Synthesis of 4-hydroxy-2-methylisocarbostyril-3-carboxanilides

A procedure for preparing the title compounds is reported. These compounds represent the first 2-substituted-4-hydroxyisocarbostyrils, a structural type which could not be obtained by N-alkylation of the previously known 2H-4-hydroxyisocarbostyril. Although 3-carboxanilides in this series could not be made by aminolysis of the corresponding 3-ester, they were successfully prepared from 4-hydroxy-2-methylisocarbostyril using aryl isocyanates and sodium hydride in hexamethylphosphoramide as solvent. Evidence is presented for an enolic (“4-hydroxy”) form of the title compounds and preference for O-alkylation was observed. Contrary to previous reports, data was obtained to support the enolic structure of the previously known 4-hydroxyisocarbostyril.     

Reaction of benzothiazol-2-one with 4-hydroxy-4-methyl-2-pentynonitrile

Reaction between the title compounds gave the unexpected 3-[5,5-dimethyl-2,5-dihydrofur-4-yl-2-(3-isopropanol-2-propenonitrile)imino]benzothiazol-2-one, as a result of the addition of two cyanoacetylene molecules.Irkutsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Irkutsk 664033. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 1003–1005, April, 1992.     

4-hydroxy-2-quinolones. 110. Bromination of 1-r-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides

1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides have been prepared. It has been shown experimentally that these compounds are brominated by molecular bromine in glacial acetic acid at position 4 of the anilide fragment. The antitubercular properties of the compounds synthesized are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1508–1516, October, 2006.     

Structure and chemistry of 4-hydroxy-6-methyl-2-pyridone

The structure of 4-hydroxy-6-methyl-2-pyridone formed by the reaction of 6-methyl-2H-pyran-2,4(3H)-dione and ammonia is characterized. A method is discussed for the structure determination of pyridone type compounds. Reaction of 4-hydroxy-6-methyl-2-pyridone with an equivalent amount of benzenesulfonyl chloride gives 4-benzenesulfonyloxy-6-methyl-2-pyridone. With two equivalent amounts of benzenesulfonyl chloride, 2,4-dibenzenesulfonyloxy-6-picoline is formed. 4-Hydroxy-6-methyl-2-pyridone is preferentially attacked by electrophiles at the 3 position.     

Reactivity and stereochemical structure of 4-hydroxy- and 4-alkoxyhexahydropyrimidine-2-thiones

Substituted 4-hydroxyhexahydropyrimidine-2-thiones were obtained by the reaction of -isothiocyanatoaldehydes with ammonia or methylamine. When heated with alcohols in the presence of p-toluenesulfonic acids, the synthesized compounds gave the corresponding 4-alkoxyhexahydropyrimidine-2-thiones, which were converted into other 4-alkoxy derivatives by the action of the respective alcohols and were hydrolyzed to the initial 4-hydroxyhexahydropyrimidine-2-thiones by the action of an aqueous solution of oxalic acid or potassium hydroxide. The reaction of the 4-hydroxyhexahydropyrimidine-2-thiones with methyl iodide led to the formation of 2-methylthio-4-hydroxy-3,4,5,6-tetrahydropyrimidine hydriodides. It was shown by PMR spectroscopy that the stereoisomers in which the hydroxyl (or alkoxyl) group has the axial orientation are thermodynamically more stable.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 260–266, February, 1985.     

3-氨基-2-羟基-4-苯基丁酸的合成

3-氨基-2-羟基-4-苯基丁酸的合成;乌苯美司;氨基羟基苯基丁酸;合成     

4-hydroxy-2-quinolones. 95. Synthesis, structure, and antitubercular properties of hetarylamides of 4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxylic acid

The optimal conditions for obtaining hetarylamides of 4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxylic acid are suggested on the basis of derivatographic investigations. The ¹H NMR spectra of the synthesized compounds, their spatial structure, and also the results of a study of their antitubercular properties are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 874–886, June, 2006.     

Synthesis of N-substituted 3-hydroxy-2-methyl-4-pyridones and -pyridonimines

Carbohydrates with 1,4 glycosidic bonds like maltose, lactose, dextrin or starch react with primary amines as well as amino acids or proteins to give i.e. 3-hydroxy-2-methyl-4-pyridones 5 and 3-hydroxy-2-methyl-4-pyridonimines 7. A generally applicable synthesis of compounds of this type is described. The pyridones 5 and pyridonimines 7 are strongly complexing agents. Molybdenum-derivatives, for instance, are suitable as fairly stable oxidation catalysts.     

4-hydroxy-2-quinolones. 109. Alkylation of 4-substituted ethyl 2-oxo-1,2-dihydro-quinoline-3-carboxylates

The alkylation of the ethyl esters of 4-methyl, 4-chloro-, and 4-amino substituted 2-oxo-1,2-dihydroquinoline-3-carboxylic acid by ethyl iodide in the system DMF/K₂CO₃ has been studied. Features of the structure of the starting compounds and their effect on the ratio of the N-and O-alkyl products formed are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1502–1507, October, 2006.     

Acetylation of 6-alkyl-5-ethoxycarbonyl-2-hydroxy-4-methyl-dihydropyrimidines and their 2-mercapto analogs

A number of 6-alkyl- and 6-aryl-5-ethoxycarbonyl-2-hydroxy-4-methyldihydropyrimidines and their 2-mercapto analogs and the acetyl derivatives of these compounds have been synthesized. In each case, two isomeric acetyl derivatives were obtained, probably the 1- and 3-acetyl compounds.     

