Cyclic transformations of 5-aryl(or benzyl)-3-(2-bromoethyl- 1,3,4-oxadiazol-2(3H)-ones into 1-aminoimidazolidin-2-one and 5,6-dihydro-4H-1,3,4-oxadiazine derivatives

5-Aryl(or benzyl)-3-(2-bromoethyl)-1,3,4-oxadiazol-2(3H)-ones 3 have been prepared. They were reacted with secondary alkylamines without any change of the heterocycle to give amino derivatives 6 , but with primary alkylamines, cyclic transformation occurred to give 1-acylamino-3-alkylimidazolidin-2-ones 7 . In the presence of sodium alcoholate, bromo compounds 3 were transformed into 2-aryl(or benzyl)-4-alkoxycarbonyl-5,6-dihydro-4H-1,3,4-oxadiazines 9 .     

Synthesis of 3-acylamino-2-oxazolidinone derivatives through cyclic transformations of 5-aryl (or benzyl)-1,3,4-oxadiazol-2(3H)-one derivatives

New 3-acylamino-2-oxazolidinone derivatives 3 were obtained in good yields by reaction of 5-aryl (or benzyl)3-(2-hydroxyethyl)1,3,4-oxadiazol-2(3H)ones 1 with sodium ethylate. Treatment of ethyl 5-aryl-2-oxo-1,3,4-oxadiazole-3(2H)-acetates 7 with aromatic aldehydes in the presence of sodium ethylate or sodium hydride afforded 3-acylamino-5-aryl-4-ethoxycarbonyl-2-oxazolidinone derivatives as two trans- 5 and cis- 6 racemics. Only RS,SR-racemates were obtained with acetophenone under the same conditions.     

Synthesis of 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one. Derivatives and their ring transformation into 5-benzamido-1,2,4-triazolidine-3,5-dione derivatives

Some 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one derivatives 6 and 9 have been synthesized in two ways. The expected thermal ring transformation into 2,5-disubstituted 1,3,4-oxadiazoles did not occur but, by acid hydrolysis of 5-aryl-3-[3-benzylidene-2-methyl(or phenyl)carbazoyl]-1,3,4-oxadiazol-2(3H)-ones 6 , a new ring transformation took place and the corresponding 4-benzamido-1-methyl(or phenyl)-1,2,4-triazolidine-3,5-dione derivatives 11 were formed. The 4-amino-1-phenyl-1,2,4-triazolidine-3,5-dione ( 19 ) has been prepared and its structure was confirmed by some reactions.     

Arbeiten über Phosphorsäure- und Thiophosphorsäure ester mit einem heterocyclischen Substituenten. 2. Mitteilung. Eine verbesserte Methode zur Herstellung von 1, 3, 4-Oxadiazol-2(3H) onen und von Thio- und Dithiophosphorsäure-O,O-dialkyl-S-[(1, 3, 4-oxadiazol-2(3H)-on-3-yl)-methyl]-estern

Some 1,3,4-oxadiazol-2(2H)-ones with aliphatic substituents in 5-position are prepared in good yields and converted via the 3-hydroxymethyl derivatives to the corresponding 3-chloromethyl derivatives which are suitable starting materials for the preparation of insecticidal O,O-dialkyl-S-[(5-subst.-1,3,4-oxidiazol-2(3H)-one-3-yl)-methyl]-thiophosphates and dithiophosphates.     

Synthesis of 8,10-dimethyl-1,10b-dihydro[1,3,5]triazino-[2,1-a]isoindole-2,4,6(3H)-trione by Direct arylation of 1,3,5-triazine-2,4(1H,3H)-dione

Direct arylation of 1,3,5-triazine-2,4(1H,3H)-dione with mesitylene afforded a novel fused heterocyclic system, 8,10-dimethyl-1,10b-dihydro[1,3,5]triazino[2,1-a]isoindole-2,4,6(3H)-trione.     

