Synthesis and properties of ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-3-carboxylates

Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates reacted with phenylhydrazine to give the corresponding hydrazones, ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1H-pyrazole-3-carboxylates, which were converted to ethyl 1′-aryl-4-formyl-5′-methyl-1-phenyl-1H,1′H-3,4′-bipyrazole-3′-carboxylates by treatment with the Vilsmeier–Haack reagent. No indole derivatives were formed from the same hydrazones under the Fischer reaction conditions, but cyclization to 2-aryl-3,4-dimethyl-6-phenyl-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-ones was observed.     

Synthesis and reactions of 3-(3-ethoxycarbonyl-1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)propenic acid

The reaction of ethyl 4-formyl-1-phenyl-1H-pyrazole-3-carboxylate with the malonic acid led to the formation (2E)-3-(3-ethoxycarbonyl-1-phenyl-1H-pyrazol-4-yl)propenic acid. In reactions of this acid chloride with 4-amino-5-aryl(hetaryl)-4H-1,2,4-triazole-3-thiols were obtained ethyl 4-[(E)-2-{3-aryl(hetaryl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl}ethenyl]-1-phenyl-1H-pyrazoe-3-carboxylates, with 5-aryltetrazoles, ethyl 4-[(E)-2-(5-aryl-1,3,4-oxadiazol-2-yl)-ethenyl]-1-phenyl-1H-pyrazole-3-carboxylates, with 1-(2-hydroxy-3,5-dimethylphenyl) followed by the Baker-Venkataraman rearrangement and the cyclization, ethyl 4-[(E)-2-(6,8-dimethyl-4-oxo-4Hchromen-2-yl)ethenyl]-1-phenyl-1H-pyrazole-3-carboxylate.     

Reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with arylhydrazines. synthesis of isomeric 5-arylcarbamoyl-4-aroyl- and 5-aryl-4-aryloxamoyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazoles

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with arylhydrazines to give methyl 3-aroyl-1-aryl-2-(2-arylhydrazinyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent thermal recyclization into isomeric methyl 1-aryl-5-(arylcarbamoyl)-4-aroyl-1H-pyrazole- 3-carboxylates and methyl 1,5-diaryl-4-[2-oxo-2-(arylamino)acetyl]-1H-pyrazole-3-carboxylates.     

Synthesis of new 1-(3,4-dimethylphenyl)-1,5-dihydropyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4-one derivatives

New substituted pyrazolo[3,4-d]pyrimidin-4-ones have been synthesized as a result of a series of transformations including hydrolysis of ethyl 5-amino-1H-pyrazole-4-carboxylates, cyclization of the carboxylic acids thus obtained to pyrazolo[3,4-d][1,3]oxazin-4(1H)-ones, and treatment of the latter with substituted anilines. The final pyrazolo[3,4-d]pyrimidin-4-one derivatives can also be synthesized from 5-(arylamido)-1H-pyrazole-4-carboxylic acids in the presence of a catalytic amount of anhydrous zinc(II) chloride.     

Chemistry of iminofurans: XIII. Recyclization of 4-arylamino-2-<Emphasis Type="Italic">tert</Emphasis>-butyl-5-oxo-2,5-dihydrofuran-2-yl acetates with ethyl cyanoacetate

Recyclization of 4-arylamino-2-tert-butyl-5-oxo-2,5-dihydrofuran-2-yl acetates with ethyl cyanoacetate in the presence of triethylamine afforded the corresponding ethyl 2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-1H-4,5-dihydropyrrole-3-carboxylates.     

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.     

Reactions of 2,3-dioxopyrrolo[2,1-<Emphasis Type="Italic">a</Emphasis>]isoquinolinecarboxylic acid esters and amides with nitrogen-centered nucleophiles

