Synthesis of 1,2,4- and 1,3,4-oxadiazoles from 1-aryl-5-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-4-carbonyl chlorides

5-Substituted 2-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazoles were synthesized by reaction of 1-aryl-5-methyl-1H-1,2,3-triazole-4-carbonyl chlorides with the corresponding 5-substituted 1H-tetrazoles. 5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl chloride reacted with N′-hydroxybenzimidamides to give 3-aryl-5-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazoles. Reactions of 4-(5-methyl-1H-1,2,3-triazol-1-yl)benzoic acid with N′-hydroxybenzimidamides resulted in the formation of 3-aryl-5-[4-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl]-1,2,4-oxadiazoles.     

Synthesis of N-aryl- and <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diethyl-9-methyl-11-sulfanylidene-8-oxa-10,12-diazatricyclo[7.3.1.0<Superscript>2,7</Superscript>]trideca-2,4,6-triene-13-carboxamides

Three-component condensation of N-aryl- and N,N-diethyl-3-oxobutanamides with salicylaldehyde and thiourea in ethanol in the presence of sodium hydrogen sulfate afforded N-aryl- and N,N-diethyl-9-methyl-11-sulfanylidene-8-oxa-10,12-diazatricyclo[7.3.1.0^2,7]trideca-2,4,6-triene-13-carboxamides. Reaction of the same compounds in the absence of a catalyst under solvent-free conditions gave N-aryl-6-(2-hydroxyphenyl)-4-methyl-2-sulfanylidene-1,2,3,6-tetrahydropyrimidine-5-carboxamides.     

Electrophilic intramolecular cyclization of functional derivatives of unsaturated compounds: VIII. Cyclization of 4-aryl-<Emphasis Type="Italic">N</Emphasis>-(thiophen-3-yl)but-3-enamides by the action of polyphosphoric acid and chlorosulfanylarenes

Intramolecular cyclization of 4-aryl-N-(thiophen-3-yl)but-3-enamides on heating in polyphosphoric acid afforded 8-aryl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones and 5-aryl-1-(thiophen-3-yl)pyrrolidin-2-ones. Cyclofunctionalization of the title compounds with (chlorosulfanyl)benzene and 4-(chlorosulfanyl)-toluene led to the formation of 8-aryl-7-arylsulfanyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones or their mixtures with 5-aryl-4-arylsulfanyltetrahydrofuran-2-ones. 1-(Chlorosulfanyl)-4-nitrobenzene reacted with 4-(4-methylphenyl)-N-(thiophen-3-yl)but-3-enamide and 4-(4-fluorophenyl)-N-(thiophen-3-yl)but-3-enamide to give 5-(4-methylphenyl)-4-(4-nitrophenylsulfanyl)-1-(thiophen-3-yl)pyrrolidin-2-one and 5-(4-fluorophenyl)-4-(4-nitrophenylsulfanyl)tetrahydrofuran-2-one, respectively.     

Polyfunctional imidazoles: XIV. 4-sulfonyl-5-formyl-1<Emphasis Type="Italic">H</Emphasis>-imidazoles

Oxidative chlorination of 1-aryl-4-benzylsulfanyl-1H-imidazole-5-carbaldehydes gave 1-aryl-5-formyl-1H-imidazole-4-sulfonyl chlorides which reacted with secondary amines and phenols to produce the corresponding N,N-disubstituted 5-formylimidazole-4-sulfonamides and aryl sulfonates. The reaction of 1-aryl-5-formyl-1H-imidazole-4-sulfonyl chlorides with sodium azide, followed by reduction of the resulting sulfonyl azides, led to the formation of N-unsubstituted 5-formylimidazole-4-sulfonamides, and the reaction with alcohols, to 5-formylimidazole-4-sulfonic acids.     

Five-membered 2,3-dioxo heterocycles: LII. Reactions of 5-aryl-4-(quinoxalin-2-yl)-2,3-dihydrofuran-2,3-diones with Schiff bases and dicyclohexylcarbodiimide. Crystalline and molecular structure of substituted 2-(4-oxo-3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>1,3-oxazin-5-yl)quinoxalines

Aroyl(quinoxalinyl)ketenes generated by thermolysis of 5-aryl-4-(quinoxalin-2-yl)-2,3-dihydrofuran-2,3-diones react with N-benzylideneanilines and N,N’-dicyclohexylcarbodiimide according to the [4+2]-cycloaddition pattern where the aroylketene acts as diene, and C=N component, as dienophile, to give 3-aryl-2-(2,3,6-triaryl- and 6-aryl-3-cyclohexyl-2-cyclohexylimino-4-oxo-3,4-dihydro-2H-1,3-oxazin-5-yl)quinoxalines. The structure of two cycloaddition products was proved by X-ray analysis.     

