Synthesis and biotests of 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4<Emphasis Type="Italic">H</Emphasis>)-ones and <Emphasis Type="Italic">N</Emphasis>-methyl-3,5-dihydro-4<Emphasis Type="Italic">H</Emphasis>-imidazol-4-ones as combretastatin A-4 analogs

A series of 2-aryl-5-arylmethylidene-1,3-oxazol-5(4H)-ones and 2-aryl-5-arylmethylidene-N-methyl-3,5-dihydro-4H-imidazol-4-ones was synthesized as structural analogs of combret- astatin A-4 (a compound possessing antitumor activity). (5Z)-5-[(4-Methoxyphenyl)methyl-idene]-3-methyl-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one was found to exhibit the highest cytotoxicity against cells of human A549 lung carcinoma line (EC₅₀ = 6±0.8 μmol L^?1).     

Reaction of 5-arylfuran-2(3<Emphasis Type="Italic">H</Emphasis>)-ones with amines

5-(4-Chlorophenyl)- and 5-phenylfuran-2(3H)-ones reacted with guanidine carbonate at the methylene group in the unsaturated lactone molecule, leading to the formation of 4-(2-aryl-5-oxo-2,5-dihydrofuran-2-yl)-5-aryltetrahydrofuran-2-ones, while 5-(4-methylphenyl)furan-2(3H)-one under analogous conditions gave rise to N,N′-bis[4-(4-methylphenyl)-4-oxobutanoyl]guanidine. The reactions of 5-arylfuran-2(3H)- ones with thioacetamide afforded 4-aryl-N-{1-[5-aryl-2-oxo-2,3-dihydrofuran-3-ylidene]ethyl}-4-oxobutanamides. The corresponding N-(4-aryl-4-oxobutanoyl)thioureas were obtained by heating 5-arylfuran-2(3H)-ones with thiourea.     

Synthesis of 2-Aryl-4-(R-sulfanylmethyl)-3-methyl-6,7-dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyridazin-7-ones

Bromination of ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates gave ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazol-3-carboxylates which were used to alkylate benzenethiol and heterocyclic thiones at the sulfur atom. Reactions of the resulting S-alkylation products with hydrazine or methylhydrazine involved closure of pyridazine ring to afford 2-aryl-3-methyl-4-[phenyl(or hetaryl)sulfanylmethyl]-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-7-ones.     

Reaction of 1-aryl-2,2-dibromoalkan-1-ones with zinc and 4-aroyl-<Emphasis Type="Italic">1H</Emphasis>-benzo[<Emphasis Type="Italic">c</Emphasis>]oxepin-3-ones

Zinc enolates formed from the substituted 1-aryl-2,2-dibromoalkan-1-ones and zinc react with 4-aroyl-1H-benzo[c]oxepin-3-ones to form 1-alkyl-1-aroyl-1a -aroyl-1,1a,4,8b-tetrahydro-3-oxabenzo[a]cyclopropa c]cyclohepten-2-ones.     

Reaction of acetylenedicarboxylic acids esters with 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-1-carbothioamides and 3,4,5,6-tetrahydro-2<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazepine-3-thiones

The reactions of dimethyl acetylenecarboxylate with 3,4,5,6-tetrahydro-2H-1,2,4-triazepine-3-thiones and 4,5-dihydro-1H-pyrazole-1-carbothioamides are convenient methods for the synthesis of 7,8-dihydrothiazolo[3,2-b][1,2,4]triazepin-3-ones derivatives and methyl esters of (2Z)-[2-(4,5-dihydro-1H-pyrazol-1-yl)-4-oxo-1,3-thiazol-5(4H)-ylidene]acetic acids, respectively. The reaction of methyl propynoates with 4,5-dihydro-1H-pyrazole-1-carbothioamides or with 5,5,7-trimethyl-2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thione gives 2-(4,5-dihydro-1H-pyrazol-1-yl)-4H-1,3-thiazin-4-ones.     

