Reaction of Fluoro-containing 3-Oxoesters with Benzaldehyde

Fluorinated 3-oxoesters in reactions with benzaldehyde depending on conditions afford either 2-benzylidene-3-fluoroalkyl-3-oxoesters or 3,5-dialkoxycarbonyl-2,6-dihydroxy-2,6-difluoroalkyl-4-phenyltetrahydropyrans. The latter were also obtained by treating 3-oxoesters with 2-benzylidene-3-oxoesters. Pentafluorobenzoylacetate with benzaldehyde furnishes 3,5-diethoxycarbonyl-2-pentafluorophenyl-4-phenyl-7,8,9,10-tetrafluoro-4,5-dihydrobenzo[b]oxacin-6-one.     

Alkyl 3-fluoroalkyl-3-oxopropionates in reactions with azolyldiazonium salts

Alkyl 3-fluoroalkyl-3-oxopropionates react with antipyrinyldiazonium chloride to form 2-antipyrinylhydrazono-3-fluoroalkyl-3-oxopropionates. The use in these reactions of hetaryldiazonium salts, containing NH group in the α position, leads to alkyl 7-fluoroalkyl-7-hydroxy-4,7- dihydroazolo[5,1-c]triazine-6-carboxylates. 3-Amino-1H-1,2,4-triazole, 3-amino-4-ethoxycar- bonyl-1H-pyrazole, and 5-amino-4-ethoxycarbonyl-1H-imidazole were used as the heterocyclic component. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 599–603, March, 2008.     

Reactions of benzimidazole-2-carbaldehyde with enamines

Benzimidazole-2-carbaldehyde reacts with 1-morpholinocyclohexene, 1-morpholinocyclopentene, and aminocrotonic ester upon heating to form 4a,11-dimorpholino-1,2,3,4,11,11a-hexahydro-4aH-indolo[1,2-a]benzimidazole, 2-(2-morpholino-4,5-dihydrofulvenyl)benzimidazole, and 4-(benzimidazol-2-yl)-3,5-diethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine, respectively. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 566–571, March, 1999.     

Synthesis of 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones

The reactions of 1-substituted 2-nitro-3-phenylaminoprop-2-en-1-ones with cyanothioacetamide afforded the corresponding 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones, which were used for the synthesis of 6-substituted 3-cyano-2-methylthio-5-nitropyridines and 7-substituted 4-hydroxy-8-nitropyrido[2",3":4,5]thieno[2,3-b]pyridin-2(1H)-ones.     

Synthesis and Alkylation of Piperidinium 4,5-trans-3-Cyano-6-hydroxy-4-(2-iodophenyl)-6-methyl-5-(2-methylphenyl)carbamoyl-1,4,5,6-tetrahydropyridine-2-thiolate. Molecular and Crystal Structure of 3-(2-Iodophenyl)-2-(4-phenyl-2-thiazolyl)acrylonitrile

The reaction of o-iodobenzaldehyde, cyanothioacetamide, and N-acetoacetyl-o-toluidine in the presence of piperidine gave piperidinium 4,5-trans-3-cyano-6-hydroxy-4-(2-iodophenyl)-6-methyl-5-(2-methylphenyl)carbamoyl-1,4,5,6-tetrahydropyridine-2-thiolate used in the synthesis of substituted 4,5-trans-2-alkylthiotetrahydropyridines and 2-(2-thiazolyl)acrylonitriles. The structure of 3-(2-iodophenyl)-2-(4-phenyl-2-thiazolyl)acrylonitrile was studied using X-ray diffraction structural analysis.     

4-(3-Cyanopyridin-2-ylthio)acetoacetates in synthesis of heterocycles

Substituted 2-amino-4-aryl-3-cyano-5-oxo-5,6-dihydro-4H-pyrano[2,3-d]pyrido[3",2":4,5]thieno[3,2-b]pyridines were synthesized by the reactions of 4-hydroxy-1H-thieno[2,3-b;4,5-b]dipyridin-2-ones with arylidenemalononitriles or by the three-component reactions of hydroxythienodipyridinones with aldehydes and malononitrile in DMF in the presence of triethylamine. Methods for syntheses of substituted 3-alkoxycarbonyl-6-amino-4-aryl-2-(3-cyanopyridin-2-ylthiomethyl)-4H-pyrans were developed on the basis of the reactions of 4-(3-cyanopyridin-2-ylthio)acetoacetates and arylidenemalononitriles or aldehydes and malononitrile. Ethyl 4-(3-cyanopyridin-2-ylthio)acetoacetate and 4-methoxybenzylidenecyanothioacetamide were used for the synthesis of 6-(pyridin-2-ylthiomethyl)-3-cyanopyridine-2(1H)-thione.     

Formation of pyridines fromN-methylpyrimidinium iodide and enaminoesters

The reaction ofN-methylpyrimidinium iodide with enaminoesters yields a mixture of 3-ethoxycarbonyl-2-methylpyridine and 3,5-diethoxycarbonyl-2,6-dimethylpyridine. Mechanisms of the transformations of the pyrimidine ring found are suggested.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1318–1321, July, 1995.     

Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor^® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.     

Abnormal ring closure and oxidation in situ of 2-hydroxy-5-nitrobenzaldehyde in the hantzsch synthesis

The Hantzsch condensation of 2-hydroxy-5-nitrobenzaldehyde, ethyl acetoacetate and ammonia gave the hitherto unknown 2-methyl-3-ethoxycarbonyl-4-ethoxycarbonylmethyl-6-(2-hydroxy-5-nitrophenyl)-pyridine via an unusual condensation and oxidation in situ.     

Stereoselective Synthesis and Alkylation of N-Methylmorpholinium 4,5-trans-4-(2-chlorophenyl)-3-cyano-6-hydroxy-5-(2-thenoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine-2-thiolate. Molecular and Crystal Structure of 4,5-trans-4-(2-chlorophenyl)-3-cyano-6-hydroxy-2-methallylthio-5-(2-thenoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine

The condensation of 2-chlorobenzaldehyde with cyanothioacetamide and 2-thenoyltrifluoroacetone in the presence of N-methylmorpholine takes place stereoselectively and leads to the formation of N-methylmorpholinium 4,5-trans-4-(2-chlorophenyl)-3-cyano-6-hydroxy-5-(2-thenoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine-2-thiolate. The latter was used to synthesize the corresponding 2-alkylthiotetrahydropyridines. The structure of 4,5-trans-4-(2-chlorophenyl)-3-cyano-6-hydroxy-2-methallylthio-5-(2-thenoyl)-6-trifluoromethyl-1,4,5,6-tetrahydropyridine was determined by X-ray crystallographic analysis.     

Ambident Properties of 4-Substituted Thiosemicarbazides in Condensations with Fluoroacetic Acids

4-Substituted thiosemicarbazides react with di- and trifluoroacetic acids to give the corresponding 3-fluoroalkyl-4,5-dihydro-1,2,4-triazole-5(1H)-thiones. Condensation of 4,4-disubstituted thiosemicarbazides with trifluoroacetic acid leads to formation of 2-amino-5-trifluoromethyl-1,3,4-thiadiazoles.     

One-step synthesis of N-alkyl-2-aryl-2-oxoacetamides and N,N-dialkyl-2-aryl-4H-1,3-benzodioxine-2,4-dicarboxamides

Alkyl isocyanides react with 2-hydroxybenzaldehyde or 2-hydroxy-5-nitrobenzaldehyde to afford N-alkyl-2-aryl-2-oxoacetamides and N²,N⁴-dialkyl-2-aryl-4H-1,3-benzodioxine-2,4-dicarboxamides in nearly 1:1 ratios. Treatment of 2,6-dimethylphenyl isocyanide with 2-hydroxy-5-nitrobenzaldehyde affords only the 2-oxoacetamide derivative.     

Synthesis of some schiff bases of 3-aroyl-6-aryl-4-hydroxy-2H-pyran-2-ones

Summary The reaction of 3-aroyl-6-aryl-4-hydroxy-2H-pyran-2-ones (Ar=p-tolyl, 1,1-biphenyl-4-yl or thienyl) with aniline and substitutedo-phenylenediamine (R=H, CH₃ or Cl) yields a series of new Schiff bases2a–f in 51–72% yield. Bromination of1a gave the 5-bromo derivative1c, while the compounds1a,1b,2b,2e, and2f were converted into 2,6-diaryl-4H-pyran-4-ones3a–c. All products have been fully characterized.

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Synthese von Schiff'schen Basen von 3-Aroyl-6-aryl-4-hydroxy-2H-pyran-2-onen

Zusammenfassung Die Reaktion von 3-Aroyl-6-aryl-4-hydroxy-2H-pyran-2-onen (Ar=p-Tolyl, 1,1-Biphenyl-4-yl oder Thienyl) mit Anilin und substituierteno-Phenylendiaminen liefert neue Schiff'sche Basen2a–f/bd in 51–72% Ausbeute. Bromierung von1a gab das 5-Bromderivate1c, während die Verbindungen1a,1b,2b,2e und2f in 2,6-Diaryl-4H-pyran-4-onen3a–c übergeführt wurden. Alle Produkte wurden voll charakterisiert.

     

Preparation and properties of piperidine salts of 6-hydroxy-4,6-diaryl-5-ethoxycarbonyl-3-cyanopiperidine-2-thiones

Alkylation of piperidine salts of 6-hydroxy-4,6-diaryl-5-ethoxycarbonyl-3-cyanopiperidine-2(1H)-thiones yielded 6-hydroxy-2-alkylthio-4,6-diaryl-5-ethoxycarbonyl-3-cyano-3,4,5,6-tetrahydropyridines which were dehydrogenated with the formation of 2-methylthio-1,4- and 4,5-dihydropyridines. The oxidation of the compounds prepared has been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–80, January, 1987.     

