Chemoselective reduction of 3-arylmethylidenetetrahydrofuran-2,4-diones with triethylsilane and sodium cyanotrihydridoborate in acid media

3-Arylmethylidenetetrahydrofuran-2,4-diones were smoothly reduced to the corresponding 3-benzyl derivatives in 50–98% yield with triethylsilane in trifluoroacetic acid or with sodium cyanotrihydridoborate in the system tetrahydrofuran-2 N hydrochloric acid. The reduction of 3-(3-arylprop-2-en-1-ylidene)-tetrahydrofuran-2,4-diones with sodium cyanotrihydridoborate gave 3-cinnamyltetrahydrofuran-2,4-diones as the only products.     

Efficient solid-phase synthesis of quinazoline-2,4-diones with various substituents on aromatic rings

We have developed a method for the solid-phase synthesis of quinazoline-2,4-diones with various substituents on the aromatic ring. Although there have been numerous reports of the solid-phase synthesis of quinazoline-2,4-diones, they were not applicable to the synthesis of the quinazoline-2,4-diones with electron-withdrawing substituents on the aromatic ring. Considering the poor nucleophilicity of the amino group of anthranilic acids, coupling of anthranilic acids to solid-supported amines was investigated without protecting the amino group. Various anthranilamides were prepared using anthranilic acids with electron-withdrawing substituents because a wide range of anthranilic acids are commercially available. These anthranilamides were successfully cyclized with carbonyldiimidazole to give quinazoline-2,4-diones with high purity.     

Synthesis of 4-[Alkylsulfanyl(sulfonyl)methyl]isoxazoles and -1<Emphasis Type="Italic">H</Emphasis>-pyrazoles from 3-[(Alkylsulfanyl)methyl]- pentane-2,4-diones

New 4-[(alkylsulfanyl)methyl]- and 4-[(alkanesulfonyl)methyl]isoxazoles and -1H-pyrazoles were synthesized by reactions of 3-[(alkylsulfanyl)methyl]- and 3-[(alkanesulfonyl)methyl]pentane-2,4-diones with hydroxylamine and hydrazine, phenylhydrazine, semicarbazide, or thiosemicarbazide, respectively. The heterocyclization of 3-[(alkylsulfanyl)methyl]pentane-2,4-diones with thiosemicarbazide and semicarbazide hydrochloride was accompanied by elimination of amide or thioamide group. 3-[(Alkanesulfonyl)methyl]pentane- 2,4-diones were found to exist in solution as enol tautomers; they were prepared by oxidation of the corresponding 3-[(alkylsulfanyl)methyl]pentane-2,4-diones with hydrogen peroxide in acetic acid in the presence of a catalytic amount of sulfuric acid.     

Synthesis of 6-Aroyl-3,3,5,5-tetramethyl-2,3,5,6-tetrahydropyran-2,4-diones and Their Reaction with Phenylhydrazine

Methyl 4-bromo-3-oxo-2,2,4-trimethylpentanoate reacts with zinc and arylglyoxals yielding 6-aroyl-3,3,5,5-tetramethyl-2,3,5,6-tetrahydropyran-2,4-diones. The latter with phenylhydrazine afford 6-(1-aryl-2-phenylhydrazonomethyl)-3,3,5,5-tetramethyl-2,3,5,6-tetrahydropyran-2,4-diones.     

1,3,4,6-Tetracarbonyl Compounds: VI. Synthesis of 2-Substituted 6-Aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic Acid Esters and Amides

The Knoevenagel reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with ethyl cyanoacetate or malonodinitrile yields 2-substituted 6-aryl-3,4-dihydroxy-6-oxo-2,4-hexadienoic acid esters or amides which exhibit biological activity. The structure of the products is discussed, taking into account the structure of known 3,4-dihydroxy-6-oxo-2,4-hexadienoic acid esters and 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones.     

Quinazolines 1. Synthesis and chemical reactions of 6-chlorosulfonyl-quinazoline-2,4-diones

Treatment of quinazoline-2,4-dione and its symmetrical 1,3-dialkyl derivatives with chlorosulfonic acid gave the corresponding 6-chlorosulfonylquinazoline-2,4-diones. Reaction of the compounds obtained with nucleophilic agents (water, ammonia, aliphatic and cyclic amines) gave the corresponding free 2,4-dioxoquinazoline-6-sulfonic acids, 6-sulfamidoquinazoline-2,4-diones, and 2,4-dioxoquinazoline-6-sulfonic acid amides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 420–427, March 2008.     

Reaction of 3-aminoquinoline-2,4-diones with nitrourea. Synthetic route to novel 3-ureidoquinoline-2,4-diones and imidazo[4,5-c]quinoline-2,4-diones

1-Unsubstituted 3-alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with 1-substituted and 1,1-disubstituted ureas in boiling acetic acid to give 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones. In contrast, the reaction of these amines with nitrourea in dioxane affords novel 3-alkyl/aryl-3-ureido-1H,3H-quinoline-2,4-diones or 9b-hydroxy-3a-alkyl/aryl-3,3a,5,9b-tetrahydro-1H-imidazo[4,5-c]quinoline-2,4-diones, which can smoothly be dehydrated to 3a-alkyl/aryl-3,3a-dihydro-5H-imidazo[4,5-c]quinoline-2,4-diones. All three types of products can be converted to 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones by refluxing in acetic acid.     