Azacycloalkanes: XXXIX. New Syntheses of 1<Emphasis Type="Italic">H</Emphasis>-Pyrrole-1-carboxylic acid and 1,2-dihydropyrrolo-[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrazin-3(4<Emphasis Type="Italic">H</Emphasis>)-one derivatives

New procedures have been developed for the synthesis of α-(2-formyl-1H-pyrrol-1-yl)-substituted carboxylic acids, α-(2-R-aminomethyl-1H-pyrrol-1-yl)-substituted carboxylic acids, and 1,2-dihydropyrrolo-[1,2-a]pyrazin-3(4H)-ones on the basis of furfurol and α-amino acids.     

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.     

Recyclization of 1,3-dialkyl-6-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,5(3<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>)-diones into imidazole derivatives

Treatment of 5-amino-1,3-dialkyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones with sodium nitrite in aqueous HCl gave 1,3-dialkyl-1H-imidazo[4,5-b]pyridine-2,5(3H,4H)-diones which were nitrated with potassium nitrate in sulfuric acid to 6-nitro derivatives, and the latter underwent recyclization into 4-amino-1,3-dialkyl-5-(1H-pyrazol-5-yl)-2,3-dihydro-1H-imidazol-2-ones by the action of hydrazine hydrate.     

Reactions of 1,3-Dialkyl-5-amino-1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-ones with acetylacetone and ethyl acetoacetate

1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones reacted with acetylacetone to give the corresponding 4-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)pent-3-en-2-ones which underwent intramolecular cyclization to 1,3-dialkyl-5,7-dimethyl-1,3-dihydro-2H-imidazo[4,5-b]-[1,8]naphthyridin-2-ones on heating in polyphosphoric acid or diphenyl ether. Analogous reaction of 1,3-dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones with ethyl acetoacetate led to the formation of ethyl 3-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)but-2-enoates whose cyclization afforded 1,3-dialkyl-8-hydroxy-7-methyl-1,3-dihydro-2H-imidazo[5,4-b][1,8]naphthyridin-2-ones.     

Synthesis of (<Emphasis Type="Italic">S</Emphasis>)-(+)-6-aryl-3-acetyl-6-trifluoromethyl-5,6-dihydropyridin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

(S)-(+)-4-Amino-4-aryl-5,5,5-trifluoropentan-2-ones reacted with ethyl acetoacetate and ethyl trifluoroacetoacetate to give (S)-(+)-6-aryl-3-acetyl(or trifluoroacetyl)-6-trifluoromethyl-5,6-dihydropyridin-2(1H)-ones.     

Synthesis of methyl 7-aryl-6-(2-thenoyl)-4,7-dihydro-tetrazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-5-carboxylates and their reaction with hydrazine hydrate

Fusion of methyl 4-(2-thienyl)-2,4-dioxobutanoate with 1H-tetrazol-5-amine monohydrate and aromatic aldehyde gave methyl 7-aryl-6-(2-thenoyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-5-carboxylates which reacted with an equimolar amount of hydrazine hydrate at 180–190°C under solvent-free conditions to produce 9-aryl-8-(2-thienyl)-4,9-dihydrotetrazolo[1′,5′: 1,2]pyrimido[4,5-d]pyridazin-5(6H)-ones.     

Microwave-assisted synthesis and antifungal activity of some new 1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazole derivatives

A number of 3-aryl-4-arylmethylideneamino-4,5-dihydro-1H-1,2,4-triazol-5-ones were synthesized by reaction of the corresponding aromatic aldehydes with 4-amino-3-aryl-1H-1,2,4-triazol-5-ones in anhydrous ethanol under microwave irradiation. The newly synthesized 1H-1,2,4-triazole derivatives were tested for antimicrobial activity. They showed no antibacterial activity but slight mycostatic activity against some Candida species. Published in Russian in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 12, pp. 1843–1847. The text was submitted by the authors in English.     

Synthesis and structures of benzo[<Emphasis Type="Italic">cd</Emphasis>]furo[2,3-<Emphasis Type="Italic">f</Emphasis>]indol-4(5<Emphasis Type="Italic">H</Emphasis>)-one derivatives

A procedure was developed for the synthesis of derivatives of the new heterocyclic system, benzo[cd]furo[2,3-f]indole, based on the cyclodehydration of 6-acylmethyloxy-1-alkyl-benzo[cd]indol-2(1H)-ones. Either 7- or 8-aryl derivatives of benzo[cd]furo[2,3-f]indol-4(5H)-ones can be prepared depending on the reaction conditions. The molecular and crystal structures of 7- and 8-phenylbenzo[cd]furo[2,3-f]indol-4(5H)-ones were established by X-ray diffraction.     

