M. K. Bratenko

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.

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: 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).

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.

4-Functionally-substituted 3-heterylpyrazoles: XVI. 3-(3-Arylpyrazol-4-yl)propyonic acids

Bromination of 3-(3-arylpyrazol-4-yl)acrylic acids led to the formation of 2-bromo-3-(3-arylpyrazol-4-yl)acrylic acids that were converted into 3-(3-arylpyrazol-4-yl)propynoic acids by treatment of potassium hydroxide with an alcoholic solution.

Functionally substituted 3-heterylpyrazoles: XI. 3-[3-aryl(heteryl)pyrazol-4-yl]propenoic and propanoic acids

Abstract3-Aryl(heteryl)-4-formylpyrazoles by condensation with malonic acid furnish 3-[3-aryl(heteryl)- pyrazol-4-yl]propenoic acids that in the presence of Raney nickel are reduced by hydrazine hydrate to 3-[3-aryl(heteryl)pyrazol-4-yl]propanoic acids. The successive conversion of both type acids into the corresponding acyl chlorides, esters, and amides was performed.

4-Functionally Substituted 3-heterylpyrazoles: XII. 4-Chlorothieno[2,3-c]pyrazole-5-carbonyl Chlorides

Abstract3-(4-Pyrazolyl)acrylic acids reacted with excess thionyl chloride in the presence of benzyltriethylammonium chloride affording 4-chlorothieno[2,3-c]pyrazole-5-carbonyl chlorides which were converted into the corresponding acids, esters, and amides.

4-functionally substituted 3-heterylpyrazoles: XVIII. Intramolecular cyclization of N-[3-(2-Chlorophenyl)-4-pyrazolyl]methylamine and its N-alkyl derivatives into 4,5-dihydro-2H-pyrazolo[4,3-c]quinolines

N-[3-(2-Chlorophenyl)-4-pyrazolyl]methylamine and its N-alkyl-derivatives at heating in DMF in the presence of K2CO3 undergo an intramolecular cyclocondensation yielding 4,5-dihydro-2H-pyrazolo[ 4,3-c]quinolines.

4-Functionally-substituted 3-heterylpyrazoles: XVII. 3-Aryl-1-phenyl-4-pyrazolmethylsulfanyl(sulfinyl, sulfonyl)acetic acids

Abstract3-Aryl-1-phenyl-4-mercaptomethylpyrazoles reacted with monochloroacetic acid to give 3-aryl-1-phenyl-4-pyrazolylmethylsulfanylacetic acids whose oxidation with hydrogen peroxide in acetone or acetic acid solution led to 3-aryl-1-phenyl-4-pyrazolylmethylsulfinyl-and sulfonylacetic acids, respectively.

4-Functionally Substituted 3-Heterylpyrazoles: XIV. N-Benzyl-N-[3-aryl(heteryl)-4-pyrazolylmethylene]amines and Their Derivatives

Reduction with sodium tetrahydridoborate of Schiff bases derived from 3-aryl(heteryl)pyrazole-4-carbaldehydes and benzylamines gave N-benzyl-N-[3-aryl(heteryl)-4-pyrazolylmethylene]amines which were acylated with benzoyl chloride and succinic and maleic anhydrides to obtain the corresponding amides. Treatment of the title compounds with phenyl isothiocyanate afforded substituted thioureas.