Síntese, caracterização e avaliação antimicrobiana de novos heterociclos nitrogenados utilizando como precursores β-alcóxivinil trifluormetil cetonas de cadeias alquílicas longas

Abstract

This work describes the synthesis of 1H-pyrazole-1-thiocarboxamide, thiazol-1H-pyrazol-5-ol, 1H-pyrazol-1-yl-tiazoles and 1-(3-alkyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazol-1-yl)-alquen-1-ones were prepared from 1,1,1-trifluoro-4-methoxy-3-alquen-2-one lipophilic chains substituted (C6-C13) and hydrazides. The precursors 1,1,1-trifluoro-4-methoxy-3-Alquen-2-one [F3CCOCH=C(R)OCH3 where R = C6H13 (3a); C7H15 (3b); C8H17 (3c); C9H19 (3d ), C11H23 (3e); C13H27 (3f), (CH2) 2 Ph (3g)] were obtained in yields of 70-96%, by acylation reaction of the derivatives of the respective dimetoxicetais methyl ketones [2-octanone (1a), 2-nonanona (1b), 2-decanone (1c), 2-undecanone (1d), 2-tridecanone (1e), 2-pentadecanone (1f) and 4-phenyl-2-butanone (1g) with trifluoroacetic anhydride. These precursors 3a-g were cyclocondensed with semicarbazide hydrochloride to form the product 3-alkyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazol-1-carboxamides 4, with yields of 45-68%. The precursors 3a-g were subjected to cyclocondensation reaction with thiosemicarbazide and led to the formation of the series of products 3-alkyl-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-pyrazole-1-thiocarboxamide 5, in yields of 55-82%. This series 5 when reacted with α-bromoacetophenone led to bi-heterocyclic systems alkyl-3-1-(4-phenylthiazol-2-yl)-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazol-5-ol 6 with yield of 71-87% and 2-(3-alkyl-5-trifluoromethyl-1H-pyrazol-1-yl)-4-phenylthiazol 7, with yields of 68-89%. Finally, we investigated the reaction between 1,1,1-trifluoro-4-methoxy-3-alquen-2-one 3f and 3g with hydrazides obtained from natural fatty acids (palmitic, stearic and oleic), which allowed obtaining series of 1-(3-alkyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazol-1-yl)-alquen-1-ones 11f, 12f and 13f which R = C13H27; and 11g, 12g and 13g where R = (CH2)2Ph) with yields of 50-68%. The synthesis of these compounds applied the principles of green chemistry is the replacement of conventional organic solvents for green organic solvents such as ethanol. The compounds of the series 3 to 7 were evaluated for antimicrobial activity. As a result, the minimum inhibitory concentration (MIC) of 0.15 to 1.56 mg/mL inhibited the growth of bacteria and fungi. All synthesized compounds are novel and had their structures assigned by 1H, 13C NMR data and mass spectrometry data.