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.     

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.     

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.     

Synthesis of 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids

Nitration of 2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one gave its 5-nitro derivative which was subjected to alkylation with dimethyl sulfate, diethyl sulfate, and benzyl(dimethyl)phenylammonium chloride. The resulting 1,3-dimethyl-, 1,3-diethyl-, and 1,3-dibenzyl-5-nitro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones were reduced to the corresponding 1,3-dialkyl-5-amino-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones, and the latter reacted with itaconic acid to produce 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids. 1-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acid was obtained by analogous reaction with 5-amino-2,3-dihydro-1H-imidazo[4,5-b]-pyridin-2-one.     

Synthesis of isoxazole derivatives of 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole

Cyclocondensation of pent-1-en-4-yn-3-one with phenylhydrazine and p-tolylhydrazine occurs at the positions 1, 3. Proceeding from the 1-aryl-3-ethynyl-4,5-dihydro-1H-pyrazoles formed in the reaction in yields up to 95% we prepared potentially biologically active isoxazole derivatives of pyrazoline. The structure of 5-[1-(4-methylphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-3-phenyl-1,2-oxazole was studied by X-ray diffraction analysis.     

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.     

Fusion of 2-(furan-2-yl)thiazole to 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-benzimidazole

Methylation of 5(6)-nitro-1H-benzimidazole with methyl iodide in the presence of potassium hydroxide and N-methylpyrrolidin-2-one gave a mixture of isomeric 1-methyl-5-nitro- and 1-methyl-6-nitro-1H-benzimidazoles which were reduced with tin in concentrated aqueous HCl on heating. The resulting amines reacted with furan-2-carbonyl chloride in N-methylpyrrolidin-2-one to give furan-2-carboxamides which were treated with excess P₂S₅ in pyridine. Oxidation of isomeric furan-2-carbothioamides with K₃[Fe(CN)₆] in alkaline medium afforded a mixture of intramolecular cyclization products, 2-(furan-2-yl)-6-methyl-6H-imidazo[4,5-g][1,3]benzothiazole and 2-(furan-2-yl)-8-methyl-8H-imidazo[4,5-g][1,3]benzothiazole which were separated by column chromatography and identified.     

3-(4,5-Dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-ylmethyl)oxazolidines and 3-(4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-ylmethyl)perhydro-1,3-oxazines

3-(4,5-Dihydro-1H-pyrazol-1-ylmethyl)oxazolidines and 3-(4,5-dihydro-1H-pyrazol-1-ylmethyl)perhydro-1,3-oxazines were synthesized in 54–85% yield by reactions of α-amino alcohols and 3-aminopropan-1-ol, respectively, with formaldehyde and 4,5-dihydro-1H-pyrazoles.     

<Emphasis Type="Italic">N</Emphasis>-acylimino-substituted 2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes in the synthesis of 3-(1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazol-3-yl)-3<Emphasis Type="Italic">H</Emphasis>-pyrrole-4-carbonitriles

Reaction with phenylhydrazine of 3Н-pyrroles spirobound to a furan ring, N-acylimino-substituted 2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes, occurs with a diasteroselective formation of previously unknown derivatives of 1,2,4-triazole: 5-amino-3-(5-alkyl-1-phenyl-1H-1,2,4-triazol-3-yl)-2-morpholin-4-yl-3H-pyrrole-4-carbonitriles.     

New derivatives of 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole, 4,5-dihydro-1,2-oxazole,and pyrimidine prepared proceeding from (<Emphasis Type="Italic">E</Emphasis>)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one

Condensation of acetylferrocene with 5-phenyl(4-methylphenyl)-1,2-oxazole-3-carbaldehydes afforded (Е)-3-[5-phenyl(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-ones. Reactions of (Е)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one with semicarbazide, thiosemicarbazide, and hydroxylamine led to the formation of 5-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-3-ferrocenyl-4,5-dihydro-1H-pyrazole- 1-carboxamide, 5-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-3-ferrocenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide, and 5-(4-methylphenyl)-3'-ferrocenyl-4',5'-dihydro-3,5'-bi-1,2-oxazole respectively. Reactions of (Е)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one with guanidine and thiourea result in 4-[5-(4-methyl-phenyl)-1,2-oxazol-3-yl]-6-ferrocenylpyrimidin-2-amine and -2-thione respectively.     

Regioselectivity in the reactions of <Emphasis Type="Italic">N</Emphasis>-(polychloroethylidene)-sulfonamides with 1<Emphasis Type="Italic">H</Emphasis>-pyrrole and 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrole

N-(2,2,2-Trichloroethylidene)arenesulfonamides react with 1H-pyrrole and 1-methyl-1H-pyrrole to give the corresponding N-[2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethyl]arenesulfonamides. The reaction of N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide with pyrrole leads to a mixture of 2-mono-and 2,5-disubstituted pyrroles, whereas in the reaction with 1-methyl-1H-pyrrole only the 2-substituted compound is formed. N-(2,2-Dichloro-2-phenylethylidene)-4-methylbenzenesulfonamide reacts with 1H-pyrrole to form N-[2,2-dichloro-2-phenyl-1-(1H-pyrrol-2-yl)ethyl]-4-methylbenzenesulfonamide, and its reaction with 1-methyl-1H-pyrrole gives a mixture of 2-and 3-monosubstituted derivatives. The results of quantum-chemical calculations of the initial reactants and products indicate that the process is orbital-controlled. A good agreement is observed between the experimental data and theoretical conclusions concerning the dependence of the reaction regioselectivity on the nature of substituents in the electrophile molecule.     

