Microwave-assisted efficient, one-pot, three-component synthesis of 3,5-disubstituted 1,2,4-oxadiazoles under solvent-free conditions

Green Approach Towards Synthesis of 3-Substituted-5-Carbonylmetyl-1,2,4-Oxadiazoles Without Any Solvent and Catalyst via Transamidoximation.

“…1,2,4-Oxadiazoles have often been used as hydrolysis-resisting bioisosteric replacements for esters and amides 10 and as dipeptide mimetics 11 Bearing in mind the noteworthy relevancies in the fields of medicinal, biological and synthetic organic chemistry, there has been marvelous curiosity in developing efficient procedures for the synthesis of 1,2,4-oxadiazoles and quite number of synthetic procedures have been accounted in the literature for the synthesis of 1,2,4-oxadiazoles derivatives, which include the reaction of amidoxime with activated carboxylic acid derivatives such as acid chlorides, 12 fluorides, 13 anhydrides (BOP-Cl), 14 or active esters 15 using coupling reagents like, DCC, 16 DIC/HOBt, 17 TBTU, 18 CDI. 19 Besides this, metal catalysts, 20 TBAF, 21 microwave technique, 22 NaH, 23 NaOMe, 24 K 2 CO 3 25 and condensation of malonic diesters with amidoximes under neutral and solvent-free conditions 26 were also reported. However, most of the synthetic protocols reported so far experienced from several difficulties, such as the obligation of drastic reaction conditions (strong acids, high temperatures), prolonged reaction time, use of toxic and expensive reagents, use of hazardous solvents and catalysts, formation of by-products which resulted in poor yields of the desired target product.…”

Unexpected Coordination Behaviour of 3,5‐Di(2‐pyridyl)‐1,2,4‐oxadiazole

“…Nowadays 3,5-substituted 1,2,4-oxadiazoles are usually prepared from amidoxime precursors, by reacting them with O-acylating agents like acyl chlorides, [20] aldehydes, [21] trichloroalkanes [22] or carboxylic acids in combination with coupling agents, [23] followed by cyclodehydration [Scheme 2 (a)]. For the preparation of symmetrically substituted 3,5-bisaryl-1,2,4-oxadiazoles the self-condensation of amidoximes has been used, which is expected to react via a nitrile intermediate [Scheme 2 (b)].…”

A Convenient Synthesis and Cytotoxic Activity of 3-Aryl-5-Pentyl-1,2,4-Oxadiazoles From Carboxylic Acid Esters and Arylamidoximes Under Solvent-Free Conditions

“…26,27 Microwave irradiation, an efficient and innocuous technique for reagent activation in the synthesis of organic compounds, and in particular heterocyclic compounds, has been applied with success, and was able to generate products in good to excellent yields. 28,29,30,31 The use of microwave irradiation in organic chemistry has being widely explored over the last few years. 32 Two of the main advantages of this technology are the potential for dramatically shortened reaction times and access to reaction conditions that are not attainable with conventional thermal heating.…”