A Mild and Efficient One‐Pot Preparation of 1,2,4‐Oxadiazoles from Nitriles and Carboxylic Acids Using Vilsmeier Reagent

Abstract

A one-pot synthesis of 1,2,4-oxadiazoles has been achieved from the corresponding amidoximes and carboxylic acids or from nitriles, hydroxylamine and carboxylic acids, employing the OH activation property of the Vilsmeier reagent. The precursor O-acylamidoxime could be derived in situ which underwent an intramolecular cyclization in the presence of Vilsmeier reagent to afford 1,2,4-oxadiazole. The products were simply obtained in good to excellent yields under mild condition and compatible with a range of functional groups. Utilization of easy workup and purification of products make it very interesting.

Synthesis, Antitumor and Cytotoxic Activity of New Adamantyl O‐Acylamidoximes and 3‐Aryl‐5‐Adamantane‐1,2,4‐Oxadiazole Derivatives

“…Reaction times were reduced to 25 min ( 4 g ) and 10 min ( 4 d ), affording high yields of 84 and 98%, respectively (entries 4 and 5). No reaction under solvent‐free condition was detected, confirming previously reported DMF‐dependence of such cyclodehydration reaction . When FMW was not used, reactions under similar conditions (Method C, oil bath/110 ° C/DMF) took longer times to achieve comparable yields (entries 6 and 7).…”

Unveiling the Chemo‐ and Regioselectivity of the [3+2] Cycloaddition Reaction between 4‐Chlorobenzonitrile Oxide and β‐Aminocinnamonitrile with a MEDT Perspective**

“…Owing to the diverse applications of oxadiazole derivatives in pharmaceutical chemistry, [1] this class of five-membered heterocycles has been a subject of interest for synthetic organic chemists. [2][3][4][5][6][7][8] Amongst the four isomers (1-4) associated with the oxadiazole skeleton (Scheme 1), the biological activity of 1,2,4-oxadiazole ring 2 was identified in the early 1940s, although the synthesis dates back to 1884 by Tiemann and Kruger. [9] Commercial drugs with the 1,2,4-oxadiazole 2 core were introduced as cough suppressants [10][11][12] and subsequently the anticancer, anti-inflammatory, antiparasitic, antiviral, antibacterial, antidepressant, analgesic and anticonvulsant properties were discovered in the last 40 years (Scheme 2).…”

Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery

“…Another interesting, one-pot synthetic procedure of 3,5-disubstituted-1,2,4-oxadiazoles from the corresponding amidoximes and carboxylic acids employing the -COOH group activation via reaction with Vilsmeier reagent (Scheme 2) was reported by Zarei M. [45]. Good to excellent yields (61-93%), a simple purification protocol, an application of readily available starting materials and one-pot synthesis approach highlighted the benefits of using this procedure.…”