethanol afforded the respective 1,4‐benzothiazine derivatives 4 . Identical products ( 4 ) were obtained by refluxing 1 or 6 in ethanol in the presence of triethylamine. The structure of 4 was confirmed by their alternate synthesis starting with diethyl chloromalonate in ethanol in the presence of triethylamine which yielded the intermediate 1,4‐benzothiazine derivatives 8 . The subsequent coupling of 8 with diazotized anilines in ethanol in the presence of potassium hydroxide afforded 4 .     

Synthesis of 3-aryl-3-hydroxypyrrolidin-2-ones and 2-benzyl-9b-hydroxy-3,3a,5,9b-tetrahydro-2H-pyrrolo[3,4-c]quinoline-1,4-dione derivatives from the Baylis-Hillman adducts of isatins

We prepared some 3-aryl-3-hydroxypyrrolidin-2-ones and tricyclic 2-benzyl-9b-hydroxy-3,3a,5,9b-tetrahydro-2H-pyrrolo[3,4-c]quinoline-1,4-diones starting from the Baylis-Hillman adducts of isatin derivatives.     

Synthesis and Antimicrobial Activity of Novel Heterocycles Utilizing 3‐(1,4‐Dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile as Precursors

The reaction of 3‐(1,4‐dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile 1 and salicyladehyde furnished coumarin derivatives 4 and 5 . Coupling reaction of 1 with aryl diazonium chlorides and benzene‐1,4‐bis (diazonium) chloride gave the corresponding hydrazones 6a , b and bishydrazone 9 , respectively. Hydrazones 6 underwent intramolecular cyclization upon treating with hydrazine hydrate to give 3‐aminopyrazoles 7 . Pyranyl phthalazine 13 was prepared from the reaction of 1 with ethyl 2‐cyano‐3‐ethoxyacrylate 10 . Enaminonitrile 14 was reacted with hydrazine hydrate/phenylhydrazine and hydroxylamine to afford the corresponding pyrazoles 16 and oxime 17 . The antimicrobial evaluation revealed pyrazole derivatives 7a , b and 16a , b displayed a broad spectrum activity against most strains. 3‐Aminopyrazole derivative 7b showed potent antibacterial activity against all tested microorganisms.     

Efficient one-pot synthesis of spiro[indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine]dione via three-component reaction

An efficient one-pot synthesis of spiro[indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine] dione derivatives via three-component reaction of 5-amino-3-methylpyrazole, isatin, and thioacid is described. This new protocol produces novel heptacyclic spirooxindole derivatives in good yields in comparison to conventional pentacyclic compounds. This method proceeds through a 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindoline intermediate (Baylis-Hillman type adduct), unlike 3-indolylimine (the intermediate like Shiff-Bases) as in conventional methods. The structure of one representative compound has been confirmed by X-ray diffraction analysis.     

A Facile One‐Pot Synthesis of Substituted Quinolines via New Multicomponent Reaction

An efficient synthesis of quinoline derivatives is described via the reaction between ethyl chloropyruvate or alkyl 4‐chloroacetoacetate and activated acetylenic compounds in the presence of nucleophilic form of isatin in water as the solvent. Nucleophilic form of isatin is produced from the reaction of isatin and triethylamin.     

Simple synthetic routes to 5-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-1H-indole-2,3-diones and their Derivatives

Two different synthetic routes to 5-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-1H-indole-2,3-diones are described. The reaction sequences represent a facile entry into these series of isatin derivatives.     

Intramolecular Schmidt reaction of tert-butyl 3-(3-azidopropyl)-4-oxopiperidine-1-carboxylate as a synthetic route to saturated fused aza heterocycles

Treatment of the title compound with trifluoroacetic acid induced intramolecular Schmidt reaction with formation of a saturated fused heterocyclic system, tert-butyl 5-oxo-2,3,4,5,7,8,9,9a-octahydro-1H-pyrrolo[1,2-a][1,4]-diazepine-2-carboxylate. The latter was reduced with lithium tetrahydridoaluminate, and subsequent treatment with hydrogen chloride in dioxane gave 2,3,4,5,7,8,9,9a-octahydro-1H-pyrrolo[1,2-a][1,4]-diazepine dihydrochloride which is a promising intermediate product for the synthesis of N-substituted diazepines with a fused pyrrole ring.     

A facile synthetic approach to novel spiro-oxindoles/acenaphthylen-1-ones containing benzo[1,4]thiazin-3-one ring via 1,3-dipolar cycloaddition

A series of spiro-oxindole derivatives containing spirobenzo[1,4]thiazin-3-one ring were synthesized regioselectively via a multicomponent 1,3-dipolar cycloaddition of isatin, 2-(4-methyl-benzylidene)-4H-benzo[1,4]thiazin-3-one and sarcosine or l-proline in toluene under reflux condition. Also spiro-acenaphthylen-1-ones containing spirobenzo[1,4]thiazin-3-one ring have been synthesized using 2-(4-methyl-benzylidene)-4H-benzo[1,4]thiazin-3-one as dipolarophile. The methodology affords high yields of products in short reaction time.     