Synthesis and characterization of 1,3,5-tris((1/2<Emphasis Type="Italic">H</Emphasis>-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione

2,2′,2″-(2,4,6-Trioxo-1,3,5-triazinane-1,3,5-triyl) triacetonitrile (or tris-(cyanomethyl)-isocyanurate) and 1,3,5-tris((1/2H-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione (or tris-(5-tetrazolylmethyl)-isocyanurate) were synthesized with new methods. High yields, simple methodology, and cheapness are advantages of the methods. Furthermore, 1,3,5-tris((1/2H-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione was synthesized in the less hazardous condition. The compounds were characterized by elemental analysis, IR, ¹HNMR, ¹³CNMR and mass spectroscopic analysis. In addition, DSC/TGA measurements were carried out to determine the thermal behavior of the final product.     

Influence of solvents on the molecular and crystal structure of the complex of 1,3-diallyl-5-[3-(diphenylphosphino)propyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione with palladium(II) dichloride

X-ray diffraction study demonstrated that the molecular and crystal structures of the complexes of 1,3-diallyl-5-[3-(diphenylphosphino)propyl]-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (1) with PdCl₂ are determined to a large degree by intra- and intermolecular short contacts between different-polarity groups of the complex molecules. The strength and the existence of the complexes may be affected by the solvents from which the crystals are grown. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1199–1204, July, 2000.     

New synthesis of 4,5-dihydro-1,2,4-triazin-3(2H)-one derivatives through cyclic transformation of 1,3,4-oxadiazol-2(3H)-one derivatives

Some 5-aryl(or benzyl)-2-oxo-1,3,4-oxadiazole-3(2H)-acetones or acetophenones 2 were easily prepared. These compounds reacted with hydrazine derivatives to give 4,5-dihydro-1,2,4-triazin-3(2H)-one derivatives 3 , 4 and 6 in good yields. With phenylhydrazine, the intermediate hydrazones 5 were obtained. Their conversion into triazinones necessitated the presence of sodium ethylate.     

Synthesis,anticancer, and computational studies of 1, 3, 4-oxadiazole-purine derivatives

Theophylline-7-acetic acid (acefylline) ( 3 ) and its derivatives are pharmacologically active compounds and generally recognized as bronchodilators for the treatment of respiratory diseases like acute asthma for over 70 years. In this article, synthesis of 2-((5-((1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-1,3,4-oxadiazol-2-yl)thio)-N-arylacetamides ( 10a-j ) has been reported. All the synthesized derivatives ( 10a-j) were structurally verified by FT-IR, ¹H NMR, ¹³C NMR and evaluated for their anti-cancer (using MTT assay), hemolytic and thrombolytic potential. N-(4-Chlorophenyl)-2-(5-((1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-1,3,4-oxadiazol-2-ylthio)acetamide ( 10g ) was found to be the most active against human liver cancer cell lines (Huh7) having cell viability 53.58 ± 1.28 using 100 μg/mL concentration of compound which was further in-silico modelled to describe the possible mechanistic insights for its anti-proliferative activity. The results of hemolytic and thrombolytic activities indicated that these derivatives were less toxic and hold considerable potential as a drug candidate. 2-(5-((1,3-Dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-1,3,4-oxadiazol-2-ylthio)-N-(2-fluorophenyl)acetamide ( 10c ) of the series was found to be least toxic with 0.1% hemolysis relative to ABTS (95.5%) as positive control. 2-(5-((1,3-Dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-1,3,4-oxadiazol-2-ylthio)-N-(tetrahydro-2H-pyran-4-yl)acetamide ( 10j ) exhibited potent clot lysis activity (90%) as compared to negative control DMSO (0.57%).     

Some 1-aroyl-4,4-dialkylsemicarbazides and their cyclization to afford 5-aryl-1,3,4-oxadiazol-2(3H)-ones

Some 1-aroyl-4,4-dialkylsemicarbazides have been prepared by reacting aroylhydrazides with dimethyl- or diethyl-carbamoyl chloride. In boilingDMF they lose dimethylamine or diethylamine to give 5-aryl-1,3,4-oxadiazol-2(3H)-ones.

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Einige 1-Aroyl-4,4-dialkylsemicarbazide und ihre Cyclisierung zu 5-Aryl-1,3,4-oxadiazol-2(3H)-onen (Kurze Mitteilung)

Zusammenfassung Es wurden mittels Reaktion von Aroyl-hydraziden mit Dimethyl- oder Diethyl-carbamidsäure-chlorid einige 1-Aroyl-4,4-dialkylsemicarbazide dargestellt. Diese verlieren in kochendemDMF Dimethylamin bzw. Diethylamin und geben 5-Aryl-1,3,4-oxadiazol-2(3H)-one.

