Preparation of 1-aryl-2-methyl-3-carbethoxy-4,5-dioxo-6-bromoindoles

1-Aryl-2-methyl-3-carbethoxy-5-hydroxy-6-bromoindoles are oxidized by nitric acid to 1-aryl-2-methyl-3-carbethoxy-4,5-dioxo-6-bromoindoles, while 1,2-dimethyl-3-carbethoxy-5-hydroxy-6-bromoindole is converted to the 4,6-dinitro derivative under similar conditions.     

Synthesis of 2-carbethoxy-3-methyl-4-hydroxybenzofuran derivatives

A number of 2-.carbethoxy-3-methylbenzofuran derivatives were synthesized. A 5,5-gem-dibromo derivative was obtained in the bromination of 2-carbethoxy-3-methyl-4-oxo-4, 5,6,7,tetrahydrobenzofuran. Dehydrobromination of this, dibromo derivative gave 2-carbethoxy-3-methyl-4-hydroxy-5-bromobenzofuran. Depending on the structure of the starting compound and the brominating agent, the bromine in the bromination of 2-carbethoxy-3-methyl-4-hydroxy- and 4-acetoxybenzofurans with bromine and N-bromosuccinimide is incorporated either in the methyl group or in 5 and 7 positions of the benzofuran ring. The nitration of 2-carbethoxy-3-methyl-4-hydroxybenzofuran and its bromo derivative leads to 5-nitro- and 5,7-dinitrobenzofuran derivatives. The structures of the synthesized benzofuran derivatives were established by means of the PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 27–29, January, 1980.     

Ring transformations of 4H-pyrans. Pyridines from 2-amino-4H-pyrans

Ring transformations of 4H-pyrans into pyridines are reported. Treatment of 2-amino-4,6-diaryl-3,5-dicyano-4H-pyrans (I) with nitrosylsulfuric acid brings about their transformation into 3,5-dicyano-4,6-diaryl-2-pyridones (VI) which can also be obtained from α-benzoylcinnamonitriles (IX) and cyanoacetamide. Similarly, 2-amino-4,6-diaryl-5-carbethoxy-3-cyano-4H-pyrans (II) lead to 4,6-diaryl-5-carbethoxy-3-cyano-2-pyridones (VII). Treatment of both series of pyrans with sulfuric acid results in the formation of the corresponding 3,4-dihydro-2-pyridones (IV and V). Reaction of pyrans II with ammonium acetate in acetic acid yields 2-amino-4,6-diaryl-5-carbethoxy-3-cyanopyridines (XII). Pyrans I undergo an entirely different type of reaction upon treatment with this reagent leading to 2,4,6-triaryl-3,5-dicyano-1,4-dihydropyridines (XV).     

Action of acidic and alkaline agents on dioxonaphthofuran derivatives

The action of sulfuric and polyphosphoric acids and sodium hydroxide on 3-carbethoxy-4,5-dioxonaphthofuran derivatives was studied. 2-Methyl- and 2-phenyl-3-carboxy-4,5-dioxonaphthofurans were obtained by the action of sulfuric acid on the indicated compounds. The action of alkali on 2-methyl- and 2-phenyl-3-carbethoxy-4,5-dioxonaphthofurans and 2-phenyl-4,9-dioxonaphthofurans leads to the formation of 2-hydroxy-3-acetonyl- and 2-hydroxy-3-phenacyl-1,4-dioxonaphthalenes. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 753–754, June, 1980.     

Vilsmeier formylation of 2-methyl-3 -carbethoxy-5-methoxy- and 2-methyl-5-methoxyindoles

The corresponding 6- and 3-formyl derivatives were obtained by formylation of 2-methyl-3-carbethoxy-5-methoxy- and 2-methyl-5-methoxyindole derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 339–341, March, 1971.     

Synthesis of 2-, 6-, and 7-aminomethyl derivatives in the 4,5-dihydroxybenzofuran series

The 2-, 6-, and 7-aminomethyl derivatives have been synthesized from derivatives of 4-hydroxy-5-methoxy- and 4-methoxy-4-hydroxybenzofuran. 2-Methyl-3-carbethoxy-5-methoxy-7-dimethylaminomethylbenzofuran has been converted into the 7-cyanomethyl derivative.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 23–27, January, 1986.     

Synthesis and properties of 1-aryl-1,4-dihydro-2,7-dimethyl-4-oxopyrido[2,3-d]pyrimidine-6-carboxylic acids and their derivatives

Acetylation of 2-arylamino-5-carbethoxy-6-methylnicotinonitriles gave N-acetyl-2-arylamino-5-carbethoxy-6-methylnicotinonitriles, which, under the influence of hydrogen chloride, are cyclized to 1-aryl-1,4-dihydro-6-carbethoxy-2,7-dimethyl-4-oxopyrido[2,3-d]pyrimidines. The latter can be converted to the corresponding carboxylic and hydroxamic acids, as well as to acetylation products 1-aryl-2-acetonyl-1,4-dihydro-6-carbethoxy-7-methyl-4-oxopyrido [2,3-d]pyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 535–539, April, 1992.     