Synthesis of 1-[4-(1,3-diaryl-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-5-yl)-2,3,5,6-tetrafluorophenyl]piperidin-4-ols and their acrylates

(4-Hydroxypiperidin-1-yl)tetra- and -octafluorochalcones reacted with phenylhydrazine in acetic acid to give mixtures of polyfluoro-1,3,5-triaryl-4,5-dihydro-1H-pyrazoles and their O-acetyl derivatives. Analogous reactions in ethanol afforded in satisfactory yields 1-[4-(1,3-diaryl-4,5-dihydro-1H-pyrazol-5-yl)-2,3,5,6-tetrafluorophenyl]piperidin-4-ols which were treated with acryloyl chloride to obtain the corresponding acrylates that are promising as monomers for the preparation of fluorescent films.     

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.     

Aqueous hydrolysis of 3-[2-(3-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)-ethylamino]-and 3-[2-(5-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)ethylamino]-propanoates

Noncatalytic hydrolysis of methyl 3-[2-(3-methyl-1H-pyrazol-1-y)ethylamino]-and methyl 3-[2-(5-methyl-1H-pyrazol-1-yl)ethylamino]propanoates at 200°C was performed. According to X-ray diffraction data, the resulting acids exist exclusively as salts.     

Synthesis of ditopic ligands containing bis(1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)-methane fragments

New approaches have been proposed for the synthesis of compounds containing two bis(1H-pyrazol-1-yl)methane fragments. Nucleophilic replacement of the halogen atoms in appropriate tetrabromo derivatives by pyrazoles in the superbasic system KOH-DMSO gave ditopic chelating ligands: 1,1,2,2-tetrakis(1H-pyrazol-1-yl)ethane, 1,4-bis[bis(1H-pyrazol-1-yl)methyl]benzene, and 1,4-bis[bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl]benzene. 1,4-Bis[bis(1H-pyrazol-1-yl)methyl]benzene was also synthesized by reaction of 1H-pyrazole with terephthalaldehyde in the presence of thionyl chloride. 1,1,2,2-Tetrakis(1H-pyrazol-1-yl)ethane was converted into the corresponding tetraiodo and tetranitro derivatives.     

Microwave assisted synthesis of substituted (<Emphasis Type="Italic">Z</Emphasis>)-2-{[1-phenyl-3-(thiophen-2-yl)-1<Emphasis Type="Italic">H</Emphasis>-pyrazol- 4-yl]methylene}benzofuran-3(2<Emphasis Type="Italic">H</Emphasis>)-ones and their antimicrobial activity

Aurones, pyrazole and thiophene scaffolds are known for their potential antimicrobial activity. Herein, we have synthesized hybrid compounds containing three substituted (Z)-2-{[1-phenyl-3-(thiophen-2-yl)- 1H-pyrazol-4-yl]methylene}benzofuran-3(2H)-ones that had been produced from substituted (E)-1-(2-hydroxyphenyl)- 3-[1-phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-yl]prop-2-en-1-ones in high yields. All synthesized compounds were tested in vitro for their antimicrobial activity. Several of those demonstrated promising activity against some fungal and bacterial strains.     

Cyclization of trifluoro-<Emphasis Type="Italic">N</Emphasis>-(prop-2-yn-1-yl)methanesulfonamides to <Emphasis Type="Italic">N</Emphasis>-(hydroxymethyl)-1,2,3-triazoles

Three-component heterocyclizations of trifluoro-N-(prop-2-yn-1-yl)methanesulfonamide, trifluoro-N-pheny-N-(prop-2-yn-1-yl)methanesulfonamide, and trifluoro-N,N-di(prop-2-yn-1-yl)methanesulfonamide with formaldehyde and sodium azide afforded N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-, N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-N-phenyl-, and N,N-bis{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}trifluoromethanesulfonamides as the major products together with minor 1-(hydroxymethyl)-1H-1,2,3-triazole isomers.     

Features of Reaction of 2-(5-Methyl-2-phenyl-2<Emphasis Type="Italic">H</Emphasis>-1,2,3-diazaphosphol-4-yl)-4<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">e</Emphasis>]-1,3,2-dioxaphosphorin-4-one with 1,2-Dicarbonyl Compounds

2-(5-Methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-4H-benzo[e]-1,3,2-dioxaphosphorin-4-one reacts with perfluorodiacetyl, 3,6-di(tert-butyl)-1,2-benzoquinone and phenanthrenequinone only with the participation of a three-coordinated phosphorus atom to form spirophosphoranes containing acyclic 5-methyl-2- phenyl-2H-1,2,3-diazaphosphol-4-yl substituent, whereas the interaction with tetrachloro-1,2-benzoquinone proceeds via expanding the six-membered heterocycle to the nine-membered one to form 2-(2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-2,9-dioxo-4,5,6,7-tetrachlorodibenzo[d,h]-1,3,8-trioxaphosphonine.     

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.     

Synthesis of 2-(3,4,5-trimethoxybenzoyl)-4(5)-phenyl-1<Emphasis Type="Italic">H</Emphasis>-imidazole

The condensation of (2E)-N-hydroxy-2-hydroxyimino-2-phenylethanamine with 3,4,5-trimethoxyphenylglyoxal afforded (1-hydroxy-5-phenyl-1H-imidazol-2-yl)phenylmethanone which reacted with trimethyl phosphite or chloroacetone to give 2-(3,4,5-trimethoxybenzoyl)-4(5)-phenyl-1H-imidazole.