Synthesis of 4-trifluoromethyl-3,4-dihydro-1,3,5-triazino[2,1-<Emphasis Type="Italic">a</Emphasis>]isoindol-2-ones by cyclocondensation of 1-aryl-1-chloro-2,2,2-trifluoroethyl isocyanates with 3-amino-1-arylimino-1<Emphasis Type="Italic">H</Emphasis>-isoindoles

4-Trifluoromethyl-3,4-dihydro-1,3,5-triazino[2,1-a]isoindol-2-ones were prepared by reaction of 1-aryl-1-chloro-2,2,2-trifluoroethyl isocyanates with 3-amino-1-arylimino-1H-isoindoles in the presence of triethylamine. In some events alongside the main product isomeric 2-trifluoromethyl-2,3-dihydro-1,3,5-triazino[2,1-a]isoindol-4-ones were obtained. The regioselectivity of the reaction is affected by sterical and electronic characteristics of substituents and by temperature.     

Halocyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">de</Emphasis>]isoquinoline-1,3(2<Emphasis Type="Italic">H</Emphasis>)-dione

Cyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione by the action of iodine, bromine, or sulfuryl chloride gave 2-(2-{4-[4,5-dihydro-5-(halomethyl)-thiazol-2-yl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione hydrohalides which were converted into 2-{2-[4-(5-methylthiazol-2-yl)piperazin-1-yl]ethyl}-1H-benzo[de]isoquinoline-1,3(2H)-dione.     

Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.     

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.     

Chemistry of 2-ylidenefuran-3(2<Emphasis Type="Italic">H</Emphasis>)-ones: XIX. Reaction of 5-aryl-2(oxoylidene)furan-3(2<Emphasis Type="Italic">H</Emphasis>)-ones with carboxylic acid hydrazides

2-[2-(4-Chlorophenyl)-2-oxoethylidene]-5-phenylfuran-3(2H)-one and methyl (5-aryl-3-oxo-2,3-dihydrofuran-2-ylidene)acetates react with carboxylic acid hydrazides to give the corresponding 3-substituted 2-acyl-6-aryl-3-hydroxy-2,3-dihydropyridazin-4(1H)-ones. Specificities of the product structure are discussed.     

Cyclofunctionalization of 6-alkenylsulfanylpyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]-pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones with arenesulfenyl chlorides

Reactions of 6-allylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one with arenesulfenyl chlorides in chloroform gave products of addition of the latter at the exocyclic double bond, while analogous reactions in acetic acid in the presence of LiClO₄ were accompanied by intramolecular electrophilic cyclization involving the N⁷ atom. 6-Cinnamylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one reacted with arenesulfenyl chlorides in acetic acid in the absence of electrolyte to produce fused pyrazolo[4′,3′: 5,6]pyrimido[2,1-b][1,3]thiazine derivatives. Introduction of a bulky phenyl group into position 1 of the pyrazolo[3,4-d]pyrimidine system reduces the yield of the corresponding intramolecular cyclization product at N⁷ as a result of concurrent formation of acyclic addition product. DOI     

2-Spiroanellated 1,3-Benzodioxoles from the Reaction of 2,3-Dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrol-3-ones with Tetrachloro-1,2-benzoquinone

Summary. Novel spiro[1,3-benzodioxole-2,2-(2,3-dihydro-1H-pyrrol-3-ones)] were obtained from 2-aminomethylene-2,3-dihydropyrrol-3(1H)-ones and tetrachloro-1,2-benzoquinone in ethanol at room temperature. However, in addition, 3,4-dichloro-7-methoxy-5-(4-methoxyphenyl)-5,10-dihydrophenazine-1,2-dione was formed in the reaction of 1-(4-methoxyphenyl)-2-(4-methoxyphenylaminomethylene)-4,5-diphenyl-1,2-dihydropyrrol-3-one with tetrachloro-1,2-benzoquinone.