     

Synthesis of 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones and their conversion into 2-aryl-1,2,4-triazine-3,5-(2H,4H)odiones. A new synthesis of 1-aryl-6-azauracils

Treatment of 6-amino-5-arylazo-1,3-dimethyluracils with urea or N,N′-carbonyldiimidazole gave the respective 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones, which were hydrolyzed with alkali to afford 2-aryl-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carboxylic acids (1-aryl-6-azauracil-5-carboxylic acids). Thermal decomposition of these carboxylic acids gave the corresponding 2-aryl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-6-azauracils). Methylation of the latter with methyl iodide gave the corresponding 2-aryl-4-methyl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-3-methyl-6-azauracils).     

A facile retro-ene reaction of 5-(methoxyamino)-3-aryl-1,3,4-oxadiazol-2(3H)-ones

5-(N-Methoxy-N-methyl)amino-3-aryl-1,3,4-oxadiazol-2(3H)-ones 3 undergo a heteroretro-ene reaction in refluxing methanol in which the leaving enophile is formaldehyde. The resulting 5-(methylimino)-3-aryl-1,3,4-oxadiazolidin-2-one 4 may be viewed as a kinetic product which tautomerizes to the more stable 5-(methylamino)-3-aryl-1,3,4-oxadiazol-2(3H)-one 5 as the thermodynamic product. Comparison of calculated reaction energies reveals that the presence of the heterocyclic ring facilitates the retro-ene reaction, but the expulsion of formaldehyde is predicted to be highly exothermic even in its absence.     

Ring transformations of 1,3,4-oxadiazol-2(3H)-one derivatives into 1-amino and 1,3-diamino-2,4-imidazolidinedione (hydantoin) derivatives

Some ethyl 5-aryl(or benzyl)-2-oxo-1,3,4-oxadiazole-3(2H)-acetates were prepared and treated with ammonia, primary amines or hydrazine to give 1-amino-2,4-imidazolidinedione or 1,3-diamino-2,4-imidazolidinedione derivatives. The 1,3-bis(benzylideneamino)-2,4-imidazolidinedione was obtained by reacting ethyl bromoacetate with the 1,5-dibenzylidenecarbonohydrazide sodium salt.     

Proton-acceptor properties of azahomofullerene and fullerenoaziridine containing a cyanuric acid fragment

¹³C and ¹H NMR and UV spectral studies on 1,3-diallyl-5-[4-(azahomo[60]fullereno)butyl]hexahydro-1,3,5-triazine-2,4,6-trione ([5,6]-open isomer) and 1,3-diallyl-5-[4-(aziridino[60]fullereno)butyl]hexahydro-1,3,5-triazine-2,4,6-trione ([6,6]-closed isomer), as well as quantum-chemical calculations, showed that only the latter possesses weakly basic properties.     

Retro-ene reactions in heterocyclic synthesis. IV. A new synthetic method for 6-hydroxypyrimidin-4(3H)-ones and 1,3,5-triazine-2,4(1H,3H)-diones

N-t-Butylbenzamidines 1 reacted with diphenyl phenylmalonate or diphenyl methylmalonate to give 6-hydroxypyrimidin-4(3H)-ones 4 or 5. Amidines 1 on reaction with diphenyl imidodicarboxylate afforded 1,3,5-triazine-2,4(1H, 3H)-diones 8.     