4-aryl-2-hydroxy-4-oxobut-2-enoic acids <Emphasis Type="Italic">N</Emphasis>-(2-pyridyl)amides in reactions with diazo compounds

Reactions of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids N-(2-pyridyl)amides with diazomethane, diazoethane, diaryldiazomethanes, and diazofluorene lead to the formation of 2-alkoxy-4-aryl-4-oxobut-2-enoic acids N-(2-pyridyl)amides, 3-aroyl-5-methylpyrazole-4-carboxylic acids N-(2-pyridyl)amides, and 3-alkoxy-3-(2-aryl-2-oxoethyl)-2,3-dihydro-2-oxoimidazo[1,2-a]pyridines. The composition and structure of compounds obtained depend on the nucleophilic nature of the diazo compound and on the character of substituents in the aryl and pyridine parts of the substrate.     

Chemistry of Iminofurans: XV. Decyclization of Ethyl 2-[5-Aryl-2-oxofuran-3(2<Emphasis Type="Italic">H</Emphasis>)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylates by the Action of Secondary Amines

Ethyl 2-[5-aryl-2-oxofuran-3(2H)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylates reacted with secondary amines to give 4-aryl-2-(thiophen-2-yl)-4-oxobutanamides, whereas their reaction with piperazine afforded N,N′-disubstituted piperazine derivatives regardless of the reactant ratio.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with bis(guanidinium) carbonate

Reactions of N-aryl-3-oxobutanethioamides with bis(guanidinium) carbonate lead to the formation of N-aryl-3-guanidinobut-2-enethioamides, 4-arylamino-6-methylpyrimidin-2-amines, guanidinium acetate, and arylamines, depending on the temperature conditions.     

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).     

Transformations of <Emphasis Type="Italic">N</Emphasis>-(2-acylaryl)benzamides and their analogs under the Camps cyclization conditions

N-(2-Acylaryl)benzamides and analogous N-substituted furan-2-, thiophene-2-, and cyclopropane-carboxamides in the systems EtONa–EtOH, EtONa–THF, and t-BuOK–t-BuOH undergo Camps cyclization to 2-aryl-, 2-hetaryl-, and 2-cyclopropylquinolin-4(1H)-ones with high yields. The same substrates in the system t-BuOK (5 equiv)–THF are converted mainly to the corresponding N-(2-hydroxyaryl) amides as a result of oxidative transformation of the acyl fragment into hydroxy group.     

Chemistry of iminofurans: XII.<Superscript>1</Superscript> Synthesis of 2-(arylimino)furan-3(2<Emphasis Type="Italic">H</Emphasis>)-ones and their reaction with amines

2-(Arylimino)-5-(het)arylfuran-3(2H)-ones were synthesized by reaction of 5-(het)arylfuran-2,3-diones with N-(triphenyl-λ⁵-phosphanylidene)anilines, and their aminolysis afforded N-aryl-4-amino-4-(het)aryl-2-oxobut-3-enamides.     

Hetero-diels–alder reaction of 5-ylidene-4-sulfanylidene-1,3-thiazolidin-2-ones with <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>′-bis(methoxycarbonyl)-1,4-benzoquinone diimine

Hetero-Diels–Alder reaction of 5-(propan-2-ylidene)-4-sulfanylidene-1,3-thiazolidin-2-one with N,N′-bis(methoxycarbonyl)-1,4-benzoquinone diimine in boiling toluene afforded 87% of dimethyl 9,9-dimethyl-2-oxo-8a,9-dihydro-2H-thiochromeno[2,3-d][1,3]thiazole-5,8(3H,4aH)-diylidenedicarbamate. Analogous reactions of 5-benzylidene-, 5-{[4-(dimethylamino)phenyl]methylidene}-, and 5-[(2-hydroxyphenyl)-methylidene]-4-sulfanylidene-1,3-thiazolidin-2-ones led to the formation of the corresponding dimethyl 9-aryl-2-oxo-3,9-dihydro-2H-thiochromeno[2,3-d][1,3]thiazole-5,8-diyldicarbamates in 64–82% yield.     

Reaction of Zinc Enolates Formed from 1-Aryl-2,2-dibromoalkanones and Zinc,with Substituted 2-Oxochromene-3-carbohydrazides

Zinc enolates formed from 1-aryl-2,2-dibromoalkanones and zinc react with N′-methyl-N′-phenyl- and N′-benzylidene-N-phenylhydrazides of 2-oxochromene-3-carboxylic acid to form the corresponding hydrazides of 1-alkyl-1-aroyl-2-oxo-1a,7b-dihydrocyclopropa[c]chromene-1a-carboxylic acid as a single geometric isomer.     

