SYNTHESIS AND REACTIONS OF 2,3-DIHYDRO- 5-ARYL-5H,6H-THIAZOLO[3,2-b]-2,4-DIAZAFLUORENE-3,6-DIONES OF POTENTIAL BIOLOGICAL ACTIVITIES

Abstract

1,2,3,4-Tetrahydro-l-aryl-3,9-dioxo-2,4-diazafluorenes (2) and 1,2,3,4-tetrahydro-1-aryl-9-oxo-3-thi-oxo-2,4-diazafluorenes (3) were newly synthesized. Compounds 3 reacted with chloroacetic acid, α-bromopropanoic acid, or B-bromopropanoic acid in the presence of fused sodium acetate and acetic anhydride to give 2,3-dihydro-5-aryl-5H,6H-thiazolo[3,2-b]2,4-diazafluorene-3,6-diones (4), 2-methyl-2,3-dihydro-5-aryl-5H,6H-thiazolo[3,2-b]2,4-diazafluorene-3,6-diones (5) and 2,3-dihydro-6-aryl-6H,7H-thiazino[3,2-b]2,4-diazafluorene-4,7-diones (6), respectively.

2,3-Dihydro-2-arylmethylene-5-aryl-5H,6H-thiazolo[3,2-b]2,4-diazafluorene-3,6-diones (7) were prepared by the reaction of compounds (3) with chloroacetic acid and aromatic aldehydes in the presence of fused sodium acetate and acetic anhydride or by the reactions of (4) with aromatic aldehydes in the presence of acetic anhydride.

2-(Arylhydroazono)-5-aryl-2,3-dihydro-5H,6H-thiazolo[3,2-b]2,4-diazafluorene-3,6-diones (8) were synthesized by coupling (4) with aryldiazonium salts in the presence of pyridine.     

Five-membered 2,3-dioxoheterocycles

The reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with benzamide oxime, diaminoglyoxime, and hydroxyurea gave 3-phenyl-5-aroylacetyl-1,2,4-oxadiazoles, 5,6-dihydroxyimino-3-phenacylidenepiperazin-2-ones, and 3-hydroxy-5-phenacylideneimidazolidine-2,4-diones, respectively. 6-Phenacylidene-5-oxo-4,5,6,7-tetrahydrofurazano [3,4-b]pyrazines are formed in the reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with diaminofurazan.For Communication 7, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1457–1460, November, 1988.     

Huisgen reaction of nitrile oxides and nitrile imines leading to isoxazoline and pyrazole-4,6-diones

Huisgen reaction of nitrile oxides and nitrile imines generated in situ in the presence of N-benzylmaleimide afforded regiospecifically the corresponding cis-3-aryl-5-benzyl-3a,4,6,6atetrahydro-4H, 6H-pyrrolo[3,4-d]isoxazoline-4,6-diones and cis-3-aryl-5-benzyl-1-(2′,4′-dibromophenyl)-3a, 4,6,6a-tetrahydro-1H,5H-pyrrolo[3,4-c]pyrazole-4,6-diones in good yield. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 935–939, June, 2006.     

Synthesis of spiro- and dispirotetrahydropyrane-2,4-diones involving cyclobutane fragment in position 5 of heterocycle

Methyl 3-(1-bromocyclobutyl)-2,2-dimethyl-3-oxopropanoates, 1-(1-bromocyclobutyl-carbonyl) cyclopentanoates and 1-(1-bromocyclobutylcarbonyl)cyclobutanoates react with zinc and aromatic aldehydes to form 5-aryl-8,8-dimethyl-6-oxaspiro[3.5]nonane-7,9-diones, 13-aryl-12-oxadispiro[3.1.4.3]tridecane-5,11-diones and 12-aryl-11-oxadispiro[3.1.3.3]dodecane-5,10-diones respectively.     

