A review on synthetic routes for obtaining of 2,5-disubstituted 1,3,4-oxadiazoles via cyclodehydration and oxidative cyclization reactions

Abstract

1,3,4-Oxadiazole core is a known pharmacophore fragment, which possesses a wide opportunities for chemical modification and established versatile pharmacological potential. Moreover, oxadiazole plays a vital role in many drug structures and various biologically active compounds. For the construction of 1,3,4-oxadiazole cycle, different synthetic methods can be employed. In particular, the cyclization of N,N′-diacylhydrazines is a very common and convenient way for the synthesis of 2,5-disubstituted 1,3,4-охаdiazoles. This approach includes dehydration followed by simultaneous cyclization of diacylhydrazines under the action of various dehydrating reagents – thionyl chloride, polyphosphoric acid, phosphorus pentoxide, acetic anhydride, phosphorus oxychloride, sulfuric acid etc. Another direction for the synthesis of non-condensed heterocyclic systems based on 1,3,4-oxadiazole is the oxidative cyclization of hydrazide-hydrazones, which are obtained by condensation of carboxylic acids hydrazides with appropriate aldehydes. The oxidizing reagents that are most commonly used in this reaction are potassium permanganate in acetone medium, bromine in acetic acid, Pb3O4, chloramine-T etc. In this review, we attempt to highlight the detailed approaches for obtaining 1,3,4-oxadiazole derivatives based on cyclodehydration and oxidative cyclization reactions as the most commonly used methods of synthesis for this class compounds.