Azolyl-substituted 1,2,3-triazoles

Huisgen reaction of (E)-1,5-diarylpent-2-en-4-yn-1-ones and (E)-1,5-diarylpent-1-en-4-yn-3-ones afforded 1-aryl-3-(5-aryl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones and 3-aryl-1-(5-aryl-1H-1,2,3-triazol-4-yl)-prop-2-en-1-ones, respectively. (E)-1-Aryl-3-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones reacted with hydrazine hydrate and phenylhydrazine to give 72–93% of 4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles which underwent dehydrogenation on heating in boiling acetic acid with formation of the corresponding pyrazole derivatives. The molecular structures of (E)-3-phenyl-1-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-one and 4-[3-(4-methylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-yl]-5-phenyl-1H-1,2,3-triazole were studied by X-ray analysis. 4-(3-Aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles showed toxicity against Daphnia magna.     

Cyclocondensation of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 2-aminoimidazole and 2-aminobenzimidazole

Cyclization of N-aryl-3-oxobutanethioamides with 2-aminoimidazole and 2-aminobenzimidazole gave 7-methyl-5,8-dihydroimidazo[1,2-a]pyrimidine-5-thione or 2-methylpyrimido[1,2-a]benzimidazole-4(1H)-thione and 4-(arylamino)-2-methylpyrimido[1,2-a]benzimidazoles whose ratio depends on the nature of aryl substituents in the initial butanethioamides and on the presence of a protic solvent.     

Synthesis of methyl 4-aryl-2-{[4-(carbamimidoylsulfamoyl)- phenyl]amino}-4-oxobut-2-enoates

Methyl aroylpyruvates reacted with 4-amino-N-carbamimidoylbenzene-1-sulfonamide in acetic acid–ethanol (1: 1) to give methyl 4-aryl-2-{[4-(carbamimidoylsulfamoyl)phenyl]amino}-4-oxobut-2-enoates which were found to exist in solution as mixtures of Z and E isomers.     

Polyfunctional imidazoles: XIII.<Superscript>1</Superscript> Addition and cyclization reactions of 1-aryl-4-chloro-5-(2-nitroethenyl)-1<Emphasis Type="Italic">H</Emphasis>-imidazoles with sulfur and nitrogen nucleophiles

1-Aryl-4-chloro-5-(2-nitroethenyl)-1H-imidazoles reacted with thiols and aromatic amines via Michael addition to give 5-[(1-arylsulfanyl)-2-nitroethyl)]-4-chloro-1H-imidazoles and N-[1-(1-aryl-4-chloro-1H-imidazol-5-yl)-2-nitroethyl]anilines, respectively. [2 + 3]-Cycloaddition of the title compounds to sodium azide afforded 4-(4-chloro-1H-imidazol-5-yl)-1H-1,2,3-triazoles.     

Cyclocondensation of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazol-5-amine

Reactions of N-aryl-3-oxobutanethioamides with 1H-1,2,4-triazole-5-amine give mixtures of 7-arylamino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidines, 5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-thione, 7-methyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-5-thione, and 5-arylamino-7-methyl[1,2,4]triazolo[ 1,5-a]pyrimidines whose ratio depends on the substituent in the aryl group of initial N-aryl-3-oxobutanethioamide and solvent nature (the presence of a proton-donor solvent).     

Cross-recyclization of 4-aryl-2,6-diamino-4<Emphasis Type="Italic">H</Emphasis>-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene: New route to 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-[1]pyrindine-3-carbonitriles and their derivatives

Reaction of 4-aryl-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene led to the formation of 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1H-[1]pyrindine-3-carbonitriles used in the synthesis of substituted 2-alkylsulfanyl-4-aryl-6,7-dihydro-5H-[1]pyrindine-3-carbonitriles and 3-amino-4-aryl-6,7-dihydro-5H-cyclopenta[bthieno[3,2-e]pyridines.     

Three-component heterocyclization of 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 aldehydes and amino acids

Previously unknown substituted 4-aryl-2,7,9-triazaspiro[4.5]decane-6,8,10-triones were synthesized in 50–70% yield by heating 5-(arylmethylidene)barbituric acids with N-methyl- or N-phenylglycine and para-formaldehyde or 4-methoxybenzaldehyde in boiling toluene for 14 h.