3-methylthio-1,2-dithiolylium salts : Reaction with 4-hydroxy-6-methyl-2H-pyran-2-one and 4-hydroxycoumarin

The reaction of 4- and 5-aryl-3-methylthio-1,2-dithiolylium iodides with 4-hydroxy-6-methyl-2$\text{H}$-pyran-2-one and 4-hydroxycoumarin has been studied. 4-Substituted salts yielded 3-aryl-7-methyl-2-thioxo-2$\text{H}$,5$\text{H}$-pyrano [3,2-c]pyran-5-ones and 3-aryl-2-thioxo-2H,5H-pyrano[3,2-c]benzo[e]pyran-5-ones, respectively, whereas 5-substituted salts gave rise to 3-(5′-aryl-1′,2′-dithiol-3′-ylidene)-6-methyl-2$\text{H}$-pyran-2,4-diones and 3-(5′-aryl-1′,2′-dithiol-3′-ylidene)-2$\text{H}$-benzo [b]-pyran-2,4-diones.     

Reactions of 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones with arylamines and hydrazine hydrate

Depending on the reaction condition, 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones reacted with aromatic amines to yield 3-arylamino-3-pyrrolin-2-ones or 4-[aryl (arylamino) methylene]tetrahydropyrrole-2,3-diones. Reactions of 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones with hydrazine hydrate afforded pyrrolo[3,4-c]pyrazol-6-ones.     

Five-Membered 2,3-Dioxo Heterocycles: XLV. Thermolysis of 5-Aryl-4-phenyl-2,3-dihydrofuran-2,3-diones in the Absence of Other Partners and in the Presence of Carbonyl Compounds

Aroyl(phenyl)ketenes generated by thermolysis of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones undergo [4+2]-cyclodimerization to 3-aroyl-6-aryl-3,5-diphenyl-3,4-dihydro-2H-pyran-2,4-diones. Heating of the latter leads to rearrangement with formation of 4-aroyloxy-6-aryl-3,5-diphenyl-2H-pyran-2-ones. Thermolysis of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones in the presence of carbonyl compounds yields 6-aryl-5-phenyl-4H-1,3-dioxin-4-ones.     

Studies on the syntheses of heterocycles from 3-arylsydnone-4-carbohydroximic acid chlorides with N-arylmaleimides, [1,4]naphthoquinone and aromatic amines

3-Arylsydnone-4-carbohydroximic acid chlorides (1) could react with N-arylmaleimides (3a–b) or 2-methyl-N-phenylmale-imide (3c) to give 3-(3-arylsydnon-4-yl)-5-aryl-3a,6a-dihydro-pyrrolo[3,4-d]isoxazole-4,6-diones (4a–h) or 6a-methyl-3-(3-arylsydnon-4-yl)-5-phenyl-3a,6a-dihydro-pyrrolo[3,4-d]isoxazole-4,6-diones (4i–l), respectively. However, 3-(arylsydnon-4-yl)-naphtho[2,3-d]isoxazole-4,9-diones (6a–d) were obtained in good yield by the reaction of carbohydroximic acid chlorides 1 with [1,4]naphthoquinone. Furthermore, 2-(3-arylsydnon-4-yl)benzoxazoles (9a–d) and 2-(3-arylsydnon-4-yl)benzothiazoles (9e–h) were obtained via the reaction of carbohydroximic acid chlorides 1 with ortho-substituted aromatic amines 7a and b.     

Reactions of bromine-containing organozinc compounds derived from α,α-dibromo ketones with 2-arylmethylideneindan-1,3-diones and 5-arylmethylidene-2,2-dimethyl-1,3-dioxane-4,6-diones

Bromine-containing organozinc compounds generated from 1,1-dibromo-3,3-dimethylbutan-2-one reacted with 2-arylmethylideneindan-1,3-diones and 5-arylmethylidene-2,2-dimethyl-1,3-dioxane-4,6-diones to give 3-aryl-2-(2,2-dimethylpropanoyl)spiro[cyclopropane-1,2′-indan]-1′,3′-diones and 1-aryl-6,6-dimethyl-2-(2,2-dimethylpropanoyl)-5,7-dioxaspiro[2.5]octan-4,8-diones, respectively. Reactions of 2-arylmethylideneindan-1,3-diones with bromine-containing zinc enolates derived from 1-aryl-2,2-dibromopropan-1-ones and 2,2-dibromo-1,2,3,4-tetrahydronaphthalen-1-one resulted in the formation of 2-aroyl-3-aryl-2-methylspiro-[cyclopropane-1,2′-indan]-1′,3′-diones and 2,3: 8,9-dibenzo-12-phenyldispiro[4.0.5.1]dodecane-1,4,7-trione, respectively.     