Annelation of 3,4-dihydroisoquinolines by 3-acyl-5,5-dimethylthiopyran-2,4-diones. Synthesis and properties of 8-aza-17-thia-d-homogona-12,17a-diones

We have used annelation of 3,4-dihydroisoquinolines by 3-acyl-5,5-dimethylthiopyran-2,4-diones to obtain the corresponding 8-aza-17-thia-D-homogonanes, which are novel representatives of heterosteroids. We have studied the tautomerism of 3-acylthiopyran-2,4-diones using NMR spectroscopy and H/D-isotope exchange. We have obtained 2H-isotopomers of 3-acylthiopyran-2,4-diones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1572–1583, October, 2004.     

Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the reaction products

The reaction of tertiary α-chloroketones with ethanolamine has not been hitherto described in the literature. Herein, we describe the reaction of tertiary 3-chloroquinoline-2,4-diones with ethanolamine to give novel 3-(2-hydroxyethylamino)quinoline-2,4-diones. These compounds provide 3-(2-oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-diones and new compounds with dimeric character after reaction with triphosgene. Molecular rearrangement proceeds during the reaction of 3-(2-hydroxyethylamino)quinoline-2,4-diones with isocyanic acid. Three types of reaction products arise: 2-(2-hydroxyethyl)imidazo[1,5-c]quinazoline-3,5-diones, 3-(2-hydroxyethyl)-3,3a-dihydro-2H-imidazo[4,5-]quinoline-4(5H)diones and primarily 5-hydroxy-1-(hydroxyethyl)-1′H-spiro[imidazolidine-5,3′-indole]-2,2′-diones. The reaction mechanism and product stereochemistry are discussed. The ¹H, ¹³C and ¹⁵N NMR spectra of the prepared compounds were measured, and all resonances were assigned from appropriate two-dimensional experiments.     

Synthesis of 1,3-dialkylpyrazolo [1,5-a]-1,3,5-triazine-2,4-diones isomers of 1,3-dialkylxanthines

The synthesis of a new series of alkylxanthine analogs containing a bridgehead nitrogen atom is reported. 1,3-Dialkylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones, were prepared by the treatment of 3-methylpyrazolo[1,5-a]-1,3,5-triazine-2,4-dione (3) with the corresponding alkyl iodide. Similarly, the reaction of 3-methyl-7-phenylpyrazolo[1,5-a]-1,3,5-dialkyl-7-phenylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones. The starting materials, 3 and 17 , were prepared via the reaction of an appropriate 3-aminopyrazole with ethoxycarbonyl isothiocyanate. Several 8-bromo derivatives were prepared by direct bromination of the 1,3-dialkylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones.     

Versatile synthesis of quaternary 1,3-oxazolidine-2,4-diones and their use in the preparation of α-hydroxyamides

A new approach to the synthesis of 1,3-oxazolidine-2,4-diones, via a two-step reaction sequence, starting from the readily available α-ketols and isocyanates, is reported. The condensation of the latter led to the key precursors 4-methylene-2-oxazolidinones, which are converted into the diones by an oxidative cleavage of the exocyclic double bond. Thus, 5,5-disubstituted 1,3-oxazolidine-2,4-diones can be accessed in good yields from the appropriate functionalized α-ketols. Moreover, two alternative routes are also described either by functionalization of 4-oxazolin-2-ones or by alkylation of the 1,3-oxazolidine-2,4-dione core previously prepared. Upon hydrolysis of the 1,3-oxazolidine-2,4-diones, a series of α-hydroxyamides bearing a quaternary stereocenter were obtained.     

Stereocontrolled synthesis of 2,4-diamino-3-hydroxyacids starting from diketopiperazines: a new route for the preparation of statine analogues

Chiral 3-aminopyrrolidine-2,4-diones, obtained by transannular rearrangement of activated diketopiperazines, could be a springboard toward an exceptional stereoselective synthesis of original 2-disubstituted statines. After a selective reduction of the pyrrolidine-2,4-diones, the access to opened 2,4-diamino-3-hydroxyacid esters was carried out by a subsequent alkaline treatment or directly through a tandem reduction-solvolysis.     

Rearrangement of 5-phenylthiazolidine-2,4-diones to chiral α-ketoamides via α-elimination

An unexpected reaction took place when 5-phenylthiazolidine-2,4-diones were treated in basic media to produce phenyl-α-ketoamides in good yields. The 5-phenylthiazolidine-2,4-diones used as reactants were achieved through a rearrangement, which took place in the corresponding N-acyloxazolidinethiones.     