Reactions of ethyl 2,3-dioxopyrrolo[2,1-a]isoquinoline-1-carboxylates with active nitrogen-centered nucleophiles (phenylhydrazine, hydroxylamine, and benzylamine) involve opening of the pyrrole ring with formation of 2-(3,3-dimethyl-1,2,3,4-tetrahydroisoquinolin-1-ylidene)-N′¹,N′⁴-diphenyl-3-(2-phenylhydrazono) succinohydrazide, 5-(6,7-dimethoxy-3,3-dimethyl-1,2,3,4-tetrahydroisoquinolin-1-ylidene)-2,3,4,5-tetrahydro-1H-1,2-oxazine-3,4,6-trione, and ethyl 4-benzylamino-2-(3,3-dimethyl-1,2,3,4-tetrahydroisoquinolin-1-ylidene)-3,4-dioxobutanoate, respectively. Cyclic amides derived from 5,5-dimethyl-2,3-dioxo-2,3,5,6-tetrahydropyrrolo[2,1-a]isoquinoline-1-carboxylic acid react with benzylamine in a similar way. Reactions of the title compounds with weaker nucleophiles, such as semicarbazide and thiosemicarbazide, are not accompanied by opening of the pyrrole ring, and the products are the corresponding semicarbazones and thiosemicarbazones at the C²=O carbonyl group.     

Three-Component Spiro Heterocyclization of Pyrrolediones with Malononitrile and Cyclic Enols

Ethyl 4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates reacted with malononitrile and five-membered cyclic enols, indan-1,3-dione and cyclopentane-1,3-dione to give 1-substituted ethyl 2-amino-3- cyano-2′,5-dioxo-5′-phenyl-1′,2′-dihydro-5H-spiro[indeno[1,2-b]pyran-4,3′-pyrrole]-4′-carboxylates and ethyl 2-amino-3-cyano-2′,5-dioxo-5′-phenyl-1′,2′,6,7-tetrahydro-5H-spiro[cyclopenta[b]pyran-4,3′-pyrrole]-4′-carboxylates, respectively.     

Thermal and acid-catalyzed transformations of 3<Emphasis Type="Italic">H</Emphasis>-pyrazoles obtained from diphenyldiazomethane and methyl phenylpropiolate

Reaction of diphenyldiazomethane with methyl phenylpropiolate in diethyl ether alongside the expected methyl triphenyl-3H-pyrazole-4-and-5-carboxylates (I and II) (38 and 24%) gave rise also to 8% of methyl 3,5-diphenyl-1-(1-ethoxyethyl)-1H-pyrazole-4-carboxylate. The main thermolysis product obtained from 4-methoxy-carbonyl derivative I was methyl 1,3,5-triphenyl-1H-pyrazole-4-carboxylate, whereas from regioisomer II formed predominantly methyl 4,4,5-triphenyl-4H-pyrazole-3-carboxylate and 1-methoxycarbonyl-2,3,3-triphenylcyclopropene that was a minor product of 3H-pyrazole I thermolysis. Addition of concn. H₂SO₄ to the solutions of methyl triphenyl-3H-pyrazole-4-and-5-carboxylates in AcOH resulted in fast regioselective isomerization of the 3H-pyrazole derivatives into the corresponding 4H-pyrazoles.     

Reactions of Ethyl 2-Amino-5-(2-aryl-2-oxoethylidene)- 4-oxo-4,5-dihydrofuran-3-carboxylates and 2-Amino-5-(2-aryl- 2-oxoethylidene)-4-oxo-4,5-dihydrofuran-3-carbonitriles with Alcohols

Ethyl 2-amino-5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carboxylates and 2-amino- 5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carbonitriles reacted with alcohols in the presence of a catalytic amount of concentrated aqueous HCl to give the corresponding 5-alkoxy-2-amino-5-(2-aryl-2- oxoethyl)-4-oxo-1H-4,5-dihydrofuran-3-carboxylic acid derivatives. A probable reaction mechanism was proposed on the basis B3LYP/6-311G(d) quantum chemical calculations.     

Recyclization of Pyrrolediones with Arylaminoindenones. Synthesis of Indeno[1,2-<Emphasis Type="Italic">b</Emphasis>]pyridines

Dimethyl 1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates reacted with 3-arylamino-1H-inden-1-ones to give the corresponding methyl 1-aryl-3-[2-(arylamino)-2-oxoacetyl]-2,5-dioxo-2,5-dihydro-1H-indeno[1,2-b]pyridine-4-carboxylates.     

