Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions.

Irina A Boyarskaya,Aleksander V Vasilyev,Dmitriy N Zakusilo,Andrey I Puzanov,Dmitry S Ryabukhin,Anna S Zalivatskaya,Darya S Mikson

doi:10.3762/bjoc.17.158

Irina A Boyarskaya, Aleksander V Vasilyev + Show 5 more

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https://doi.org/10.3762/bjoc.17.158

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Abstract

Acetylene derivatives of 1,2,4-oxadiazoles, i.e., 5-(2-arylethynyl)-3-aryl-1,2,4-oxadiazoles, have been obtained, for the first time reported, from 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles by their bromination at the carbon–carbon double bond followed by di-dehydrobromination with NaNH2 in liquid NH3. The reaction of the acetylenyl-1,2,4-oxadiazoles with arenes in neat triflic acid TfOH (CF3SO3H) at room temperature for 1 h resulted in the formation of E/Z-5-(2,2-diarylethenyl)-3-aryl-1,2,4-oxadiazoles as products of regioselective hydroarylation of the acetylene bond. The addition of TfOH to the acetylene bond of these oxadiazoles quantitatively resulted in E/Z-vinyl triflates. The reactions of the cationic intermediates have been studied by DFT calculations and the reaction mechanisms are discussed.

Highlights

Epilepsy [10] and Alzheimer disease [11,12,13]
To the best of our knowledge, there is only one example of 1,2,4-oxadiazole conjugated with an acetylene bond, which is 3-phenylethynyl1,2,4-oxadiazole [23]
Based on our previous works on the chemistry of 1,2,4-oxadiazoles in superacids [24,25], we undertook this study on further investigation of the transformations of these heterocyclic compounds in electrophilic media

Summary

Introduction

The synthesis of compounds of the 1,2,4-oxadiazole series is an actual task in organic and medicinal chemistry (see selected reviews on this topic [14,15,16,17,18,19,20,21,22]). There are no data on the preparation of 1,2,4-oxadiazoles containing a conjugated acetylenic substituent in the position 5 of the heterocyclic ring. Based on our previous works on the chemistry of 1,2,4-oxadiazoles in superacids [24,25], we undertook this study on further investigation of the transformations of these heterocyclic compounds in electrophilic media. The main goals of this work were the synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and the study of their reactions with/without arenes under the conditions of superelectrophilic activation by the Brønsted superacid CF3SO3H (TfOH), the strong Lewis acids AlX3 (X = Cl, Br), or the acidic zeolite CBV-720

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