Heterocyclization of functionalized heterocumulenes with C,N-, C,O-, and C,S-binucleophiles: VIII. Synthesis of pyrano(chromeno)[3,4-e][1,3]oxazines by condensation of 1-chloroalkyl isocyanates with 4-hydroxy-6-methylpyran-2-one and 4-hydroxycoumarin

1-Chlorobenzyl isocyanates react with 4-hydroxy-6-methylpyran-2-one and 4-hydroxycoumarin forming 4-aryl-3,4-dihydro-2H,5H-pyrano(chromeno)[3,4-e][1,3]oxazine-2,5-diones. The reaction of 1-aryl-2,2,2-trifluoro-1-chloroethyl isocyanates with the above substrates gives rise to structurally isomeric 2-aryl-2-trifluoromethyl-2,3-dihydro-2H,5H-pyrano(chromeno)[3,4-e][1,3]-oxazine-4,5-diones.     

Reactions of Substituted 2,3,7-Triazabicyclo[3.3.0]oct-2-enes and 1,2,7-Triazaspiro[4.4]non-1-enes with Halogens

Halogenation of 1-substituted 7-aryl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-diones gives different products, depending on the substituent in position 1 (R¹): when R¹ = Ar, 6-chloro-3-azabicyclo[3.1.0]hexanes are formed, while compounds with R¹ = H or Me give rise to 2- or 4-chloro-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-diones whose thermolysis leads to formation of the corresponding 6-chloro-3-azabicyclo[3.1.0]hexanes. Chlorination of 7-aryl-1,2,7-triazaspiro[4.4]non-1-ene-6,8-diones yields 3-chloro-1,2,7-triazaspiro[4.4]non-1-ene-6,8-diones, and thermolysis of the latter affords 1-chloro-5-azaspiro[2.4]heptanes.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 78–88.Original Russian Text Copyright © 2005 by Molchanov, Stepakov, Kostikov.     

Synthesis of 8-R-9c-alkyl-1-aryl-2-benzyl-1-hydroxy-1,2,9b,9c-tetrahydro-5-oxa-2-aza-cyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones and reaction thereof with acetic anhydride

The reaction of zinc enolates synthesized from 1-aryl-2,2-dibromoalkanones and zinc with 6-R-2-oxochromene-3-carboxylic acid N-benzylamide affords 8-R-9c-alkyl-1-aryl-2-benzyl-1-hydroxy-1,2,9b,9c-tetrahydro-5-oxa-2-aza-cyclopenta[2,3]cyclopropa[1,2-a]naphthalene-3,4-diones. Acylation of these compounds is accompanied by an unexpected rearrangement producing a sole geometrical isomer of 4′-alkyl-5′-aryl-1′-benzyl-3,4,2′,3′-tetrahydro-2,2′-dioxospiro[chroman-3,3′-pyrrol]-4-yl acetates.     

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.     

Synthesis of 6-substituted 7-aryl-5,6-dihydropyrido[2,3-d]pyrimidine(1H,3H)-2,4-diones using the Vilsmeier reaction

The reaction of 6-amino-1,3-dimethyluracil with equimolar amounts of arylalkanone Mannich bases under optimized reaction conditions leads to 7-aryl-5,6-dihydropyrido[2,3-d]pyrimidines in a yield of 50-80%. Functionalization of these dihydropyridopyrimidine(1H,3H)-2,4-diones with the Vilsmeier reagent affords, depending on the reaction conditions, either 6-dimethylaminomethylidene substituted 5H-pyrido[2,3-d]pyrimidine(1H,3H)-2,4-diones or the corresponding pyridopyrimidine(1H,3H)-2,4-diones bearing a carboxaldehyde function in position 6 of the heterocycle. Some further transformations of the aldehyde function demonstrate the synthetic potential of the synthesized structures, introducing pharmacologically relevant basic substituents into the side chain of these pyrido[2,3-d]pyrimidine derivatives.     

