One-pot synthesis of trifluoromethyl- and nitroso-substituted pyrazolines and pyrazoles and their tuberculostatic activity

3-Trifluoromethyl-substituted 4-nitrosopyrazolines and 4-nitrosopyrazoles were prepared by a one-pot synthesis from trifluoromethyl-containing 1,3-diketones, sodium nitrite in acetic acid, and hydrazines (hydrazine hydrate, methylhydrazine). 3-Trifluoromethylpyrazolines can be converted to pyrazoles on heating. The use of phenylhydrazine in these reactions led to the formation of regioisomeric 4-hydroxyimino-5-(trifluoromethyl)pyrazoline. The structure of heterocycles synthesized was established using X-ray diffraction study, ¹H and ¹⁹F NMR spectroscopy. The obtained products exhibited considerable tuberculostatic activity.     

Facile synthesis of 6-organyl-4-(trifluoromethyl)pyridin-2(1H)-ones and their polyfluoroalkyl-containing analogs

The three-component cyclization of 3-polyfluoroalkyl-3-oxopropanoates and methyl ketones with ammonium acetate affords 6-organyl-4-(polyfluoroalkyl)pyridin-2(1H)-ones (organyl is alkyl, aryl, or hetaryl). The synthesized pyridones were evaluated for antifungal, antibacterial, and analgesic activity.

     

Polyfunctional pyrazoles. 1. Synthesis of 3-aryl-1-(2-cyanoethyl)-4-formylpyrazoles and their 3-(5-methylfur-2-yl)-substituted analog

Previously unknown substituted pyrazoles were obtained by the reaction of the 2-cyanoethylhydrazones of aryl methyl ketones and 5-methylfur-2-yl methyl ketone with the Vilsmeier-Haack reagent.Bukovina State Medical Academy, Chernovtsy. Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1219–1221, September, 1999.     

Acyclic analogs of pyrimidine nucleosides. Synthesis of 1-(2-hydroxyethoxymethyl)- and 1-(4-hydroxybutyl)-5-amino derivatives of uracil

With the objective of discovering new antiviral agents based on acyclic analogs of pyrimidine nucleosides, we have synthesized 1-(2-hydroxyethoxymethyl)- and 1-(4-hydroxybutyl) derivatives of uracil having various aromatic and heterocyclic amino-containing substituents in the 5 position of the pyrimidine ring.Scientific-Research Institute of Pharmacology, Volgograd Medical Academy, Volgograd 400066, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 971–978, July, 1998.     

Polyfunctional pyrazoles. 3.* Synthesis of 3-(3-aryl-4-formyl-1-pyrazolyl)propionic acids and their amides

3-(3-Aryl-4-formyl-1-pyrazolyl)propionic acids were synthesized by the reaction of 3-aryl-1-(2-cyanoethyl)-4-formylpyrazoles with concentrated hydrochloric acid. They were converted into the corresponding amides by the carbodiimide method.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1483–1486, October, 2004.For Communication 2, see [1].     

Synthesis of 1-(2-aminoethyl)pyrazoles under phase-transfer catalysis

Alkylation of pyrazoles with 2-chloroethylamine was performed under conditions of phasetransfer catalysis. Depending on the substrate acidity, the electrophilic substitution process may be accompanied by dehydrochlorination of the alkylating agent, so that 6 equiv of 2-chloroethylamine should be used in the alkylation of 3,5-dimethylpyrazole.     

Synthesis and Electrochemical Behavior of Some 1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles

Summary. 1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles are key intermediates in obtaining various heterocyclic systems including pyrazolotriazoles. We present the voltammetric behavior of these compounds in nonaqueous media, with the following para substituents grafted on the benzene ring: –N(CH₃)₂, –OH, –OCH₃, –F, –Cl, –CF₃, –NO₂, as well as of the novel compounds with –Br, –I, and –SCH₃ in the para position, in order to elucidate the influence of the various substituents on the mechanism of anodic oxidation.     

Synthesis of 1-(4-butoxyphenyl)-1-cyclohexyl-3-(4-arylpiperazin-1-yl)-2-phenylpropan-1-ols and their dihydrochlorides

Aminomethylation of 1-(4-butoxyphenyl)-2-phenylethanone with paraformaldehyde and substituted piperazines in ethanol medium results in 1-(4-butoxyphenyl)-3-(4-R-piperazin-1-yl)-2-phenylpropan-1-ones. The latter react with cyclohexylmagnesium halide to give 1-(4-butoxyphenyl)-1-cyclohexyl-3-(4-arylpiperazin-1-yl)-2-phenylpropan-1-ols. Reduction of the prepared β-aminoketones with lithium aluminum hydride in absolute diethyl ether leads to the secondary aminopropanols. The prepared compounds could be converted into the corresponding dihydrochlorides.     

Synthesis and structure of 1-(buta-1,3-dien-2-yl)pyrazoles and their behavior in Diels-Alder reactions

A convenient procedure has been developed for the synthesis of cis-and trans-isomeric 1-(buta-1,3-dien-1-yl)-1H-pyrazoles by reaction of the corresponding pyrazoles with β-methylacrolein diethyl acetal and subsequent 1,4-cleavage of the nucleophilic substitution products. The behavior of the title compounds in Diels-Alder reactions with maleic anhydride has been studied. According to the ¹H NMR data, 1-(buta-1,3-dien-1-yl)-1H-pyrazole is a mixture of cis and trans isomers. Butadienylpyrazoles having methyl groups in the pyrazole ring do not react with maleic anhydride.     