Dipolare (1:1)-Addukte aus der Reaktion von 3-Amino-2H-azirinen mit 1,3,4-Oxadiazol- und 1,3,4-Thiadiazol-2(3H)-onen

Dipolar 1:1 Adducts from the Reaction of 3-Amino-2H-azirines with 1,3,4-Oxadiazol- and 1,3,4-Thiadiazol-2(3H)-ones 3-Amino-2H-azirines 1 react with 5-(trifluoromethyl)-1,3,4-oxadiazol-2(3H)-one ( 2 ) as well as with different 5-substituted 1,3,4-thiadiazol-2(3H)-ones ( 5a–e ) in 2-propanol at room temperature to give dipolar 1:1 adducts of type 3 and 6 , respectively, in reasonable-to-good yields (Schemes 3 and 6, Tab. 1 and 2). The structure of two of these dipolar adducts, 6a and 6e , which are formally donor-acceptor-stabilized azomethin imines, have been elucidated by X-ray crystallography (Figs. 1-4). In the reaction of 2 and sterically crowded 3-amino-2H-azirines 1c–e with a 2-propyl and 2-propenyl substituent, respectively, at C(2), a 4,5-dihydro-1,2,4-triazin-3(2H)-one of type 4 is formed as minor product (Scheme 3 and Table 1). Independent syntheses of these products proved the structure of 4 . Several reaction mechanisms for the formation of compounds 3 and 4 are discussed, the most likely ones are described in Scheme 4: reaction of 2 as an NH-acidic compound leads, via a bicyclic zwitterion of type A , to 3 as well as to 4 . In the latter reaction, a ring-expanded intermediate B is most probable.     

One-potCuAAC synthesis of (1H-1,2,3-triazol-1-yl)methyl-1,3,4/1,2,4-oxadiazoles starting from available chloromethyl-1,3,4/1,2,4-oxadiazoles

The one-pot CuAAC synthesis of (1H-1,2,3-triazol-1-yl)methyl-1,3,4-oxadiazole and (1H-1,2,3-triazol-1-yl)methyl-1,2,4-oxadiazole derivatives via three-component reaction of consequent nucleophilic substitution of chlorine, with azide, and its further “click” reaction, with alkynes, in the presence of CuI was studied. The utility of newly synthesized 2-(azidomethyl)-1,3,4/1,2,4-oxadiazoles and chloromethyl-1,3,4/1,2,4-oxadiazole derivatives was explored, and their limitations were determined. Novel 5-([4-aryl-1H-1,2,3-triazol-1-yl]methyl)-3-(aryl)-1,2,4-oxadiazoles, 2-([4-aryl-1H-1,2,3-triazol-1-yl]methyl)-5-(aryl)-1,3,4-oxadiazoles were obtained in good yields.     

1,2,4-Triazines, 9. The synthesis of novel 4-amino-1,6-dihydro-1,2,4-triazinones

3-Alkylthio-4-amino-1,6-dihydro-1,2,4-triazin-5(4H)-ones were synthesized by the reduction of 3-thio-4-amino-1,2,4-triazine-3,5(2.H,4H)-diones and successive S-alkylation. The regiospecific alkylation on the N-1 position or the exo amino group leads to a variety of 1,6-dihydro-1,2,4-triazin-5(4H)-one derivatives. An alternative synthesis of 3-thio-4-amino-1,6-dihydro-1,2,4-triazine-3,5(2H,4H)-diones was accomplished through the cyclization of 1-thiocarbohydrazidoacetamide derivatives.     

Propylene oxide assisted one-pot,tandem synthesis of substituted-1,3,4-oxadiazole-2(3H)-ones in water

It has been developed for the synthesis of substituted-1,3,4-oxadiazole-2(3H)-one derivatives via a novel one-pot, tandem procedure assisted by propylene oxide. The 5-substitued-1,3,4-oxadiazole-2(3H)-ones and 3,5-disubstitued-1,3,4-oxadiazole-2(3H)-ones were, respectively, obtained from three-component reaction of acylhydrazines, carbon disulfide, and propylene oxide, and four-component reaction of acylhydarazines, carbon disulfide, propylene oxide, and organic halides. The reactions were carried out using water as solvent in the presence of potassium phosphate to afford the expected products in good to excellent yields.     

A new simple synthesis of 3,5-disubstituted 1-amino-1,3,5-triazine-2,4,6-triones from ethoxycarbonylhydrazones and isocyanates

The 3,5-disubstituted 1-amino-1,3,5-triazine-2,4,6-triones were synthesized in good yields from aromatic aldehyde or ketone ethoxycarbonylhydrazones by treatment with aryl or methyl isocyanates in boiling triethylamine followed by hydrolysis with hydrochloric acid solution.