M. V. Vovk

Synthesis and Antimicrobial Activity of Pyrazole-4-carboxylic Acid Hydrazides and N-(4-Pyrazoyl)hydrazones of Aromatic and Heteroaromatic Aldehydes

Proceeding from the fact that some widely used antibacterial preparations (furacilin, furazolidone, ftivazide) contain hydrazone groups, we decided to synthesize a series of pyrazole-4-carboxylic acid hydrazides, modify these compounds so as to obtain N-(4-pyrazoyl)hydrazones, and study the antibacterial properties of the products. Hydrazides IIIa – IIIg were synthesized based on the previously described pyrazole-4-carboxylic chloroanhydrides (Ia – Ig) [1]. Treated with methanol in the presence of an organic base, compounds Ia – Ig converted with a quantitative yield into the corresponding methyl esters IIa – IIg. Interaction of these intermediates with hydrazine hydrate (on heating in ethanol) led to a high yield of hydrazides IIIa – IIIg. The yields and physicochemical characteristics of methyl esters IIa – IIg and hydrazides IIIa – IIIg are listed in Table 1.

Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-d]pyrimidin-4(5H)-ones

Abstract6-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.

4-Functionally Substituted 3-Heterylpyrazoles: III. * 3-Aryl(heteryl)pyrazole-4-carboxylic Acids and Their Derivatives

Abstract3-Aryl(heteryl)-4-formylpyrazoles were cleanly oxidized by potassium permanganate in water-pyridine medium to afford in high yield 3-aryl(heteryl)pyrazole-4-carboxylic acids, that were further converted into the corresponding chlorides and amides.

1-Aryl-1-chloro-2,2,2-trifluoroethylisocyanates—convenient reagents for synthesis of 2-aryl-2-trifluoromethyl-2,3-dihydro-4H-benzo[e][1,3]oxazin-4-ones

Abstract 1-Aryl-1-chloro-2,2,2-trifluoroethylisocyanates react with 3-alkoxyphenols to form N-(1-aryl-2,2,2-trifluoroethylidene)-O-(3-alkoxyphenyl)urethanes, which undergo intramolecular thermal cyclization into derivatives of 2-aryl-2-trifluoromethyl-2,3-dihydro-4H-benzo[e][1,3]oxazin-4-ones.

Polyfunctional imidazoles: I. Synthesis of 1-substituted 4-chloro-1H-imidazole-5-carbaldehydes by Vilsmeier-Haack reaction

Abstract2-[Alkyl(aryl)amino]acetamides in reaction with Vilsmeier-Haack reagent afforded 1-alkyl(aryl)-4-chloro-1H-imidazole-5-carbaldehydes.

4-Functionally Substituted 3-Heterylpyrazoles: IV. 1-Phenyl-3-aryl(heteryl)-5-(4-pyrazolyl)-2-pyrazolines

Abstract3-Aryl(heteryl)-4-formylpyrazoles in condensation with methyl aryl(heteryl) ketones afforded 1-aryl(heteryl)-3-[3-aryl(heteryl)-4-pyrazolyl]propenones. The latter reacted with phenylhydrazine yielding 1-phenyl-3-aryl(heteryl)-5-(4-pyrazolyl)-2-pyrazolines.

Synthesis of new Di-, Tetra-, and hexahydropyrazolo[3,4-e][1,4]diazepine derivatives

Alkaline hydrolysis of 5-(2,2-diethoxyethyl-, aroylmethyl-, or ethoxycarbonylmethyl)-1H-pyrazolo-[3,4-e]pyrimidin-4(5H)-ones gave 5-amino-N-(2,2-diethoxyethyl-, aroylmethyl-, or carboxymethyl)-1H-pyrazole-4-carboxamides which underwent cyclization to the corresponding 7-hydroxy-5,6,7,8-tetrahydropyrazolo-[3,4-e][1,4]diazepin-4(1H)-ones, 5,6-dihydropyrazolo[3,4-e][1,4]diazepin-4(1H)-ones, and 1,5,6,8-tetrahydropyrazolo[3,4-e][1,4]diazepine-4,7-diones. Reduction of the cyclization products with NaBH4 and LiAlH4 afforded 5,6,7,8-tetrahydropyrazolo[3,4-e][1,4]diazepin-4(1H)-ones and 1,4,5,6,7,8-hexahydropyrazolo[3,4-e]-[1,4]diazepines.

4-Functionally Substituted 3-Heterylpyrazoles: XIII. 3-Aryl(heteryl)-4-(4-pyrazolyl)-1,2,3,4-tetrahydropyrimidin-2-ones(thiones)

Cyclocondesation of 3-aryl(heteryl)pyrazole-4-carbaldehydes with ethyl acetoacetate and urea (thiourea) in the presence of FeCl3 · 6H2O afforded 3-aryl(heteryl)-4-(4-pyrazolyl)-1,2,3,4-tetrahydropyrimidin-2-ones(thiones).

A new synthetic access to 2-trihalogenomethyl-3,4-dihydrofuro[2,3-d]-pyrimidin-4-ones

ABSTRACT 2-Amino-5-alkoxycarbonylfurans 1a–c react with 1-chloro-2,2,2-trihalogenoethyliden-O-methylurethanes 2a,b at room temperature to give N-(2-furyl)-N′-methoxycarbonyl-trihalogenoacetamidines 3a–f which cyclize into 2-trihalogenomethyl-3,4-dihydrofuro[2,3-d]pyrimidin-4-ones 4a–f on boiling in toluene.

4-Functionally Substituted 3-Heterylpyrazoles: VIII. 3-Aryl(heteryl)-4-hydroxyl(chloro)methylpyrazoles

Abstract3-Aryl(heteryl)pyrazole-4-carbaldehydes were reduced with sodium tetrahydridoborate under mild conditions to give 3-aryl(heteryl)-4-hydroxymethylpyrazoles which were converted into the corresponding 4-chloromethyl derivatives by treatment with thionyl chloride. The subsequent reaction with triphenylphos- phine led to formation of triphenyl(4-pyrazolylmethyl)phosphonium chlorides, and Wittig reaction of the latter with aromatic or heteroaromatic aldehydes yielded 4-[2-aryl(heteryl)ethenyl]pyrazoles.