1-(1-Carboxy-2-R-4-methylcyclohex-4-enyl)carbonyl- and 1-(2-R-4-Methylcyclohex-4-enyl)carbonyl-3,5-dimethyl(diphenyl)pyrazoles

1-(1-Carboxy-2-R-4-methylcyclohex-4-enyl)carbonyl- and 1-(2-R-4-methylcyclohex-4-enyl)carbonyl-3,5-dimethyl(diphenyl)pyrazoles have been obtained from the reaction of monohydrazides of 2-R-methyl-4-cyclohexen-1,1-dicarboxylic acids and hydrazides of 2-R-4-methyl-4-cyclohexen-1-monocarboxylic acids with acetylacetone and dibenzoylmethane. The conditions for the formation of the pyrazoles depend on the nature of the substituents in the hydrazide starting materials and the structure of the 1,3-diketone used.     

Synthesis of 4-(1-Adamantyl)- and 4-(1-Adamantylmethyl)-substituted Halothiazoles

1-Adamantyl bromomethyl ketone and 1-adamantylmethyl chloromethyl ketone react with potassium thiocyanate in dimethylformamide to give the corresponding thiocyanatoketones which cyclize under the influence of HCl into 4-(1-adamantyl) and 4(-adamantylmethyl)chlorothiazole respectively. 4-(1-Adamantyl)-2-amino-5-bromothiazole and its N-derivative were synthesized by the reaction of 1-adamantyl dibromomethyl ketone with thioureas and N-substituted thiourea in acetonitrile.     

Polyfunctional pyrazoles. 4. Synthesis of 3-[3-aryl-1-(2-ethoxycarbonyl)-4-pyrazolyl]acrylic and-propionic acids

3-(3-Aryl-4-formyl-1-pyrazolyl)propionic acids are converted by Knoevenagel condensation under conditions of microwave activation into 3-[3-aryl-1-(2-ethoxycarbonyl)-4-pyrazolyl]acrylic acids. Reduction of the latter with hydrazine hydrate in the presence of Raney nickel gives 3-[3-aryl-1-(2-ethoxycarbonyl)-4-pyrazolyl]propionic acids. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 686–690, May, 2006.     

Synthesis and fungicidal activity of substituted 2-(4-chlorophenoxy)-1-(3-pyridyl)ethan-1-ols

A series of new substituted 2-(4-chlorophenoxy)-1-(3-pyridyl)ethan-1-ols has been obtained by the interaction of substituted 3-(oxiranyl)pyridines with 4-chlorophenol or sodium 4-chlorophenoxide for pharmacological and agrochemical screening. Fungicidal activity has been shown for the obtained compounds.     

Synthesis and Electrochemical Behavior of Some 1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles

1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles are key intermediates in obtaining various heterocyclic systems including pyrazolotriazoles. We present the voltammetric behavior of these compounds in nonaqueous media, with the following para substituents grafted on the benzene ring: –N(CH₃)₂, –OH, –OCH₃, –F, –Cl, –CF₃, –NO₂, as well as of the novel compounds with –Br, –I, and –SCH₃ in the para position, in order to elucidate the influence of the various substituents on the mechanism of anodic oxidation.     

Synthesis and pharmacological activity of 4-(4'-(chlorophenyl)-4-hydroxypiperidine) derivatives

A new series of 4-(4'-chlorophenyl)-4-hydroxypiperidine derivatives (2-5), substituted at nitrogen, were synthesized and tested as potential analgesic compounds as well as evaluated for their effect on hypotensive activity. Results showed that all the derivatives exhibit significant analgesic activity in male Wistar rats at a dose of 50 mg/kg of body weight after intramuscular injection, when tested by thermal stimuli (tail flick test). Pethidine was used as reference drug. Compounds 2, 3 and 5 produced reduction in blood pressure in normotensive rat.     

Synthesis and antibacterial activity of 1-(2,4-dichlorobenzoyl)-4-substituted thiosemicarbazides, 1,2,4-triazoles and their methyl derivatives

A series of 1-(2,4-dichlorobenzoyl)thiosemicarbazides, s-triazoles and their methyl derivatives have been synthesised by condensation of 2,4-dichlorobenzoyl hydrazine with aryl isothiocyanates. Subsequent ring closure of the substituted thiosemicarbazides yielded the s-triazoles, and reaction with methyl iodide resulted methyl derivatives. All the compounds were subjected to in vitro testing against two gram-positive and two gram-negative bacteria. Antibacterial activity was found to be moderate to good in most of the compounds.     

Synthesis and reactivity of new l-(1-adamantyl)pyrazoles

Using 1-adamantylhydrazine as starting material, a series of 1-(1-adamantyl)pyrazoles has been prepared. Electrophilic reactivity (bromination and nitration) and nucleophilic reactivity (quaternarization) have been studied. Proton nuclear magnetic resonance spectra of all the new compounds are recorded.