Direct synthesis of 3-fluoroalkyl-2,6-diethoxycarbonyl phenols

Cyclocondensation of α-fluoroalkyl ketones or α-fluoroalkyl aldehyde (1) and diethyl 1,3-acetonedicarboxylate (2) affords 3-fluoroalkyl-2,6-diethoxycarbonyl-5-alkyl-phenols (3) in good yields. This provides a novel method for the preparation of meta-fluoroalkyl polysubstituted phenols.     

The reactions of aroylpyruvic acids and their derivatives witho-aminophenyldiphenylmethanol

Aroylpyruvic acids and their methyl esters react witho-aminophenyldiphenylmethanol to form 4-aryl-2-[2-(1-hydroxydiphenylmethyl)phenylamino]-4-oxobut-2-enoic acids and their esters. The α-enamino acids obtained undergo intramolecular heterocyclization in the presence of Ac₂O to affort substituted 4,5-dihydrobenzo[e][1,4]oxazepin-3(1H)-ones. The reaction of 5-arylfuran-2,3-diones witho-aminophenyldiphenylmethanol leads to products of decyclization, 2-(1-hydroxydiphenylmethyl)phenylamides of 4-aryl-2-hydroxy-4-oxobut-2-enoic acid, which upon heating in AcOH or Ac₂O yield 3-aroylacetyl-1,1-diphenyl-1H-benzo[d][1,3]oxazines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2317–2319, November, 1998.     

Cross-condensation of derivatives of cyanoacetic acid and carbonyl compounds. 2. One-pot synthesis of substituted 2-amino-7-methyl-5-oxo-4,5-dihydropyrano[4,3-b]pyrans in ethanol and ionic liquid [bmim][PF6]

The three-component reaction of 4-hydroxy-6-methylpyran-2(2H)-one with cyanoacetic acid derivatives and carbonyl compounds in EtOH or in the ionic liquid, viz., 1-butyl-3-methylimidazolinium hexafluorophosphate ([bmim][PF₆]), affords substituted 2-amino-7-methyl-5-oxo-4,5-dihydropyrano[4,3-b]pyrans. The yield of substituted pyrano[4,3-b]pyrans in [bmim][PF₆] is by 10—14% higher than that in EtOH.     

Reactions of 2-diaminomethylidenecyclohexane-1,3-diones with diethyl malonate

The debenzoylation of 2-[(amino)(benzoylamino)methylidene]cyclohexane-1,3-diones (addition products of cyclohexane-1,3-diones with benzoylcyanamide) affords the corresponding 2-diaminomethylidenecyclohexane-1,3-diones. The latter act as N,N-dinucleophiles in reactions with diethyl malonate in the presence of MeONa to form 6-hydroxy-2-(2,6-dioxocyclohexylidene)-1,2-dihydropyrimidin-4(3H)-ones. This reaction performed at 200 °C in the absence of bases results in the subsequent self-condensation of the dihydropyrimidinones to give 4,5′-bipyrimidine derivatives.     

The synthesis of 5-substituted 3-benzoylamino-6-(2-substituted amino-1-ethenyl)-2H-pyran-2-ones and their transformations into 2H-pyrano[3,2-c]pyridine derivatives

A new approach to the 2H-pyrano[3,2-c]pyridine system is described. 5,6-Disubstituted 3-benzoylamino-2H-pyran-2-ones 3a,b , prepared from the corresponding 1,3-dicarbonyl compounds 1a,b and methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate ( 2 ), were converted into 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one ( 4a ) and 5-acetyl derivative 4b . The exchange of the dimethylamino group in 4a,b with aromatic amines 5a-f,m , héteroaromatic amines 5g-i , and benzylamines 5j-l produced 5-ethoxycarbonyl-3-benzoylamino-6-(2-arylamino- or heteroarylamino-or benzylamino-1-ethenyl)-2H-pyran-2-ones 6a-l , and its 5-acetyl analog 6m . The compounds 6 were cyclized in basic media into 2H-pyrano[3,2-c]pyridine derivatives 7a-h . Analogously react also α-amino acid derivatives 8a-c and 11 as nitrogen nucleophiles producing 9a-c, 10 and 12 .     

Synthesis and structure of new 3-pyrazolinylcoumarins and 3-pyrazolinyl-2-quinolones

The reactions of substituted 3-cinnamoyl-4-hydroxycoumarins and 3-cinnamoyl-4-hydroxy-2-quinolones with different phenylhydrazines gave 3-hetaryl-1H-4,5-dihydropyrazoles. The product structures were studied by ¹H NMR spectroscopy and mass spectrometry. 4-Hydroxy-3-pyrazo-linylcoumarins exist in DMSO as two tautomers (4-enol and chromane-2,4-dione), while 4-hydroxy-3-pyrazolinyl-2-quinolones exist only in the enol form. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1479–1486, July, 2008.