Ring-chain isomerization of 2-substituted 3-hydroxy-3-(4-dimethyl-aminophenyl)isoindolinones

N-Unsubstituted and N-monosubstituted amides of 2-(4-dimethylaminobenzoyl)benzole acid exist in the chain form of 3-hydroxyisoindolinones in the crystalline state and in solutions in dioxane, whereas the tautomeric amide hydroxyisoindolinone equilibrium occurs (except for the methyl derivative) in more polar solvents. The analogous N-(1-adamantanyl)amide exists in the open form and does not undergo cyclization under alkaline catalysis conditions; protonation of the dimethylamino group is accompanied in all cases by splitting out of water to give compounds with a quinoid structure; an equilibrium between the protonated and quinoid forms, which is shifted markedly to favor the latter, is observed for some compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 780–785, June, 1979.     

4-hydroxy-2-quinolones. 202*. Synthesis, chemical and biological properties of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides

In continuation of the search for potential analgesics amongst 4-hydroxyquinol-2-one derivatives we have proposed and carried out a preparative method of synthesis of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides. It has been shown that bromination of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid allylamide using an equivalent of molecular bromine occurs with a conventional addition of the halogen to the allyl double bond and not with halocyclization. The results of the study of the analgesic properties of the compounds prepared are presented.     

Synthesis and biological screening of 7-hydroxy-4-methyl-2H-chromen-2-one, 7-hydroxy-4,5-dimethyl-2H-chromen-2-one and their some derivatives

7-Hydroxy-4-methyl-2H-chromen-2-one (2), 7-hydroxy-4,5-dimethyl-2H-chromen-2-one (15) and their some derivatives were synthesized for exploring selected biological screening. The compounds 9 and 13 had shown high degree of cytotoxic activity. Three compound 9, 10 and 13 showed high degree of bactericidal activity amongst the present series.     

4-Hydroxy-2-quinolones. 168*. Synthesis,chemical and antitubercular properties of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrazin-2-ylamides

1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrazin-2-ylamides have been synthesized as potential antitubercular agents. In contrast to pyrimidin-2-ylamides the compounds prepared are brominated by molecular bromine in glacial acetic acid at position 6 of the quinolone ring rather than in the amide part of the molecule. The 1-N-allyl derivative behaves similarly but undergoes halocyclization to give 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinoline-4-carboxylic acid pyrazin-2-ylamide. A comparative analysis of the antimycobacterial properties of the synthesized compounds and their isomeric pyrimidin-2-ylamides has been carried out.     

4-Hydroxy-2-quinolones 120. Synthesis and structure of ethyl 2-hydroxy-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylate

An improved method for the preparation and purification of ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]-pyrimidine-3-carboxylates is proposed. According to ¹H and ¹³C NMR spectroscopic data the synthesized compounds exist in DMSO solution in the 2-hydroxy-4-oxo form while in the crystal (at least for the case of the unsubstituted derivative) X-ray analysis shows that it occurs in the bipolar 2,4-dioxo form. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 864–876, June, 2007.     

4-Hydroxy-2-quinolones 7. Synthesis and biological properties of 1-R-3-(2-benzimidazolyl)-4-hydroxy-2-quinolones

Condensation of 1-R-3-carbethoxy-4-hydroxy-2-quinolones with o-phenylene diamine gives the corresponding 1-R-3-(2-benzimidazolyl)-4-hydroxy-2-quinolones. Data on a study of the antithyroid activity of the synthesized compounds is presented.For Communication 6, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 105–108, January, 1993.We express our sincere thanks to A. A. Kirichenko and T. S. Bozhko for the study of the antithyroid activity.     

13C NMR Analysis of some 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides

The ¹³C nmr spectra of some 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides I have been recorded and analyzed. Spectroscopic assignments were made on the basis of chemical shift theory, APT and fully coupled ¹³C nmr spectra. Spectral data support the enolic structure of these compounds.     

4-Hydroxy-2-quinolones. 152*. 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline and its biologically active derivatives

A synthesis and study of the spatial structure of 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline have been carried. 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids [1-(4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)ethylidene]hydrazides were prepared from this compound by two routes. A comparative analysis of the antitubercular properties of the synthesized compounds and of the closely structurally related N,N′-di(1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbonyl)hydrazines has been performed. *For Communication 151 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 214–222, February, 2009.     

Stereoselective synthesis of 4-hydroxy-2-phenylproline framework

Highly diastereoselective (>20:1) bromo-lactonization of N-sulfonyl-2-allyl-2-phenylglycine methyl ester (11) was observed. Successive treatment of the chiral lactone with MeONa gave the desired (2S,4R)-4-hydroxy-2-phenylproline derivative in high yield without erosion of the diastereoselectivity. The starting chiral non-racemic compound (5) was prepared from the racemic 2-phenylglycine using a classical kinetic resolution (crystallization), an asymmetric phase transfer alkylation, and an enzyme-catalyzed kinetic resolution.     

4-Hydroxy-2-quinolones. 93. Synthesis and biological properties of 2-hydroxy-4-imino-1,4-dihydroquinoline-3-carboxylic acid N-R-amides

Various methods of synthesizing amides of 2-hydroxy-4-imino-1,4-dihydroquinoline-3-carboxylic acids have been studied. Results of investigations on the antitubercular and antiinflammatory activity of the obtained compounds are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 542–555, April, 2006.