Synthesis of 3,5-disubstituted-1,2,4-oxadiazoles using tetrabutylammonium fluoride as a mild and efficient catalyst

1,2,4-oxadiazole: A Brief Review from the Literature About the Synthesis and Pharmacological Applications

“…Among these stand out: low income, long reaction time (6 -12h), difficult purification and formation of byproducts, such as oxadiazole resulting from amidoxime cyclization. Gangloff et al (2001) reported the use of tetrabutylammonium fluoride (TBAF) as a very efficient catalyst in the cyclization step of the intermediate O-acylated (Scheme 2). According to the authors the reaction occurs under mild conditions of temperature, especially when using one equivalent of TBAF and THF or acetonitrile as solvent.…”

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.…”

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

“…17 The use of tetrabutylammonium fluoride (TBAF) as an activator to promote the cyclization of O-acylamidoximes has been reported. 18 Historically, the preferred method of obtaining O-acylamidoximes is through the reaction of amidoximes with activated carboxylic acid derivatives or with carboxylic acids in the presence of a coupling reagent, such as dicyclohexylcarbodiimide (DCC), 19,20,21 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (EDC), 11,20,22 2-(dimethylamino)isopropyl chloride (DIC)/HOBt, 11 bis-(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl), 20 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU), 23 or 1,1'-carbonyldiimidazole (CDI). 20,24 However, these methods have several drawbacks.…”