Synthesis and structure of 3-arylidene and 3-hetarylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones and their affinity toward CNS benzodiazepine receptors

The condensation of 5-aryl-7-bromo-1,2-dihydro-3H-1,4-benzodiazepin-2-ones with aromatic aldehydes gives 5-aryl-3-arylidene-and 5-aryl-7-bromo-3-hetarylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones. X-ray diffraction structural analysis yielded the molecular and crystal structures of 7-bromo-3-(4′-methoxybenzylidene)-5-phenyl-1,2-dihydro-3H-1,4-diazepin-2-one and showed that this compound has cis configuration. Radioligand analysis was used to study the affinity of these products toward central nervous system and peripheral benzodiazepine receptors. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1213–1225, August, 2007.     

Synthesis of 4-Amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones and 8H-3-R-7-Aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones

A study was carried out on the reaction of 4-amino-6-R-2,3,4,5-tetrahydro-3-thioxo-1,2,4-triazin-5-ones with halo ketones in alkaline media to yield 4-amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones, which then convert to 8H-3-R-7-aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones.     

The triflic acid-mediated cyclisation of N-benzylcinnamanilides

N-Benzylcinnamanilides cyclise with triflic acid to form 1-benzyl-4-aryl-2,4-dihydro-1H-quinolin-2-ones and 2,5-diaryl-benzazepin-3-ones. The product ratio is determined by the preferred orientation of the amide and by the electronics of the substituents. With ortho-substituted anilides, N-debenzylation also occurs to give 4-aryl-2,4-dihydro-1H-quinoline-2-ones.     

Arylmethylene derivatives of 5-R-3H-furan-2-ones and N-aryl-5-R-3H-pyrrol-2-ones in reaction with acetylacetone

Reaction with acetylacetone in the series of 3-arylmethylene-substituted furan-2-ones and pyrrol-2-ones was studied. 8-R-4-Acyl-5-aryl-3-oxo-9-oxabicyclo[4.3.0]nona-1,7-dienes and N-tolyl-8-R-4-acyl-5-aryl-3-oxo-9-azabicyclo[4.3.0]nona-1,7-dienes were synthesized. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, 1457–1462, October, 2007.     

Reactions of 4-Chloro-3-formylcoumarin with Arylhydrazines

The interaction of 3-formyl-4-coumarin with arylhydrazine hydrochlorides in the presence of sodium acetate gave the corresponding 3-arylhydrazonomethyl-4-chlorocoumarin, and with phenylhydrazine, 4-bromo- and 4-chlorophenylhydrazine hydrochlorides in the presence of two equivalents of triethylamine gave either 1-aryl- or 2-aryl[1]benzopyrano[4,3-c]pyrazol-4-ones depending on the reaction conditions. In reactions of 4-chloro-3-formylcoumarin with 2,4-dichloro-, 2,4-difluoro-, 2-hydroycarbonyl-, 4-nitro- and 3,5-di(trifluoromethyl)phenylhydrazine, 2-pyridyl- and 2-quinoxalylhydrazine in the presence of excess of triethylamine the 2-aryl[1]benzopyrano[4,3-c]pyrazol-4(2H)-ones were obtained exclusively. The structures of 1-phenyl- and 2-(2-pyridyl)[1]benzopyrano[4,3-c]pyrazolo-4(1H)ones were confirmed by X-ray crystallography. A simple method is proposed to distinguish between 1- and 2-substituted [1]benzopyrano[4,3-c]pyrazolo-4-ones on the basis of the ¹H NMR chemical shifts of the C(3)-H proton in two solvents - DMSO-d₆ and CDCl₃.     

Reactions of 4-acyl-1-alkoxyaryl-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones with nucleophilic reagents

4-Acetyl-1-alkoxyaryl-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones reacted with amines to give 1-alkoxyaryl-5-aryl-4-(1-R-aminoethylidene)pyrrolidine-2,3-diones. Reactions of amines with 4-benzoyl-substituted analogs involve nucleophilic attack on the C³ atom in the heteroring to produce the corresponding 3-R-amino-1-alkoxyaryl-5-aryl-4-benzoyl-2,5-dihydro-1H-pyrrol-2-ones. Reactions of the title compounds with hydrazine hydrate, regardless on the substituent on C₄, afforded 4-aryl-3-methyl(phenyl)-5-[2(4)-methoxyphenyl]-4,6-dihydropyrrolo[3,4-c]pyrazol-6-ones.     

