Heterocyclization of Derivatives of 4-Oxoalkanoic Acids to 1,5-Disubstituted Pyrrolin-2-ones

Conditions were developed for the synthesis and production of 1-aryl-5-alkyl(aryl)-3H- and 1-aryl-5-alkyl(aryl)-5H-pyrrolin-2-ones from the amides and esters of 4-oxoalkanoic acids. It was established that the yield and ratio of the 3H and 5H isomers depend on the substrate employed in the reaction.     

Radical addition reaction of alcohols to 1-(4-nitrophenyl)-5H-pyrrolin-2-one

Quantum chemical calculations of the parameters of the 1-(4-nitrophenyl)-5H-pyrrolin-2-one molecule have been carried out by the MNDO method. The radical addition reaction of aliphatic, alicyclic, and aromatic alcohols to 1-(4-nitrophenyl)-5H-pyrrolin-2-one with the formation of 3- and 4-substituted pyrrolidones has been investigated.Kuban State Technological University, Krasnodar 350072, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 934–938, July, 1998.     

Reactions of N,N-Disubstituted 5-Arylmethylidene-2-amino-thiazol-4(5H)-ones with CH Acids

Summary.  N,N-Disubstituted 5-arylmethylidene-2-aminothiazol-4(5H)-ones reacted with diethyl malonate, ethyl benzoylacetate, acetylacetone, or cyclopentadiene in refluxing toluene and in presence of powdered sodium to give the respective 5-arylmethylidene-2′-amino-2,5′-bithiazolylidene-4,4′-dione derivatives in moderate yields. 5-Benzylidene-2-morpholin-4-yl-2-thiazol-4(5H)-one reacted with malononitrile in toluene and in presence of powdered sodium under mild conditions to afford the 1:1 adduct, benzylmalononitrile, and 2-morpholin-4-yl-2-thiazol-4(5H)-one. However, similar treatment of 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-one with malononitrile yielded the 2,5′-bithiazolylidene-4,4′-dione derivative together with 4-methoxyphenylmethylidene malononitrile. Treatment of 5-benzylidene- and 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-ones with 3-phenyl-4-oxo-2-thioxo-1,3-thiazolidine in refluxing toluene and in presence of powdered sodium produced 5-arylmethylidene-3-phenyl-4-oxo-2-thioxo-1,3-thiazolidines in good yields. The structures of all products were deduced from microanalytical and spectroscopic data, mechanistic details are discussed. Corresponding author. E-mail: kamalkandeel@hotmail.com Received November 5, 2001. Accepted (revised) December 17, 2001     

Synthesis of Arylidene Derivatives of 1-Aryl-3H-pyrrol-2-ones

The aminolysis of 5-aryl-3-arylidene-3H-furan-2-ones by the action of aromatic amines leads to the formation of substituted amides of 4-oxo acids, the subsequent azacyclization of which in the presence of acetic anhydride leads to the formation of 1,5-diaryl-substituted 3-arylidene-3H-pyrrol-2-ones. The mechanism of the occurring and alternative transformations is discussed.     

Condensation reactions at the methylene group of 1-(4-nitrophenyl)-pyrrolin-2-one and 1-(4-nitrophenyl)-pyrrolin-2-onium perchlorate

The interaction has been investigated of 1-(4-nitrophenyl)pyrrolin-2-one with aromatic aldehydes in acetic anhydride in the presence of catalytic amounts of pyridine. 1-(4-Nitrophenyl)pyrrolinium perchlorate has been synthesized and was put into a condensation reaction with aromatic aldehydes. As a result 5-arylidene-1-(4-nitrophenyl)pyrrolin-2-onium perchlorates were obtained. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1015–1021, July, 2006.     