4-Aryl-3-(methanesulfonyl)pyrazolo[5,1-<Emphasis Type="Italic">c</Emphasis>][1,2,4]triazines and their transformations

Coupling of 3-alkyl-4-aryl-1H-pyrazole-5-diazonium chlorides with methylene-active methyl phenacyl sulfones afforded new pyrazolo[5,1-c][1,2,4]triazine derivatives via cyclization of the corresponding intermediate 1-aryl-2-(hetarylhydrazinylidene)-2-(methanesulfonyl)ethanones. The reactivity of the methanesulfonyl group on C³ of pyrazolo[5,1-c][1,2,4]triazines toward some nucleophiles was studied.     

Chemistry of Acyl(imidoyl)ketenes: IX. Synthesis and Thermolysis of 3-Aroyl-8-chloro-1,2-dihydro-4<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">c</Emphasis>][1,4]benzoxazine-1,2,4-triones

Reactions of 3-Z-aroylmethylene-6-chloro-3,4-dihydro-2H-1,4-benzoxazine-2-ones with oxalyl chloride afford 3-aroyl-8-chloro-1,2-dihydro-4H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones and Z-3-(2-aryl-2-chlorovinyl)-6-chloro-2H-1,4-benzoxazine-2-ones. Aroyl(imidoyl)ketenes generated by decarbonylation of pyrrolobenzoxazinetriones undergo dimerization through [4+2]-cycloaddition to form 4-aroyl-3-aroyloxy-2-(2-oxo-2H-1,4-benzoxazin-3-yl)-1H, 5H-pyrido[2,1-c][1,4]benzoxazine-1,5-diones.     

Five-membered 2,3-dioxo heterocycles: LV. Reaction of methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with ethyl 3-arylaminobut-2-enoates

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with ethyl 3-aryl-aminobut-2-enoates to give the corresponding ethyl 1,7-diaryl-4-aroyl-3-hydroxy-8-methyl-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-9-carboxylates.     

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.     

Synthesis,structure, and antimicrobial activity of methyl (4-alkanoyl-1,5-diaryl-2-hydroxy-3-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrol-2-yl)acetates

Reactions of methyl 3,4,6-trioxoalkanoates (3,4-dihydroxy-6-oxo-2,4-alkadienoates) with mixtures of aromatic aldehydes and arylamines or with the corresponding N-(arylmethylidene)anilines afforded methyl (4-alkanoyl-1,5-diaryl-2-hydroxy-3-oxo-2,3-dihydro-1H-pyrrol-2-yl)acetates. The product structure was discussed on the basis of their IR, ¹H NMR, and mass spectra and X-ray diffraction data, and their antimicrobial activity against Staphylococcus aureus P-209 and Escherichia coli M₁₇ was evaluated.     

Synthesis of substituted 4-([1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]-[1,3,4]thiadiazol-6-yl)quinolines

4-Amino-5-R¹-4H-1,2,4-triazole-3-thiols react with 2-R²-6-R³-quinoline-4-carboxylic acids in phosphoryl chloride to give 2-R²-6-R³-4-(3-R¹-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)quinolines.     

Chemistry of 1,5-diketones: V. Hydrazination of acyclic and heterocyclic (poly)carbonyl compounds

Reactions of 2-(1-aryl-3-oxo-3-phenylpropylidene)-3,4-dihydronaphthalen-1(2H)-ones, 3-(1-aryl-3-oxo-3-phenylpropyl)-3,4-dihydro-2H-chromene-2,4-diones, and 3,3'-(arylmethylene)bis(3,4-dihydro-2H-chromene-2,4-diones) with hydrazine hydrate have been studied. Depending on the substrate structure, these reactions involve intramolecular heterocyclization with participation of the exocyclic double bond and sidechain carbonyl group or both oxo groups to give new pyrazole, indazole, and diazepine derivatives, as well as hydrazones.     

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.     

Transformations of 3-alkyl-4-(methoxyphenyl)-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-5-diazonium salts

The coupling of 3-alkyl-4-(methoxyphenyl)-1H-pyrazole-5-diazonium salts with acetylacetone followed by cyclization of the formed heterylhydrazones resulted in pyrazolo[5,1-c][1,2,4]triazines. The 4-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrazole-5-diazonium salt was not involved into a similar reaction but suffered an intramolecular azo coupling giving pyrazolo[3,4-c]-cinnoline.