CAN-promoted, diastereoselective synthesis of fused 2,3-dihydrofurans and their transformation into tetrahydroindoles

The reaction between 1,3-cyclohexanediones and chalcones (or their vinilogs) in the presence of 2.5 equiv of cerium(IV) ammonium nitrate afforded trans-2-arylcarbonyl-3-aryl (or styryl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-ones in good to excellent yields and in high diastereoselectivities. The method was also extended to the preparation of derivatives of the 5,6-dihydro-2H-cyclopenta[b]furan-4(3H)-one system. The fused 2,3-dihydrofuran derivatives were transformed into 1-alkyl-2-acyl-3-aryl-6,7-dihydroindole-4(5H)-ones by 2,3-dehydrogenation followed by reaction with primary amines. The direct reaction of the tetrahydrobenzofuran-4(5H)-one compounds derived from dimedone with amines gave 1-alkyl-2-alkylimino-3-aryl-6,7-dihydroindole-4(5H)-ones, while starting materials derived from 1,3-cyclohexanedione underwent an unprecedented 2-deacylation reaction and gave 1-alkyl-3-aryl-6,7-dihydroindole-4(5H)-ones.     

Asymmetric induction in the reactions of 3-aryl-1,2,4-triazin-5(4H)-ones with C-nucleophiles

3-Aryl-1,2,4-triazin-5(4H)-ones, in the presence of N-protected amino acids, react with C-nucleophiles to form 1-acyl-6-Nu-3-aryl-1,6-dihydro-1,2,4-triazin-5(4H)-ones in high diastereomeric excess. This is the first case of the use of amino acids as chiral auxiliaries in nucleophilic additions to triazinones.     

Cyclocondensation between fatty acid hydrazides and 1,1,1-trifluoro-4-alkoxy-3-alken-2-ones: Introducing a trifluoromethylated head onto fatty acid moieties

This paper reports the regioselective synthesis of new trifluoromethylated lipid derivatives, namely, 1-(5-hydroxy-5-trifluoromethyl-3-alkyl-4,5-dihydro-1H-pyrazol-1-yl)alkan-1-ones, through cyclocondensation reactions between a series of fatty hydrazides (palmitoyl, stearoyl, and oleoyl hydrazides) obtained from fatty acids from renewable resources (1,1,1-trifluoro-4-alkoxy-3-alken-2-ones [F₃CC(O)CH?C(R¹)OR, where R¹?=?H and R?Et; R¹?=?–(CH₂)₆CH₃, –(CH₂)₆CH₃, –(CH₂)₈CH₃, –(CH₂)₉CH₃, –(CH₂)₁₀CH₃, –(CH₂)₁₂CH₃, –(CH₂)₂Ph], and R?Me). Experimental observations showed that the lipophilic characteristic of 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-pyrazoles (5–7) prevent the acid catalyzed dehydration to aromatization of 1H-pyrazole ring, although in some cyclocondensations a proportion of the aromatic derivative 1-(5-trifluoromethyl-3-alkyl-1H-pyrazol-1-yl)alkan-1-one was obtained. All products were characterized using multinuclear (¹H, ¹³C, ¹⁹F) NMR spectroscopy.     

1-Aryl-1-chloro-2,2,2-trifluoroethylisocyanates—convenient reagents for synthesis of 2-aryl-2-trifluoromethyl-2,3-dihydro-4H-benzo[e][1,3]oxazin-4-ones

1-Aryl-1-chloro-2,2,2-trifluoroethylisocyanates react with 3-alkoxyphenols to form N-(1-aryl-2,2,2-trifluoroethylidene)-O-(3-alkoxyphenyl)urethanes, which undergo intramolecular thermal cyclization into derivatives of 2-aryl-2-trifluoromethyl-2,3-dihydro-4H-benzo[e][1,3]oxazin-4-ones.     

Aminolysis of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>]1,3]thiazin-7-ones

We have established that the products of aminolysis of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo-[5,1-b][1,3]thiazin-7-ones in boiling ethanol are 3-R-3-(5-aryl-4H-1,2,4-triazol-3-ylsulfanyl)-propanamides, and at 180°C–210°C (depending on the structure of the substituent R): 3-phenyl-4,5-dihydro-1H-1,2,4-triazoline-5-thione and 3-arylacrylamides or 3-(3-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)propanamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1587–1592, October, 2005.     