Synthesis of substituted tryptanthrins via oxidation of isatin and its derivatives

Oxidation of isatin and its 5-substituted analogs with potassium permanganate in anhydrous acetonitrile gave indolo[2,1-b]quinazoline-6,12-dione (tryptanthrin) and its 2,8-dimethyl-, 2,8-dibromo-, and 2,8-diiodo derivatives. Oxidative coupling of 5,7-dichloroisatin with isatin under analogous conditions afforded 2,4-dichloroindolo[2,1-b]quinazoline-6,12-dione, while 1,4-dichloroindolo[2,1-b]quinazoline-6,12-dione and 1,4-dichloro-8-methylindolo[2,1-b]quinazoline-6,12-dione were obtained by oxidative coupling of 4,7-dichloroisatin with isatin and 5-methylisatin, respectively.     

Asymmetric Triple Relay Catalysis: Enantioselective Synthesis of Spirocyclic Indolines through a One‐Pot Process Featuring an Asymmetric 6π Electrocyclization

A rare example of a one‐pot process that involves asymmetric triple relay catalysis is reported. The key step is an asymmetric [1,5] electrocyclic reaction of functionalized ketimines. The substrates for this process were obtained in situ in a two‐step process that involved the hydrogenation of nitroarenes with a Pd/C catalyst to yield aryl amines and their subsequent coupling with isatin derivatives in a Brønsted acid catalyzed ketimine formation reaction. The electrocyclization was catalyzed by a bifunctional chiral Brønsted base/hydrogen bond donor catalyst. The one‐pot process gave the desired products in good yields and with excellent enantioselectivity.     

Novel four-component route to the synthesis of spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives

An effective route to spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives is described. This involves reaction of isatin, 1-phenyl-2-(1,1,1-triphenyl-λ⁵-phosphanylidene)-1-ethanone, and benzylamine derivatives or aliphatic amines in the presence of alkyl acetoacetate (1,3-dicarbonyl compounds) in dry methanol under reflux conditions. The reactive 1:1 enaminone, which is obtained from the addition of the amine to 1,3-dicarbonyl compound, adds to the α,β-unsaturated ketone, which is formed from the reaction of isatin and 1-phenyl-2-(1,1,1-triphenyl-λ⁵-phosphanylidene)-1-ethanone, to produce the alkyl 1′-benzyl-2′-methyl-2-oxo-6′-phenyl-1′H-spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives in excellent yields.     

Synthesis,antiviral and antimicrobial screening of some new 2-oxoindoline derivatives

New 3-(2-(5-(aryldiazenyl)-4-methylthiazol-2-yl)hydrazono)indolin-2-ones were prepared by the reaction of isatin β-thiosemicarbazone with different hydrazonoyl chlorides. Imide derivatives were prepared by the reaction of isatin hydrazone with various anhydrides, and a series of new sulfonimides was also synthesized. All new compounds were tested for their biological activities.     

Improved Syntheses of Halofuranose Derivatives with the Desired α-Configuration

Chlorination of ribofuranose or 2-deoxyribofuranose derivatives was carried out in a 1,4-dioxane solution of hydrogen chloride. This improved procedure allowed the syntheses of 1-chloro-α-D -ribofuranose and 1-chloro-2-deoxy-α-D -ribofuranose derivatives and offered ease of handling, high yield, and the stereo-controlled α-configuration at C-I.     

Nanomagnetically modified thioglycolic acid (γ‐Fe2O3@SiO2‐SCH2CO2H): Efficient and reusable green catalyst for the one‐pot domino synthesis of spiro[benzo[a]benzo[6,7]chromeno[2,3‐c]phenazine] and benzo[a]benzo[6,7]chromeno[2,3‐c]phenazines

Superparamagnetic nanoparticles of modified thioglycolic acid (γ‐Fe₂O₃@SiO₂‐SCH₂CO₂H) represent a new, efficient and green catalyst for the one‐pot synthesis of novel spiro[benzo[a ]benzo[6,7]chromeno[2,3‐c ]phenazine] derivatives via domino Knoevenagel–Michael–cyclization reaction of 2‐hydroxynaphthalene‐1,4‐dione, benzene‐1,2‐diamines, ninhydrin and isatin. This novel magnetic organocatalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least six times without significant loss in its activity. The catalyst was fully characterized using various techniques. This procedure was also applied successfully for the synthesis of benzo[a ]benzo[6,7]chromeno[2,3‐c ]phenazines.     

Chemistry of 2-hydroxy-2-(dimethylaminomethyl)-1,1,4,4-tetramethyl-1,4-diazonia-2,5-diboratacyclohexane

Reactions at OH and NMe₂ functionalities of 2-hydroxy-2-(dimethylaminomethyl)-1,1,4,4-tetramethyl-1,4-diazonia-2,5-diboratacyclohexane produce acetyl, alkyl, and borane derivatives, some of which have a structural analogy to choline and acetylcholine. The BOH function generally is not hydrogen bonded when the amine is quadrivalent. Notable kinetic stability towards air and aqueous environments is observed for acetyl derivatives.