Über Heterocyclen, 12. Mitt.: Zur Bromierung der 2-Oxo-6-methyltetrahydropynimidine

Zusammenfassung Die Bromierung von 2-Oxo-6-methyl- bzw. 2-Oxo-5-carbäthoxy-6-methyltetrahydropyrimidinen verläuft unter Substitution an der CH₃-Gruppe am C-6. 2-Oxo-5-carbäthoxy-6-brommethyl-bzw.-dibrommethyltetrahydropyrimidine können in 2-Oxo-6-hydroxymethyl-tetrahydropyrimidin-5-carbonsäurelactone umgewandelt werden.Im Gegensatz zu Brom reagiert Chlor mit 2-Oxo-5-carbäthoxy-6-methyltetrahydropyrimidinen unter Addition.

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Bromine reacts with 6-methyldihydropyrimidine-2-ones or 5-carbethoxy-6-methyldihydropyrimidine-2-ones to yield 6-bromomethyldihydropyrimidine-2-ones. 5-carbethoxy-6-bromomethyldihydropyrimidine-2-ones on heating split off ethyl bromide to give 6-hydroxymethyldihydropyrimidine-2-one-5-carboxylic acid lactones.Chlorine is added to the double bond of 5-carbethoxy-6-methyldihydropyrimidine-2-ones.

     

Synthesis of 3-methyl-4-cyano-3-butenoic acid amides and their cyclization into 6-amino-2-pyridones

Two groups of amides, derivatives of 3-methyl-4-cyano- and 3-methyl-4-cyano-4-carbethoxy-3 acids were obtained from acetoacetamides in the form of mixtures of Z, E-isomers and the pure E-isomers were isolated. It was shown that amides from the first group are cyclized by bases into the corresponding 6-amino-4-methyl-2-pyridones and amides from the second group are cyclized into 6-hydroxy-5-cyano-4-methyl-2-pyridones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1636–1640, December 1992.     

Synthesis,halogenation, and nitration of 6-methyl-3-phenyl-2-pyrone derivatives

Simple methods for the synthesis of 3-aryl-6-methyl-2-pyrones and 3-aryl-5-carbalkoxy-6-methyl-2-pyrones by the reaction of ethyl -formylarylacetates with acetone and acetoacetic acid esters, respectively, are proposed. Some electrophilic substitution reactions of 6-methyl-3-phenyl-2-pyrone and 5-carbethoxy-6-methyl-3-phenyl-2-pyrone were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1477–1480, November, 1985.     

Synthesis, Structure, and Some Properties of Substituted 3-Carbethoxy(methoxy)-5-cyano-1,2,3,4-tetrahydrospirocyclohexane-4-pyridine-2-thiones

The condensation of cyclohexylidenemalononitrile or cyclohexylidenecyanoacetic ester with thioamidoethyl(methyl)malonate in the presence of sodium ethylate gave 6-amino-3-carbethoxy-5-cyano-4-spirocyclohexane-1,2,3,4-tetrahydropyridine-2-thione and 3-carbethoxy(methoxy)-5-cyano-6-oxo-4-spirocyclohexanepiperidine-2-thiones which were used in the synthesis of the corresponding substituted 2-alkylthiotetrahydropyridines. 5-Carbethoxy-3-cyano-3-methyl-6-methylthio-4-spiro-cyclohexane-3,4-dihydropyridine-2(1H)-one was studied by X-ray crystallography.     

Synthesis of 2,3-diformyl-5-ethylbenzofuran and its derivatives

A mixture of 3-formyl and 3-acetoxymethyl derivatives is formed in the oxidation of 2-carbethoxy-3-methyl-5-ethylbenzofuran with selenium dioxide. Reduction of the products with lithium aluminum hydride gives the corresponding 2,3-dihydroxymethyl derivatives, which are converted to 2,3-diformyl derivatives by successive oxidation by the Fetizon method and with manganese dioxide. The corresponding benzofuro[2, 3-d]pyridazines were synthesized by reaction of 2-carbethoxy-3-formyl-5-ethylbenzofuran with hydrazine hydrate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 893–895, July, 1982.     

Synthesis of 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carbonitriles and -6-carboxylic acid esters

Dieckmann ring closure reactions of 4-[(2-cyanoethyl)substituted amino]-2-phenyl-5-pyrimidinecarboxylates (Ha-f) afforded several 5,6,7,8-tetrahydro-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitriles (IIIa-f). The open-chain intermediates (IIa-f) were prepared by dechloroamination of 5-carbethoxy-4-chloro-2-phenylpyrimidine (1a) with several 3-substituted amino- propionitriles. Alkylation of the sodium salt of 5,6,7,8-tetrahydro-8-methyl-5-oxo-2-phenyl-pyrido[2,3-d]pyrimidine-6- carbonitrile (IIIa) with methyl iodide in DMF resulted in methylation at C-6 to afford IV. Tosylation of IIIa in pyridine gave the corresponding tosyl ester (V) of the enolic form. Oxidative dehydrogenation at the 6,7-position resulted when IIIa reacted with thionyl chloride, affording 5,8-dihydro-8-methyl-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitrile (VII). Dechloroamination of la or 5-carbethoxy-4-chloro-2-methylthiopyrimidine (Ib) with ethyl 3-ethylaminopropionate followed by Dieckmann cyclization of the resulting open-chain intermediates gave the corresponding ethyl 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylates IX'a and IX'b, respectively. These exist predominately in the enol form and undergo alkylation and oxidation reactions similar to IIIa.     