Three-Component Condensation of Methyl Acylpyruvates with Aromatic Aldehydes and Ethylenediamine. Chemical Properties of the Products

Reactions of methyl acetyl- or benzoylpyruvates with aromatic aldehydes and ethylenediamine, depending on the reactant ratio, afforded 4-acyl-1-(2-aminoethyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones or 1,2-bis(4-acyl-5-aryl-3-hydroxy-2-oxo-2,5-dihydro-1H-pyrrol-1-yl)ethanes. Substituted 1-(2-aminoethyl)-3-hydroxy-2,5-dihydro-1H-pyrrol-2-one hydrochlorides were brought into reactions with p-methoxyaniline and hydrazine.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 2, 2005, pp. 282–287.Original Russian Text Copyright © 2005 by Gein, Kasimova.     

Three-component reaction of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with aromatic aldehydes and propane-1,2-diamine and chemical properties of the products

The reactions of methyl 2,4-dioxo-4-phenylbutanoate and methyl 2,4-dioxopentanoate with a mixture of an aromatic aldehyde and propane-1,2-diamine, depending on the initial reactant ratio, gave 4-acyl-1-(2-aminopropyl)-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones and 1,1′-(propane-1,2-diyl)bis(4-acetyl-3-hydroxy-5-phenyl-2,5-dihydro-1H-pyrrol-2-one). Reactions of substituted 1-(2-aminopropyl)-2,5-dihydro-1H-pyrrol-2-ones with aromatic amines and hydrazines were studied, and the structure of one of the products, 5-(2-aminopropyl)-3,4-diphenylpyrrolo[3,4-c]pyrazol-6-one, was proved by X-ray analysis.     

The synthesis of 5-acyl-4-aryl(alkyl)-2-aryl-1,2,3-triazole 1-oxides by lead tetraacetate oxidation of mono- and bisarylhydrazones of α-hydroxyimino-β-diketones

The synthesis and lead tetraacetate oxidation of the title mono- and bis-arylhydrazones to the corresponding 5-acyl-4-aryl(alkyl)-2-aryl-1,2,3-triazole 1-oxides is described.     

Effective synthesis of 5-aryl-3-ethylidene-3H-pyrrol-2-ones

Substituted 5-aryl-3-ethylidene-3H-pyrrol-2-ones were synthesized by the reaction of the corresponding 4-aryl-4-oxobutanoic acids with ketones in the presence of aminating agents. The conditions of this reaction were developed with the use of both the conventional condensation technique and microwave activation. The structures of the reaction products were con-firmed by elemental analysis, IR spectroscopy, and ¹H NMR spectroscopy. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 693–696, April, 2006.     

Cycloacylation of <Emphasis Type="Italic">N</Emphasis>-Phenyl-3-oxobutanethioamide with 3-Aryl-2-propenoyl Chlorides

Reactions of N-phenyl-3-oxobutanethioamide with 3-aryl-2-propenoyl chlorides in acetone in the presence of potassium carbonate give rise to 4-aryl-5-acetyl-1-phenyl-6-thioxopiperidin-2-ones, 2-aryl-5-acetyl-6-phenylamino-2,3-dihydro-4H-thiopyran-4-ones, and 6-aryl-2-acetonylidene-3-phenyl-5,6-dihydro-4H-1,3-thiazin-4-ones whose structure was proved both by spectral methods and chemical transformations.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 2, 2005, pp. 292–296.Original Russian Text Copyright © 2005 by Britsun, Borisevich, Samoilenko, Lozinskii.     

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.     

2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones

A novel method for synthesis of 2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 3-R-4,5-dihydro-1H-1,2,4-triazole-5-thiones with 3-aryl(heteryl)-2-propenoyl chlorides is proposed.     

Reaction of 1-Aryl-3-methylpyrazol-5-ones with 2-Cyanoaryldiazonium Bisulfates

2-Cyanoaryldiazonium bisulfates, obtained by the action of nitrosyl sulfuric acid on isatin 3-hydrazone and its 5-bromo and 5-nitro derivatives, couple with 1-aryl-3-methylpyrazol-5-ones and form 4-arylhydrazones of 1-aryl-3-methylpyrazole-4,5-diones. It was established on the basis of data of IR, UV, and ¹H NMR spectra and of X-ray structural analysis that the coupling products exist in the hydrazone form stabilized by an intramolecular hydrogen bond.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 210–215, February, 2005.     

Reaction of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazin-7-ones with Aryl Bromomethyl Ketones and Benzyl Bromide

The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles and 3-phenyl-2-propenoic acid, depending on the structure of R. The reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with benzyl bromide yields 5-aryl-3-benzylthio-4H-1,2,4-triazoles and 3-aryl-2-propenoyl bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 905–909, June, 2005.