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.     

One pot four-component reaction for the efficient synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]-3′-carboxylate derivatives

A novel one pot protocol has been developed to synthesize various spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]-3′-carboxylate derivatives from the four-component reaction of isatin, malononitrile, hydrazine derivatives and dialkyl acetylenedicarboxylates. In this process two C–C bonds, two C–N bonds and one C–O bond have formed in one pot. The notable features of this protocol are simple and environmentally benign reaction condition, easy isolation of products, applicable to a wide range of readily available starting materials and good yields.     

Convenient DABCO-catalyzed one-pot synthesis of multi-substituted pyrano[2,3-c]pyrazole dicarboxylates

We developed an efficient and simple one-pot synthesis of functionalized multi-substituted 2,4-dihydro-pyrano[2,3-c]pyrazole dicarboxylates from β-ketoesters, hydrazine, dimethyl acetylenedicarboxylate and malononitrile in EtOH. This four-component one-pot reaction carried out in the presence of DABCO catalyst showed advantages over a one-pot three-component method in its simple procedure, high yield and low toxicity.     

Convenient synthesis of spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] and spiro[acenaphthyl-3,4'-pyrano[2,3-c]pyrazoles] via fourcomponent reaction

The base promoted four-component reaction of hydrated hydrazine, dimethyl acetylenedicarboxylate, isatines and malononitrile (ethyl cycanoacetate) in ethanol afforded polysubstituted spiro[indoline-3,4‘-pyrano[2,3-c]pyrazoles] and spiro[acenaphthyl-3,4-pyrano[2,3-c]pyrazoles]     

A novel one-pot synthesis of spiro[indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine] diones using recyclable bioglycerol-based sulfonic acid functionalized carbon catalyst

A novel, simple, and efficient synthetic protocol has been developed for the synthesis of spiro[indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine] diones, by using bioglycerol-based sulfonic acid functionalized carbon as a recyclable catalyst, devoid of moisture sensitive metal catalysts and corrosive acidic reagents. This new protocol produces novel heptacyclic spirooxindole derivatives in good to excellent yields, with operational simplicity and recycling of the catalyst in comparison to predictable pentacyclic compounds. The catalyst can be prepared by a simple adoptable procedure from an inexpensive and readily available bio-glycerol and found to be recoverable and reusable up to four cycles without any loss of activity.     

A green and convenient approach for the synthesis of methyl 6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates via a one-pot, multi-component reaction in water

A green and efficient one-pot, four-component synthesis of methyl 6-amino-5-cyano-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates in water is described. The method is catalyst-free, atom-economical, and does not involve tedious work-up or purification affording the target compounds in good yields.     

New four-component reactions in water: a convergent approach to the metal-free synthesis of spiro[indoline/acenaphthylene-3,4′-pyrazolo[3,4-b]pyridine derivatives

New four-component domino reactions are described that allow the one-pot synthesis of spiro[indoline/acenaphthylene-3,4′-pyrazolo[3,4-b]pyridine derivatives from the reaction of phenylhydrazine, 3-aminocrotononitrile, isatin/acenaphthylene-1,2-dione, and cyclic 1,3-dicarbonyl compounds, including cyclohexane-1,3-diones, barbituric acid, and 2-thioxodihydropyrimidine-4,6(1H,5H)-dione, in the presence of (±)-camphor-10-sulfonic acid (CSA). These processes take place in water and involve the generation of two rings and five new bonds (two C-C, two C-N and one CN) in a single synthetic operation, with expedient work-up and diminished waste generation due to the absence of extraction and purification steps.     

One-pot reaction for the concise synthesis of spiro[benzofuran-2,2′-naphthalen]-1′-one derivatives

A novel one-pot two-step protocol has been developed to synthesize various spiro[benzofuran-2,2′-naphthalen]-1′-one derivatives from the three-component reaction of tetralones, 2-hydroxyphenyl functionalized α,β-unsaturated ketones, and iodine. One C–C bond and one C–O bond have formed during this process. The notable features of this protocol are simple and mild reaction conditions, applicable to a wide range of readily available starting materials, good yields (up to 91%), and excellent stereoselectivities (up to 97:3).     

A novel and efficient one-pot synthesis of furo[3′,4′:5,6]pyrido[2,3-c]pyrazole derivatives using organocatalysts

A novel approach to one-pot synthesis of dihydrofuro[3′,4′:5,6]pyrido[2,3-c]pyrazole and indeno[2′,1′:5,6]pyrido[2,3-c]pyrazole derivatives have been investigated using organocatalysts that are recyclable. This new protocol has the advantages of environmental friendliness, higher yield, low cost, as well as convenient operation. The catalytic efficiency of various small organocatalysts such as l-proline, trans-4-hydroxy-l-proline, l-thiaproline, cinchonidine, (+)-cinchonine, and dl-2-phenylglycine has also been studied.     

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.     

Efficient synthesis of diarylidene octahydroacridines by one-pot multi-component tandem reactions

A one-pot multi-component reaction is developed for the efficient synthesis of 4,5-dibenzylidene octahydroacridines in high yields. The reaction is performed by the tandem reaction of three molar equivalent aromatic aldehydes with two molar equivalent 4-alkylcyclohexanone in the system of NH₄OAc/HOAc under microwave irradiation.      

