Antioxidant properties of some 5-ethoxycarbonyl-substituted 3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones (-thiones) and their derivatives

Inhibiting properties of some synthesized 5-ethoxycarbonyl-substituted 3,4-dihydropyrimidin-2(1H)-ones (-thiones) and their derivatives in model reactions were studied.     

Synthesis of substituted 3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones and pyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones by the Biginelli reaction with 3,5-Di-<Emphasis Type="Italic">tert</Emphasis>-butyl-4-hydroxybenzaldehyde

Three-component acid-catalyzed cyclocondensation of 3,5-di-tret-butyl-4-hydroxybenzaldehyde with urea and ethyl acetoacetate or α-nitroacetophenone (Biginelli reaction) under homogeneous conditions gave the corresponding 5-substituted 3,4-dihydropyrimidin-2(1H)-ones having in position 4 of the heteroring an aryl substituent with sterically shielded hydroxy group. The condensation catalyzed by inorganic salts (Fe³⁺, Co²⁺, Zn²⁺, Li⁺) was successful only with ethyl acetoacetate as initial methylene-active component. Under analogous conditions, acetophenone and 4-fluoroacetophenone gave rise to 4,6-diarylpyrimidin-2(1H)-ones which are capable of undergoing phenol-quinonemethide tautomerism.     

1,3-Dibromo-5,5-dimethylhydantoin as a useful reagent for efficient synthesis of 3,4-dihydropyrimidin-2-(1<Emphasis Type="Italic">H</Emphasis>)-ones under solvent-free conditions

Efficient syntheses of 3,4-dihydropyrimidin-2-(1H)-ones and the corresponding thioxo derivatives using 1,3-dibromo-5,5-dimethylhydantoin (DBH) catalysis of a one-pot three-component Biginelli reaction of aldehydes, ethyl acetoacetate, and urea or thiourea under microwave irradiation are described. The advantages of this method are its short reaction times, high yields of the products, inexpensive and commercially available catalyst, and solvent-free conditions. Typical isolated yields exceed 70 % for arylaldehydes (9 examples) and aliphatic aldehydes (2 examples).     

Sulfonic acid-functionalized titanomagnetite nanoparticles as recyclable heterogeneous acid catalyst for one-pot solvent-free synthesis of 3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones/thiones

Sulfonic acid-functionalized titanomagnetite (Fe_3?x Ti _x O₄@SO₃H) nanoparticles were prepared by grafting sulfonic acid groups on Fe_3?x Ti _x O₄ nanoparticles. This new heterogeneous acid nanocatalyst demonstrated an efficient catalytic performance in the one-pot synthesis of dihydropyrimidin-2(1H)-one/thione derivatives under solvent-free conditions with high yields. The nanocatalyst could easily be separated from the reaction mixture simply by using an external magnet, recycled and reused for several times with no significant loss of catalytic activity. These nanoparticles were characterized by different physicochemical techniques, such as Fourier transform infrared, scanning electron microscopy, energy-dispersive X-ray analysis, thermogravimetric and vibrating sample magnetometer (VSM) analyses.     

Regioselective synthesis of polyfluoroalkyl-substituted 7-(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-1-yl)-6,7-dihydro-1<Emphasis Type="Italic">H</Emphasis>-indazol-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

3-Polyfluoroalkyl-6,6-dimethyl-7-(1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-indazol-4(5H)-ones were synthesized with high regioselectivity by 1,3-dipolar cycloaddition of terminal alkynes (phenylacetylene, hex- 1-yne, hept-1-yne, and but-3-yn-1-ol) to 7-azido-6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol-4(5H)-ones which were prepared by bromination of 6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol- 4(5H)-ones with N-bromosuccinimide in anhydrous carbon tetrachloride, followed by treatment of the corresponding 7-bromo derivatives with sodium azide.     