Synthesis of 1,4,5,6-tetrahydropyridine derivatives starting from trans-3-chloro-1,3-alkadien-5-ones

A method has been developed for the synthesis of 3-carbethoxy-2-methyl-6-(oxoalkylidene)-1,4,5,6-tetrahydropyridines by reaction of trans-3-chloro-1,3-alkadien-5-ones with ethyl aminocrotonate. It is shown that the corresponding vinylacetylanic ketones are intermediate products of the reactions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 497–500, April, 1987.     

Trifluoromethylfurans II

Ethyl acetoacetate reacted with 3-bromo-1,1,1-trifluoro-2-propanone in the presence of base to give 3-carbethoxy-4,5-dihydro-4-hydroxy-2-methyl-4-trifluoromethylfuran (I). Acid catalyzed dehydration of I gave the corresponding furan (III). Saponification of III gave 2-methyl-4-trifluoromethyl-3-furoic acid which was decarboxylated to yield 2-methyl-4-trifluoromethylfuran (V) for which a structure proof is presented. Conversion of the methyl groups of III and V to formyl groups is described.     

Recherches sur le benzofuranne. LXII. Orientation de la nitration de benzofurannes substitués en 2 par un groupement électro-attracteur

Nitration of 2-acetyl-, 2-carbethoxy- and 2-cyanobenzofurans by nitric acid in acetic anhydride mostly succeeds on the 5 and 6 positions, and in some instances on the 4 position and possibly on the 7 position. Moreover, in the first two cases, the substituent     

Heterocyclizations of 5-methylpyrazol-3-amine with unsaturated arylaliphatic carboxylic acid derivatives

Cyclocondensation of 5-methylpyrazol-3-amine with methyl cinnamate and arylmethylidenemalonic acids in DMF and methanol leads to the formation of 7-aryl-2-methyl-6,7-dihydropyrazolo[1,5-a]-pyrimidin-5(4H)-ones. Arylmethylidenemalonic acids react with the title amine at a ratio of 1:2 in nitrobenzene to give 4-aryl-3,5-dimethyl-1,7-dihydrodipyrazolo[3,4-b:4′,3′-e]pyridines. Heterocyclizations of 5-methylpyrazol-3-amine with 5-arylmethylidene-2,2-dimethyl-1,3-dioxane-4,6-diones or their precursors, para-substituted benzaldehydes and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum’s acid) in all solvents (methanol, DMF, and nitrobenzene) give the corresponding 4-aryl-3-methyl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones. The structure of 3-methyl-4-(4-nitrophenyl)-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-one was proved by X-ray analysis.     

Bromination,nitration, and azo coupling of substituted 3-ethoxycarbonyl-5-hydroxybenzofurans

The bromination and nitration of 2-methyl-3-ethoxycarbonyl-5-hydroxybenzofuran (I) leads to 6-bromo and 6-nitro derivatives, while azo coupling results in substitution of the hydrogen in the 4 position. The structures of the compounds obtained were confirmed by IR and PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1443–1446, November, 1971     

Synthesis of thieno[2,3-d]thia[1]pyrano[4,3-b]pyrrole derivatives

It is shown that 2-methyl-3-carbethoxy-4H,8H,5,6-dihydrothieno[2,3-d]thia[1]pyrano [4,3-b]pyrrole and 8-methyl-9-carbethoxy-10H,5,6-dihydrothieno[2,3-d]thia[1]chromeno[4,3-b]pyrrole and their S,S-dioxides, respectively, are obtained in the reaction of 2-methyl-3-carbethoxy-4-thienylhydrazine with tetrahydro-4-thiopyrone, tetrahydro-4-thiopyrone S, S-dioxide, 4-thiochromanone, and 4-thiochromanone S,S-dioxide in the presence of an acid catalyst.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 195–196, February, 1979.     

2-Bromomethyl derivatives of benzofuran and indole and their reactions with some nucleophilic reagents

The corresponding 2-bromomethyl derivatives of benzofuran and indole were obtained by bromination of 2-methyl-3-carbethoxy-5-methoxybenzofuran and 1,2-dimethyl-3-earbethoxy-5-methoxyindole with N-bromosuccinimide. A number of alkyl(aryl)thiomethyl and dialkylaminomethyl derivatives were obtained by reaction of the 2-bromomethyl derivatives with nucleophilic reagents.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 308–311, March, 1973.