Conselho Nacional de Desenvolvimento Científico e Tecnológico / This work initially describes the regioselective synthesis of a series of 3-alkyl(aryl/heteroaryl)-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole-1-carbohydrazides (2) from the monocyclocondensation reaction of 4-alkyl(aryl/heteroaryl)-1,1,1-trifluoro-4-methoxy-3-alken-2-ones (1), where alkyl= Me, aryl= Ph, 4-MePh, 1-Naphthyl, heteroaryl= Fur-2-yl, Thien-2-yl, with carbohydrazide. The resulting pyrazolyl carbohydrazides (2) were obtained in good yields (62 92 %) when the reactions were performed in ethanol as solvent at 25 ° C in reaction times of 18 20 hours in the molar ratio of 1:1. In subsequent reaction step, a novel series of semicarbazones (3) derived from initial pyrazolyl carbohydrazides (2) was obtained from the condensation reaction of 3-alkyl(aryl/heteroaryl)-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole-1-carbohydrazides (2) with aryl/ heteroaryl substituted aldehydes or acetophenone. The semicarbazones (3) were isolated in yields of 52 97 % when the reaction was conducted in ethanol solvent, at temperature of 60 ° C, in reaction time of 7 hours.
Secondly, aiming the synthesis of non symmetrical bis-pyrazoles systems, were performed reactions involving 5-trifluoromethyl-3-phenyl-5-hydroxy-4,5-dihydro-1H-pyrazole-1-carbohydrazide (2b) and 2,4-pentanedione. These reactions led to the isolation of ethyl 5-trifluoromethyl-3-phenyl-5-hydroxy-4,5-dihydro-1H-pyrazole-1-carboxylate (6b) and 3,5-dimethyl-1H-pyrazole (7) simultaneously, ando not to the bis-pyrazole system theoretically predicted.
Finally, we have tested a cleavage reaction of the carbonyl compound 1,1 -carbonyl-bis-[3-(4-tolyl)-5-trifluoromethyl-1H-pyrazole] (8c), which was, obtained by the bicyclization reaction of 1,1,1-trifluoro-4-(4-tolyl)-4-methoxy-3-buten-2-one (1c) with 1,3-diaminoguanidine hydrochloride. So, the reaction of 8c with phenylhydrazine and hydroxylamine hydrochloride led to the synthesis of 3-(4-tolyl)-5-(trifluoromethyl)-1H-1-phenyl pyrazole and 5-hydroxy-3-(4-tolyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole, respectively. In addition, the series of 3-alkyl(aryl/heteroaryl)-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole-1-carbohydrazides (2) and the novel semicarbazones (3) were evaluated for antimicrobial activity and antioxidant potential. As the result, only concentrations greater or equal than 125 μg/mL inhibited the growth of tested bacteria and fungi and, through the test of antioxidant activity, by the DPPH method, qualitatively and quantitatively, it was observed that all substances provided activity as trappers of the stable free radical DPPH. The compounds were characterized by 1H and 13C {1H} NMR Spectroscopy, Gas Chromatography coupled to Mass Spectrometry (GC-MS), Infrared Spectroscopy (IR), X-Ray Diffraction and their purity determined by CHN Elemental Analysis. / A presente dissertação descreve inicialmente a síntese regiosseletiva de uma série de 3-alquil(aril/heteroaril)-5-trifluormetil-5-hidróxi-4,5-diidro-1H-pirazolil-1-carboidrazidas (2) a partir da reação de monociclocondensação de 4-alquil(aril/heteroaril)-1,1,1-triflúor-4-metóxi-3-alquen-2-onas (1), onde alquil = Me, aril= Ph, 4-MePh, 1-naftil, heteroaril= 2-furil, 2-tienil com carboidrazida. As pirazolil carboidrazidas resultantes (2) foram obtidas em bons rendimentos (62 92 %) quando as reações foram executadas em etanol como solvente, à temperatura de 25 ºC, em tempos reacionais de 18 a 20 horas, na proporção molar de 1:1 entre os reagentes.
Em passo reacional subsequente, uma nova série de semicarbazonas (3) derivadas das pirazolil carboidrazidas iniciais (2) foi obtida a partir de reações de condensação de 3-alquil(aril/heteroaril)-5-trifluormetil-5-hidróxi-4,5-diidro-1H-pirazolil-1-carboidrazidas (2) com aldeídos arilícos, heteroarílicos e acetofenona. As semicarbazonas (3) foram isoladas em rendimentos de 52 97 % quando se realizou as reações em meio etanol, à temperatura de 60 °C, em tempo reacional de 7 horas. Finalmente, testou-se reações de clivagem do composto carbonil-1,1 -bis-3-(4-toluil)-5-trifluormetil-1H-pirazol (8c), obtido a partir da reação de biciclização entre 1,1,1-triflúor-4-(4-toluil)-4-metóxi-3-buten-2-ona (1c) e, posteriormente com cloridrato de 1,3 diaminoguanidina. Assim, reação de 8c com fenilhidrazina e cloridrato de hidroxilamina levaram à síntese de 5-trifluormetil-3-(4-toluil)-1H-1-fenilpirazol e 5-trifluormetil-5-hidróxi-3-(4-toluil)-4,5-diidroxi-isoxazol, respectivamente.
Complementarmente, as séries das 3-alquil(aril/heteroaril)-5-trifluormetil-5-hidróxi-4,5-diidro-1H-pirazolil-1-carboidrazidas (2) e das novas semicarbazonas (3) foram avaliadas quanto à atividade antimicrobiana e o potencial antioxidante. Como resultado, somente as concentrações maiores ou iguais a 125 μg/mL inibiram o crescimento das bactérias e fungos testados e através do teste de atividade antioxidante, pelo método DPPH qualitativo e quantitativo, observou-se que todas as substâncias apresentaram atividade como trapeadores do radical livre estável DPPH. Os compostos foram caracterizados por Espectroscopia de RMN de 1H e 13C {1H}, Cromatografia Gasosa acoplada à Espectrometria de Massas (CG-MS), Espectroscopia de Infravermelho (IV), Difração de Raios-X e sua pureza determinada via Análise Elementar CHN.
Secundariamente, visando à síntese de sistemas bis-pirazólicos não simétricos realizaram-se reações envolvendo a 3-fenil-5-trifluormetil-5-hidróxi-4,5-diidro-1H-pirazolil-1-carboidrazida (2b) e a 2,4-pentanodiona. Estas reações conduziram ao isolamento de 3-fenil-5-trifluormetil-5-hidróxi-4,5-diidro-1H-pirazolil-1-carboxilato de etila (6b) e de 3,5-dimetil-1H-pirazol (7) simultaneamente, e não, do sistema bis-pirazólico teoricamente previsto.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufsm.br:1/10470 |
| Date | 16 September 2010 |
| Creators | Cavinatto, Susiane |
| Contributors | Bonacorso, Helio Gauze, Morel, Ademir Farias, Alves, Sydney Hartz |
| Publisher | Universidade Federal de Santa Maria, Programa de Pós-Graduação em Química, UFSM, BR, Química |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFSM, instname:Universidade Federal de Santa Maria, instacron:UFSM |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 100600000000, 400, 500, 300, 500, 500, 06c852ad-d805-43c3-99d6-93a6a86f507c, 3710e6db-704b-49fc-9f37-08fd19553ea0, 22df5f67-c304-4742-b982-4d1e6d30aecc, d222d3db-5dc1-4604-ac47-2d6968c2c477 |
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