An efficient synthesis of 3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-one and 5,6-diphenylpyrimidine derivatives under solvent-free and base conditions

An efficient and convenient Biginelli-like reaction one-pot synthesis of a series of 4-aryl-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one and 4-aryl-5,6-diphenylpyrimidine derivatives under solvent-free conditions from the reaction of aromatic aldehydes, 1,2-diphenylethanone, urea, guanidine carbonate or acetamidine hydrochloride has been reported. This methodology has the advantages of short reaction time, mild reaction conditions, easy work-up and environmental friendliness. Moreover, 4-aryl-5,6-diphenylpyrimidine derivatives were first reported in this process. The structures of the title compounds were further determined by X-ray diffraction. More importantly, different from general Biginelli reaction, this reported method was carried out under base conditions.     

Selective acylation of 5-nitro- and 5-ethoxycarbonyl-4,6-diaryl-3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

The acetylation and chloroacetylation of 5-nitro- and 5-ethoxycarbonyl-substituted 4,6-diaryl-3,4-dihydropyrimidin-2(1H)-ones proceeds regioselectively at the N³ atom of the heterocycle whereas the acetylation of the 5-aryloxy-substituted analog results in a mixture of N¹- and N³-acetylated regioisomers.     

Synthesis and calming activity of helicid derivatives containing the 3,4-dihydropyrimidin-2(<Emphasis Type="Italic">H</Emphasis>)-one and 3,4-dihydropyrimidine-2(<Emphasis Type="Italic">H</Emphasis>)-thione moiety

A series of novel helicid derivatives containing 3,4-dihydropyrimidin-2(1H)-one and 3,4-dihydropyrimidine2(1H)-thione moiety (3a–3f and 4a–4f) were synthesized starting from helicid. The structure of the new compounds were characterized by ¹H NMR, IR and HR-MS spectra. The sedative-hypnotic activities of the target compounds were evaluated using the test of spontaneous locomotor activity in mice. All of the derivatives produced moderate to high activities; in particular, compound 4a presented the most potent sedative-hypnotic effect in comparison to the other derivatives, and derivatives 3a, 3c, 3d, 3e and 3f also showed potent activities.     

Carboxamides of Dihydropyridin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

Summary. 3-Carboxamides and 3-carboxanilides of 6-alkyl and 6-aryldihydropyridin-2(1H)-ones have been prepared via different reaction pathways. All synthesized amides show hydrogen bonds in their NMR spectra. The 4-hydroxy compounds were obtained as a mixture of tautomers. Their configurations were elucidated by NMR experiments.Received December 16, 2002; accepted December 20, 2002 Published online June 2, 2003     

Reaction of methyl 1-bromocyclopentane- and 1-bromocyclohexanecarboxylates with zinc and 2-arylmethylidene-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-inden-1-ones or 2-arylmethylidene-3,4-dihydronaphthalen-1(2<Emphasis Type="Italic">H</Emphasis>)-ones

Methyl 1-bromocyclopentanecarboxylate and methyl 1-bromocyclohexanecarboxylate reacted with zinc and 2-arylmethylidene-2,3-dihydro-1H-inden-1-ones or 2-arylmethylidene-3,4-dihydronaphthalen-1(2H)-ones to give 4′-aryl-4′,5′-dihydro-2′H-spiro[cyclopentane(cyclohexane)-1,3′-indeno[1,2-b]pyran]-2′-ones or 4-aryl-5,6-dihydrospiro[benzo[h]chromene-3,1′-cyclopentane(cyclohexane)]-2(4H)-ones, respectively.     

Synthesis and transformations of 3-acetylpyridine-2(1<Emphasis Type="Italic">H</Emphasis>)-thiones

Reactions of substituted 3-cyanopyridine-2(1H)-thiones with methyllithium gave 3-acetylpyridine-2(1H)-thiones. The best results were achieved by adding a solid-state thione to a solution of methyllithium in ether (thione: MeLi = 1: 3). The compounds obtained and their 3-pentanoyl analogs were used to synthesize a number of fused heterocyclic systems. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1504–1507, July, 2008.     