Syntheses based on 8-substituted 3-bromoacetyl-3,8-dimethyl-2,7-dioxaspiro[4,4]nonane-1,6-diones

By reaction of 8-substituted 3-bromoacetyl-3,8-dimethyl-2,7-dioxaspiro[4,4]nonane-1,6-diones with thiourea and substituted thioureas under Hansch reaction conditions, we have obtained the novel heterocycles 3-[2′-amino(arylamino)thiazol-4-yl]-3,8-dimethyl-2,7-dioxaspiro[4,4]nonane-1,6-diones. By reacting the above-indicated bromoacetyl spirodilactones with 5-aryl-3-mercapto-1,2,4-triazoles, we obtained 8-substituted 3-(aryl-3,8-dimethyl-1′,2′,4′-triazol-3′-yl)thioacetyl-2,7-dioxaspiro[4,4]nonane-1,6-diones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 123–129, January, 2006.     

Synthesis of 6-arylspiro[tetrahydropyran-3,1′-cyclobutane]-2,4-diones

Methyl 1-(2-bromo-2-methyl-1-oxopropyl)-, 1-(1-bromocyclopentylcarbonyl)-, and 1-(1-bromocyclohexylcarbonyl) cyclobutanecarboxylates reacted with zinc and aromatic aldehydes to give, respectively, 7-aryl-2,2-dimethyl-6-oxaspiro[3.5]nonane-5,9-diones, 11-aryl-12-oxadispiro[3.1.4.3]tridecane-5,13-diones, and 12-aryl-13-oxadispiro[3.1.5.3]tetradecane-5,14-diones.     

Chemistry of oxalyl derivatives of methyl ketones. 40. Reaction of 5-aryl-2,3-dihydro-2,3-furandiones with aryl and aroyl cyanamides

Starting from 5-aryl-2,3-dihydro-2,3-furandiones and benzoyl cyanamide, 2-benzoylamino-6-aryl-1,3-oxazin-4-ones were obtained. It was shown that on reaction of o-chlorophenyl cyanamide with furandiones, 2-imino-3-(o-chlorophenyl)-5-phenacyliden-4-oxazolidones are formed which in acid medium rearrange to 3-(o-chlorophenyl)-5-phenacylideneimidazolidin-2,4-diones and on thermolysis in acid medium they form 2-(o-chloroanilino)-6-aryl-1,3-oxazin-4-ones.For Communication 39, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 166–169, February, 1985.     

Five-membered 2,3-dioxoheterocycles: LXIV. Reactions of 1-methyl-3,4-dihydroisoquinolines with 5-arylfuran-2,3-diones and (Z)-alkyl 4-aryl-2-hydroxy-4-oxobut-2-enoates. Crystal and molecular structure of (2Z,5Z)-3-hydroxy-5-{8,8-dimethyl-2,3,8,9-tetrahydro[1,4]dioxino[2,3-g]isoquinolin-6(7H)-ylidene}-1-phenylpent-2-ene-1,4-dione

5-Arylfuran-2,3-diones and (Z)-alkyl 4-aryl-2-hydroxy-4-oxobut-2-enoates react with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (2Z,5Z)-1-aryl-3-hydroxy-5-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)-ylidene]pent-2-ene-1,4-diones whose structure has been proved by XRD analysis.     

Chemistry of 2-methylene-2,3-dihydrofuran-3-ones. 2. 2-Alkoxycarbonylmethylene-5-aryl-4-halo-2,3-dihydrofuran-3-ones: Synthesis,structure, and properties

Reaction of 5-aryl-4-halo-2,3-dihydrofuran-2,3-diones with alkoxycarbonylmethylenetriphenylphosphoranes has given 2-alkoxycarbonylmethylene-5-aryl-4-halo-2, 3-dihydrofuran-3-ones, which readily add halogens at the 2-exocyclic double bond, and on reaction with arylamines recyclize to give 2-hydroxy-2, 3-dihydropyrrol-3-ones.For Communication 1, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1034–1038, August, 1989.     

Synthesis of 6-aryltetrahydropyran-2,4-diones containing a hexamethylene substituent in positions 3 or 5 of heterocycle

Methyl 3-(1-bromocycloheptyl)-2,2-dimethyl-3-oxopropanoate and methyl 1-(2-bromo-2-methylpropanoyl)cycloheptanecarboxylates react with zinc and arylcarbaldehydes yielding 5-aryl-2,2-dimethyl-4-oxaspiro[5.6]dodecan-1.3-diones and 3-aryl-4,4-dimethyl-2-oxaspiro[5.6]dodecan-1.5-diones respectively.