New trifluoromethyl-containing (E)-N′-arylidene-[3-alkyl(aryl/heteroaryl)-4,5-dihydro-1H-pyrazol-1-yl]carbohydrazides: Synthesis, crystal structure and antimicrobial/antioxidant activity

A new series of twenty-one trifluoromethyl-containing (E)-N′-arylidene-1H-pyrazole-1-carbohydrazides (4) was synthesized by the cyclocondensation reactions of six 3-alkyl(aryl/heteroaryl)-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole-1-carbohydrazides (2) with eleven aryl/heteroaryl aldehydes and acetophenone (3) in 52–97% yields and six new carbohydrazides 2 were easily obtained from the reaction of 1,1,1-trifluoro-4-alkyl(aryl/heteroaryl)-4-methoxy-3-alken-2-ones (1) with carbohydrazide. Subsequently, four examples of carbohydrazides 4 were fully studied by X-ray diffraction and the twenty-seven pyrazolyl-carbohydrazides 2 and 4 screened for their antioxidant and antimicrobial proprieties and evaluated by DPPH and MIC methods, respectively. Both series 2 and 4 showed ability to capture DPPH free radical for IC50 from 47.57 to 487 μg/mL. Most of the compounds presented fungistatic and bacteriostatic activity only for high MIC levels ranging from 0.25 mg/mL to 0.5 mg/mL.

Graphical abstractThe regioselective synthesis and structural study via X-ray diffraction of a series of twenty-seven new (E)-N′-arylidene-(5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazol-1-yl)carbohydrazides with ability to capture DPPH free radical, but showing a weak fungistatic and bacteriostatic activity, is described.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We have developed a convenient route for the regioselective synthesis of new fluorinated carbohydrazides. ► Our method employs β-alkoxyvinyl trifluoromethyl ketones to attach CF3 group at carbohydrazides. ► We propose a procedure with easy of product isolation/purification. ► Our strategy allows the easy insertion of four substituents simultaneously to heterocycle system. ► These trifluoromethylated compounds can be used as intermediates for the synthesis of new drug candidates.