1,3,4,6-Tetracarbonyl Compounds: IV. Reaction of 3,4-Dihydroxy-2,4-hexadiene-1,6-diones with Hydrazine and Arylhydrazines

Reactions of 1,6-disubstituted 3,4-dihydroxy-2,4-hexadiene-1,6-diones with hydrazine hydrate or hydrochloride afforded heterocyclization products, 3,3'-bipyrazoles. The chemoselective reaction of 1,6-diaryl-3,4-dihydroxy-2,4-hexadiene-1,6-diones with arylhydrazines gave rise to 1,1',5,5'-tetraaryl-3,3'-bipyrazoles and 1,5-diaryl-3-aroylacetylpyrazoles. The specific structural features of the pyrazole derivatives obtained are discussed. Some pyrazoles show bacteriostatic and antileukemic activity.     

Reactions of selenium dichloride and dibromide with divinyl sulfone: synthesis of novel four- and five-membered selenium heterocycles

The reactions of selenium dichloride and dibromide with divinyl sulfone leading to novel selenium heterocycles, 2,4-bis(halomethyl)-1,3-thiaselenetane-1,1-diones and 5-halo-2-halomethyl-1,3-thiaselenolane-1,1-diones, have been studied. Under the action of silica gel or pyridine, 5-halo-2-halomethyl-1,3-thiaselenolane-1,1-diones undergo facile regioselective dehydrohalogenation into 5-halo-2-methylene-1,3-thiaselenolane-1,1-diones.     

Coupling of pentacarbonyl[(cyclopropyl)methoxymethylene]molybdenum complex with ferrocenyl alkynes: Synthesis of ferrocenyl-substituted cycloheptadienones and cycloheptenediones

Pentacarbonyl[(cyclopropyl)methoxymethylene]molybdenum complex reacts with ferrocenyl alkynes to afford ferrocenyl-substituted 2,4-cycloheptadienones as major products, accompanied by varying amounts of 2-cycloheptene-1,4-diones and/or 2-cyclobutenones. 2-Cycloheptene-1,4-diones are secondary reaction products and result from initially formed 2,4-cycloheptadienones via hydrolysis. In one reaction, a hydroxy-substituted 2,4-cycloheptadienone derivative was isolated, which was not observed previously from similar reactions.     

Conventional and microwave-assisted conversion of substituted 3-amino-oxazolidin-2,4-diones into N',N'-disubstituted alpha-hydroxyhydrazides

Substituted 3-amino-oxazolidin-2,4-diones have been prepared by reacting cyanohydrins or alpha-hydroxyesters subsequently with 1,1'-carbonyldiimidazole and 1,1-disubstituted hydrazines followed by acidic hydrolysis in case of the intermediate 3-amino-4-imino-oxazolidin-2-ones. Conventional and microwave-assisted syntheses of N',N'-disubstituted alpha-hydroxyhydrazides have been accomplished by reacting substituted 3-amino-oxazolidin-2,4-diones with catalytic amounts of sodium methoxide in methanol.     

Five-membered 2,3-dioxoheterocycles. 10. Reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with N-substituted ureas and their thio and seleno analogs

3-Aryl-5-phenacylideneimidazolidine-2,4-diones, 3-aryl-5-phenacylidene-4-oxoimidazolidine-2-thiones, and 5-phenacylidene-4-oxoimidazolidine-2-selenones were obtained from 5-aryl-2,3-dihydrofuran-2,3-diones and arylureas, arylthioureas, and selenoureas respectively in glacial acetic acid. In the reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with cyanoguanidine in 98% acetic acid 5-phenacylideneimidazolidine-2,4-diones were isolated, and in anhydrous acetic acid 2-imino-3-amidino-5-phenacylidene-4-oxazolidones were isolated. When heated in a water-dioxane solution of hydrochloric acid, the latter are converted into 5-phenacylideneimidazolidine-2, 4-diones.For Communication 9, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1411–1413, October, 1988.     

Conversion of 3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-diones to 2,3a,4,5-tetrahydrofuro[2,3-c]quinoline-2,4-diones via an intramolecular wittig reaction

The preparation of 2,3a,4,5-tetrahydrofuro[2,3-c]quinoline-2,4-diones starting from 3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-diones and using the reaction path via bromoacetylderivatives and triphenylphosphonioacetyl derivatives of the initial substances is described. The nmr spectra of the products are discussed.     

Synthesis and keto-enol tautomerism of 6-alkyl-1-alkoxypyridine-2,4-diones

Reactions of 2,2-dimethyl-5-(3-oxoalkanoyl)-1,3-dioxane-4,6-diones with alkoxyamines proceed regioselectively at the β′-keto group of the side acyl chain affording the corresponding tricarbonyl imines whose boiling in toluene leads to the formation of products of intramolecular cyclization, N-alkoxy-2,4-dioxopyridine-3-carboxylic acids. The decarboxylition of the obtained pyridine-3-carboxylic acids in mesitylene at 160–165°C gives in the preparative yield N-alkoxypyridine-2,4-diones. Proceeding from the IR and NMR spectra the problems of the keto-enol and imine-enamine tautomerism were discussed for the series of 5-acyl derivatives of the Meldrum acid and the obtained N-alkoxypyridine-2,4-diones.