1-Oxa-3-azapentalen-2-ones as Precursors of cis-2-Amino Alcohols: Synthesis from Propargyl Alcohols, CO2, and Amines Using an Intramolecular Amidoalkylation Reaction of Oxazolidin-2-ones

The reaction of 5-methyl-5-(4-methyl-3-pentenyl)-4-methylene-1,3-dioxolan-2-one with primary amines gives the corresponding 4-hydroxy-4-methyloxazolidin-2-ones. These undergo an intramolecular amidoalkylation reaction to form 1-oxa-3-azapentalen-2-ones which are potential precursors of cyclopentanyl cis-2-amino alcohols.     

1,3-Dipolar cycloaddition of diarylnitrones to 1-(4-nitrophenyl)-5H-pyrrolin-2-one

The reaction of diarylnitrones with 1-(4-nitrophenyl)-5H-pyrrolin-2-one to give 2-oxa-6-oxo-3-phenyl-4-(R-phenyl)-7-(4-nitrophenyl)-3,7-diazabicyclo(3,3,0)octanes has been examined. The structures of the products were established by NMR and IR spectroscopy, and x-ray diffraction studies. The stereoselectivity of the reaction is due to exo-approach of the reactants with cis-stereospecific addition of the trans-forms of the C,N-diarylnitrones to the pyrrolinone double bond.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1675–1678, December, 1990.     

2-Trif luoromethyl-4H-thiochromen-4-one and 2-trif luoromethyl-4H-thiochromene-4-thione: Synthesis and reactivities

2-Trifluoromethyl-4H-thiochromene-4-thione obtained from 2-trifluoromethyl-4H-thiochromen-4-one and P₂S₅ reacts with aromatic amines, hydrazine hydrate, phenylhydrazine, and hydroxylamine at the C(4) atom of the chromene ring to give the corresponding anils, azine, hydrazones, and oxime of thiochromone. 2-Trifluoromethyl-4H-thiochromen-4-one is oxidized by hydrogen peroxide in AcOH into 4-oxo-2-trifluoromethyl-4H-thiochromene 1,1-dioxide and reduced by NaBH₄ to 2-trifluoromethyl-4H-thiochromen-4-ol or cis-2-(trifluoromethyl)thiochroman-4-ol. When treated with hydrazine hydrate, thiochromen-4-one gives 3(5)-(2-mercaptophenyl)-5(3)-trifluoromethylpyrazole. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 504–509, March, 2006.     

A new method for the synthesis of N-substituted (4-oxo-4,5,6,7-tetrahydroindol-3-yl)acetic acids

A new method for the synthesis of N-substituted 2-(4-oxo-4,5,6,7-tetrahydroindol-3-yl)acetic acids was developed. Alkylation of cyclic 1,3-diketones with 3,5,5,5-tetrachloropentan-2-one affords 1,4-diketones, which undergo cyclization with different primary amines into N-substituted 3-(2,2,2-trichloroethyl)-4,5,6,7-tetrahydroindol-4-ones. Acid hydrolysis of the latter gives the corresponding indol-3-ylacetic acids. The structures of the compounds obtained were confirmed by ¹H and ¹³C NMR data.     

Synthesis of isomeric 2-oxazolidinones from (1<Emphasis Type="Italic">R</Emphasis>,2<Emphasis Type="Italic">R</Emphasis>)-and (1<Emphasis Type="Italic">S</Emphasis>,2<Emphasis Type="Italic">S</Emphasis>)-2-amino-1-(4-nitrophenyl)-1,3-propanediols

A synthesis is reported for (4R,5R)-and (4S,5S)-4-hydroxymethyl-5-(4-nitrophenyl)oxazolidin-2-ones and (1′R,4R)-and (1′S,4S)-4-[hydroxy(4-nitrophenyl)methyl]oxazolidin-2-ones from (1R,2R)-and (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediols. The effect of the experimental conditions on the formation of these compounds was studied. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1562–1570, October, 2007.     

