Síntese e atividades antimicrobiana/antioxidante de 5-trifluormetil-5-hidróxi-4,5-diidro-1h-pirazóis 1-(2-naftoxiacetil), 1-fenoxiacetil, 1-tiofenoxiacetil, 1-(n-fenilglicina) substituídos

Abstract

This work describes an efficient approach for the regioselective synthesis of new series of substituted 1-(2-naphthoxyacetyl), 1-phenoxyacetyl, 1-thiophenoxyacetyl, 1-(N-phenylglicine)-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles from the cyclocondensation reactions of 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-trifluoroalk-3- en-2-ones [CF3C(O)CH=CHROMe(Et) where R = H, Me, Ph, 2-furyl, 1-naphthyl] with 2-aryloxyaceto, 2-thiophenoxyaceto, N-phenylglicine hidrazides under synthetic conventional procedures. These methodologies furnished high purity and air-stable products in 34 96 % yields. In a subsequent step, the reactions of dehydration intramolecular of two examples of 5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles, are described. These reactions were carried out in pyridine/benzene in the presence of thionyl chloride and led to the isolation of a series of substituted 1-(2-naphthoxyacetyl)- and 1-phenoxyacetyl-3-phenyl-5-trifluoromethyl-1H-pyrazoles in 82 and 78 % yields respectively. In addition, the series of 5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles were evaluated for antimicrobial activity. As the result, the 1-(N-phenylglicine)-5- trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazol series showed the best activities where the concentrations greater or equal than 100 µg/mL inhibited the growth of tested bacteria (Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli), fungi(Candida albicans e Aspergillus fumigatus) and algae (Prototheca zopfii). Moreover, the test of antioxidant activity demonstrated that 5-trifluoromethyl- 5-hydroxy-4,5-dihydro-1H-pyrazoles non-substituted at position 3 of the pyrazoline ring, of each series, provided positive activity as trappers of the stable free radical DPPH by the qualitative 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The compounds were characterized by 1H and 13C {1H} NMR Spectroscopy, Gas Chromatography coupled to Mass Spectrometry (GC/MS) and their purity determined by CHNS Elemental Analysis.