Síntese e elucidação estrutural de 1,3,4-oxadiazóis

Abstract

The heterocycles constitute an important building block widely used in Organic Synthesis. Its synthesis has increased because it presents potential therapeutic activities. 1,3,4-oxadiazoles are five-membered heterocycles that exhibit innumerable biological activities. The methodology, normally used for the synthesis of this compound is using hydrazine monohydrate or hydrazine dihydrochloride. The reaction to obtain 1,3,4-oxadiazole occurs between the hydrazides and acids in the presence of a dehydrating agent. In this sense, the present work aims at the synthesis of 1,3,4-oxadiazol derivatives using 2-hydroxybenzohydrazide as intermediate compound. Two methods were used to obtain the hydrazides: a) method A, which traditionally refers to the hydrazolysis reaction; and b) Method B, which consists of the reaction of hydrazine dihydrochloride - a more accessible reagent - and a weak base in an alcoholic medium and the ester. In this work three hydrazides were synthesized - two already mentioned in the literature - with greater yields and an unprecedented one. For the synthesis of the final products, 2-hydroxybenzohydrazide was reacted with two acids: 3-sulfanylpropanoic acid and glycolic acid, both in the presence of POCl3 and 1,4-dioxane as solvent. The hydrazides obtained by method A were obtained in yields ranging from 27.4-83% at reflux, whereas for the B method only the reactions with methyl lactate and methyl salicylate were performed, with yields varying from 81.6 - 95%, respectively. The synthesis of 2- [5- (2-sulfanylethyl) -1,3,4-oxadiazol-2-yl] phenol yielded 36%. 2- [5- (hydroxymethyl) -1,3,4-oxadiazol-2-yl] phenol was obtained in reflux and microwave irradiation in yields ranging from 14.8-26.12% respectively. All compounds were purified by recrystallization or column chromatography and characterized by infrared and nuclear magnetic resonance of hydrogen and carbon-13.