One-step synthesis of 5-acetyl-2-amino-4-aryl-3-cyano-4H-pyrano[3,2-b]indoles. Molecular and crystal structure of 5-acetyl-2-amino-4-(4"-chloro-3"-nitrophenyl)-3-cyano-4H-pyrano[3,2-b]indole

A one-step procedure was developed for the synthesis of 5-acetyl-2-amino-4-aryl-3-cyano-4H-pyrano[3,2-b]indoles involving the three-component reaction of 1-acetylindol-3(2H)-one with aromatic aldehydes and malononitrile in ethanol in the presence of triethylamine as the catalyst. The structure of 5-acetyl-2-amino-4-(4"-chloro-3"-nitrophenyl)-3-cyano-4H-pyrano[3,2-b]indole was established by X-ray diffraction analysis.     

Facile one-pot synthesis of 5-aryl/heterylidene-2-(2-hydroxyethyl- and 3-hydroxypropylamino)-thiazol-4-ones via catalytic aminolysis

A multicomponent synthetic approach for 5-aryl/heterylidene-2-(2-hydroxyethylamino)- and 2-(3-hydroxypropylamino)-thiazol-4-ones starting from 2-thioxothiazolidin-4-one or 2-methylsulfanylthiazol-4-one was developed. The proposed method involves simultaneous aminolysis of 2-thioxo- or 2-methylsulfanyl groups and Knoevenagel condensation with (hetero)aromatic aldehydes using 2-aminoethanol or 3-aminopropan-1-ol as catalysts. Side-chain prototropic amino–imino tautomerism was observed for target 5-ylidene-2-alkylaminothiazol-4-ones.     

Synthesis of 2-(4-amino substituted benzylidene) indanone analogues from aromatic nucleophilic substitution (SNAr) reaction

A novel, efficient and convenient procedure has been developed for the synthesis of 2-(4-amino-substituted benzylidene)indanone derivatives. In the first step, the reaction of 4-fluorobenzaldehyde with 5, 6-dimethoxy-2, 3-dihydro-1H-inden-1-one in the presence of NaOH in EtOH was described. In the next step, a variety of aliphatic and aromatic amines were reacted with 2-(4-fluorobenzylidene)-5, 6-dimethoxy-2, 3-dihydro-1H-Inden-1-one via aromatic substitution (S_NAr) reaction to produce 2-(4-aminobenzylidene)-5, 6-dimethoxy-2, 3-dihydro-1H-Inden-1-one derivatives as a novel class of 1-indanones. These products have been successfully prepared in good to excellent yields. ^1?H and ^13?C NMR, FT-IR spectroscopy and CHN analysis supported the proposed structures of the products.     

Synthesis of 5-[2-(Phenoxy)ethyl] Derivatives of 6-Methyluracil, 6-Methyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one,and 2-Imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one

A synthesis of novel derivatives of 6-methyluracil, 6-methyl-2-thioxo-, and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one containing a 2-(phenoxy)ethyl substituent at position 5 of the pyrimidine ring has been carried out. It was found that 5-[2-(phenoxy)ethyl] derivatives of 6-methyl-2-thioxo- and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one are obtained by the condensation of the corresponding ethyl 3-oxo-2-(2-phenoxyethyl)butanoates with thiourea or guanidine. 6-Methyl-5-[2-(phenoxy)ethyl]uracils can be prepared by treating 6-methyl-5-[2-(phenoxy)ethyl]-2-thioxo-2,3-dihydro-1H-pyrimidin-4-ones with an excess of aqueous monochloroacetic acid solution. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1213–1217, August, 2005.     

2-Amino-5,5-bis(hydroxymethyl)-1,3-thiazol-4(5H)-one and its spirodioxane compounds in the Mannich reaction

It was found that the aminomethylation of 2-amino-5,5-bis(hydroxymethyl)-1,3-thiazol-4(5H)-one and its spiro analogs using primary amines is accompanied by cyclization at the amidine fragment of the molecule with annelation of a tetrahydrotriazine ring. When using secondary amines the aminomethylation occurs at the exocyclic nitrogen atom. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1252–1260, August, 2006.     