An efficient one-pot,multi-component diastereoselective synthesis of functionalized cyclopenta[c]chromenes

A novel one-pot, multi-component diastereoselective synthesis of functionalized cyclopenta[c]chromenes is described. This transformation proceeds via a Michael addition-cyclization reaction sequence between trialkyl phosphites, dialkyl acetylenedicarboxylates and in situ generated 2-(1-(2-oxo-2H-chromen-3-yl)alkylidene)malononitriles from the condensation of 3-acyl-2H-chromen-2-ones and malononitrile.     

Application of p-TSA in the one pot synthesis of N-methyl-3-nitro-aryl-benzo[4,5]imidazo[1,2-a]pyrimidin-2-amine

A simple, efficient, eco-friendly, and cost-effective method has been developed for the synthesis of N-methyl-3-nitro-aryl-benzo[4,5]imidazo[1,2-a]pyrimidin-2-amine derivatives using 2-aminobenzimidazole, aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine, in the presence of catalytic amount of p-toluenesulfonic acid (p-TSA) in ethanol at 80?°C conditions. The advantages of this method are the use of an inexpensive and readily available catalyst, shorter reaction times, a wide range of functional group tolerance, and high yield of products via a simple experimental and work-up procedure.     

Synthesis of 1′-aryl-2′-(2-oxoindolin-3-yl)spiro[indoline-3,5′-pyrroline]-2,3′-dione via one-pot reaction of arylamines, acetone, and isatins

An efficient synthetic method for 1′-aryl-2′-(2-oxoindolin-3-yl)spiro[indoline-3,5′-pyrroline]-2,3′-diones was successfully developed via the one-pot domino reaction of arylamines, acetone, and isatins in acetic acid. The reaction mechanism involved the sequential Michael addition and ring closure of the in situ formed 3-N-aryliminoisatin and isatylidene acetone.     

CuCl-catalyzed one-pot synthesis of 5,6-dihydropyrazolo[1,5-c]quinazolines

A simple and efficient procedure for the preparation of 5,6-dihydropyrazolo[1,5-c]quinazolines via CuCl-catalyzed tandem reaction of 5-(2-bromoaryl)-1H-pyrazoles with aldehydes and aqueous ammonia under nitrogen atmosphere has been developed. The usefulness of this novel methodology was showcased by its successful application in the preparation of a potential Eg5 inhibitor.     

A regioselective three-component reaction for synthesis of novel 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione derivatives

A ring opening and regioselective three-component reaction of isatoic anhydride, isatins, and aromatic or aliphatic primary amines in the presence of catalytic amount of KAl(SO₄)₂·12H₂O (alum) to yield a novel series of 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione is described.     

Indium(III)chloride catalyzed synthesis of novel 1H-pyrazolo[1,2-b]phthalazine-5,10-diones and 1H-pyrazolo[1,2-a]pyridazine-5,8-diones under solvent-free condition

An efficient, inexpensive and environmentally friendly synthesis of novel 3-amino-2-benzoyl-1-aryl-1H-pyrazolo[1,2-b]phthalazine-5,10-dione and 3-amino-2-benzoyl-1-aryl-1H-pyrazolo[1,2-a]pyridazine-5,8-dione derivatives has been developed via one-pot three-component reaction of phthalhydrazide or maleic hydrazide, aldehydes and arylacetonitrile in the presence of catalytic amount of InCl₃ as a Lewis acid catalyst under solvent-free conditions. The most important features of the present protocol are mild reaction conditions, short reaction times, high yields, and a wide range of functional group tolerance.     

Synthesis of novel fluorescent benzo[a]pyrano[2,3-c]phenazine and benzo[a]chromeno[2,3-c]phenazine derivatives via facile four-component domino protocol

An efficient and practical route to novel fluorescent benzo[a]pyrano[2,3-c]phenazine framework has been developed by one-pot, four-component reaction of 2-hydroxynaphthalene-1,4-dione, 1,2-phenylenediamines, aromatic aldehydes, and Meldrum’s acid in glacial acetic acid at 70 °C. Photophysical studies of these compounds have been reported. Reactions involving cyclohexane-1,3-dione/5-methylcyclohexane-1,3-dione/dimedone in the place of Meldrum’s acid yielded corresponding benzo[a]chromeno[2,3-c]phenazine derivatives. Crystal structure of 3k established the regioisomer formed. Mild reaction conditions, good yields, short reaction time, and easy separation are some of the salient features of the present protocol.     

One-pot synthesis of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives using multi-component reactions

In this work, a new series of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives have been synthesized using an aromatic 1,2-diamine, Meldrum's acid, an isocyanide, and an arylidene malononitrile (or an aldehyde and malononitrile instead of an arylidene malononitrile) in CH₂Cl₂ at ambient temperature. Synthesis of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine proceeded via four- and five-component reactions; while the synthesis of malonamide derivatives was performed using five- and six-component reactions. In addition, a new series of the malonamide derivatives have been prepared using an aldehyde, malononitrile, Meldrum's acid, an isocyanide, and two molecules of 1,4-diamine via a six-component reaction. These procedures provide alternative methods to the synthesis of a new series of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives.     

A one-pot synthesis of 3-methyl-5-aryl-4H-pyrrolo[2,3-d]-isoxazoles

Sharpless epoxidation of 4-amino-3-methyl-5-styrylisoxazoles 1 resulted in the formation of 3-methyl-5-aryl-4H-pyrrolo[2,3-d]-isoxazoles 4 in a one-step reaction. The reaction initially involves epoxide formation, followed by ring-opening and cyclization. Finally dehydration leads to the title compounds. The pyrrolo[2,3-d]-isoxazoles 4 were also synthesized via an alternative procedure.