Synthesis of (<Emphasis Type="Italic">S</Emphasis>)-(-)-1,4-diaryl-6-methyl-4-trifluoromethyl-3,4-dihydropyrimidine-2(1<Emphasis Type="Italic">H</Emphasis>)-thiones

(S)-(+)-4-Amino-4-aryl-5,5,5-trifluoropentan-2-one reacted with aryl isothiocyanates containing electron-withdrawing substituents to give (S)-(−)-1,4-diaryl-6-methyl-4-trifluoromethyl-3,4-dihydropyrimidine-2(1H)-thiones.     

Cyclizations of monocyclic 5-nitropyridin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

Reactions of 5-nitropyridin-2(1H)-one and its N-methyl derivative with hydrazine hydrate led to the formation of (1H-pyrazol-3-yl) acetohydrazide. Under analogous conditions, 1,3-dimethyl-5-nitropyridin2(1H)-one gave rise to 2-(1H-pyrazol-3-yl)propionohydrazide, while 6-methyl-5-nitropyridin-2(1H)-one was converted into (5-methyl-1H-pyrazol-3-yl)acetohydrazide. Hydrazinolysis of 4-methyl-5-nitropyridin-2(1H)-one resulted in the formation of 3-methyl-4-nitro-1H-pyrazole. The mechanism of recyclization of nitropyridine derivatives by the action of hydrazine hydrate was studied using 5-nitropyridin-2(1H)-one and 1-methyl-5-nitropyridin-2(1H)-one as examples.     

5,7-Dihydropyrrolo[3,4-<Emphasis Type="Italic">d</Emphasis>][1,2]diazepin-1(2<Emphasis Type="Italic">H</Emphasis>)-ones. Synthesis and transformations

A preparative procedure has been developed for the synthesis of substituted 5,7-dihydropyrrolo-[3,4-d][1,2]diazepines by recyclization of 6-phenylpyrano[3,4-c]pyrrol-4(2H)-one with hydrazine hydrate. The stability of the seven-membered ring in the products under acidic conditions, alkylation, and heteroring fusion to the diazepine ring have been studied.     

Reaction 5-(Arylmethylidene)pyrimidine-2,4,6(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>,5<Emphasis Type="Italic">H</Emphasis>)-triones with L-Proline and Aldehydes

Boiling in toluene of 5-(arylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-triones with L-proline and aldehyde led to the formation of previously unknown substituted 1′-arylhexahydro-1H-spiro[pyrimidine-5,2′-pyrrolysine]-2,4,6(1H,3Н,5Н)-triones.     

Tautomerism of azacycles: III. Molecular and crystal structures of 3<Emphasis Type="Italic">H</Emphasis>-and 2-phenyl-1<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>-4,5-dihydro-1,2,4-triazole-5-thiones

Compounds capable of tautomerism: sulfanyl-1,2,4-triazole, its C-phenyl derivative, and the crystal hydrate of the latter, were studied by single crystal X-ray diffraction. In the crystals they exist in the form of 3-R-1(H),4(H)-4,5-dihydro-1,2,4-triazole-5-thione with a considerable contribution of the bipolar structure. Published data on the tautomerism of sulfanyl-1,2,4-triazoles and their N-substituted analogs and on the correlation between the spectral characteristics and structures of sulfanyl-1,2,4-triazoles capable of tautomerism are discussed.     

New Strategy of the Synthesis of 3,4-Dihydropyrimido[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazol-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

A new procedure has been developed for preparative synthesis of 3,4-dihydropyrimido[1,2-a]-benzimidazol-2(1H)-ones by thermal intramolecular heterocyclization of 3-[2-(propylsulfanyl)- and 2-(benzylsulfanyl)-1H-benzimidazol-1-yl]propanehydrazides and 3-[2-(benzylsulfanyl)-1H-benzimidazol-1-yl]-propanamide.     

Efficient synthesis of bis-indolyloxindoles from (phenylimino)indolin-2-ones and 1<Emphasis Type="Italic">H</Emphasis>-indole catalyzed by <Emphasis Type="Italic">p</Emphasis>-toluenesulfonic acid

p-Toluenesulfonic acid (p-TSA) efficiently catalyzed the reaction of (phenylimino)indolin-2-ones with 1H-indole in dichloromethane at room temperature to afford 3,3-di(indolyl)indolin-2-ones in 2-3 min with high yields.