2-Polyfluoroalkylchromones. 6. Synthesis of substituted 2-morpholino-2-trifluoromethylchroman-4-ones

Morpholine adds smoothly at the double bond of substituted 5- and 8-nitro-2-trifluoromethylchromones to form the corresponding 2-morpholino-2-trifluoromethylchroman-4-ones. 6-Methoxy-5-nitro-2-trifluoromethylchromone adds also benzylamine, whereas 7-methoxy-8-nitro-2-trifluoromethylchromone undergoes ring opening under the action of benzylamine to give 3-benzylamino-4,4,4-trifluoro-1-(2-hydroxy-4-methoxy-3-nitrophenyl)but-2-en-1-one.     

Reactions of sulfonamides with 4,5-dihydroxyimidazolidin-2-ones

The interaction of sulfonamides with 4,5-dihydroxyimidazolidin-2-ones was studied for the first time. The earlier unknown 4,4′-sulfonyldiiminobis(1,3-dialkylimidazolidin-2-ones) and 4(5)-aryl(alkyl)-sulfonyliminoimidazolidin-2-ones were synthesized. A probable pathway of the reaction was proposed. 1,3-Diethyl-4,5-dihydroxyimidazolidin-2-one was isolated and described. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1604–1607, August, 1998.     

Imino <Emphasis Type="Italic">Diels-Alder</Emphasis> Reactions: Efficient Synthesis of 2-Aryl-4-(2′-oxopyrrolidinyl-1′)-1,2,3,4-tetrahydroquinolines catalyzed by Antimony(III) Sulfate

Summary. Antimony(III) sulfate is found to catalyze the imino Diels-Alder reaction of Schiff’s bases with N-vinylpyrrolidin-2-one to afford 2-aryl-4-(2′-oxopyrrolidinyl-1′)-1,2,3,4-tetrahydroquinolines. One-pot synthesis of 1,2,3,4-tetrahydroquinolines from 3-nitro benzaldehyde and aromatic amines with N-vinylpyrrolidin-2-one catalyzed by antimony(III) sulfate is also reported. This catalyst is inexpensive, easily available, and it was also found that catalyst could be recovered quantitatively and reused without much loss of catalytic activity.     

Synthesis and Intramolecular Cyclization of N-Substituted 2-Amino-4-aryl-4-oxo-2-butenoic Acids

Treating 4-aryl-2,4-dioxobutanoic acids with aromatic amines, 4-aminoantipyrine, and benzophenone hydrazone furnished N-substituted 2-amino-4-aryl-4-oxo-2-butenoic acids that existed in solutions in enaminoketone and iminoketone forms. The acids obtained underwent in the presence of acetic anhydride cyclization into N-substituted 5-aryl-3-imino-3H-furan-2-ones.     

Synthesis of 6-amino-4-aryl-5-cyano-3-(3-cyanopyridin-2-ylthiomethyl)-2,4-dihydropyrano[2,3-c]pyrazoles and their hydrogenated analogs. Molecular structure of 6-amino-5-cyano-3-(3-cyano-4,6-dimethylpyridin-2-ylthiomethyl)-4-(2-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole

Substituted 3-hydroxypyrazoles, which were prepared based on ethyl esters of substituted 4-(pyridin-2-ylthio)- or 4-(1,4-dihydropyridin-2-ylthio)acetoacetic acids and hydrazine hydrate, were used in the synthesis of 6-amino-4-aryl-5-cyano-3-(pyridin-2-ylthiomethyl)-2,4-dihydropyrano[2,3-c]pyrazoles. The molecular and crystal structure of 6-amino-5-cyano-3-(3-cyano-4,6-dimethylpyridin-2-ylthiomethyl)-4-(2-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole was established by X-ray diffraction analysis.