The Reactivity of Azidonitrobenzofuroxans towards 1,3-Dicarbonyl Compounds: Unexpected Formation of Amino Derivative via the Regitz Diazo Transfer and Tautomerism Study.

Elena Chugunova,Almir Gazizov,Konstantin Usachev,Vasily Babaev,Victor Syakaev,Sergey Kharlamov,Alena Tulesinova,Rakhmetulla Zhapparbergenov,Nurgali Akylbekov,Alexander Burilov,Daut Islamov,Nurbol Appazov

doi:10.3390/ijms22179646

Abstract

Herein, we report on the reaction of nitro-substituted azidobenzofuroxans with 1,3-dicarbonyl compounds in basic media. The known reactions of benzofuroxans and azidofuroxans with 1,3-dicarbonyl compounds in the presence of bases are the 1,3-dipolar cycloaddition and the Beirut reaction. In contrast with this, azidonitrobenzofuroxan reacts with 1,3-carbonyl compounds through Regitz diazo transfer, which is the first example of this type of reaction for furoxan derivatives. This difference is seemingly due to the strong electron-withdrawing effect of the superelectrophilic azidonitrobenzofuroxan, which serves as the azido transfer agent rather than 1,3-dipole in this case.

Highlights

IntroductionDerivatives of benzo[c][1,2,5]oxadiazole 1-oxide (benzofuroxan) have attracted the attention of chemists due to the biological activity exhibited by this class of heterocycle.Benzofuroxans have been proposed as monoamine oxidase inhibitors [1,2] and calcium channel modulators [3,4], and possess vasodilating and cardiotropic [5], antitumor [6,7,8,9], antiparasitic [10,11], anti-tuberculosis [12,13,14], bactericidal [15,16,17], virucidal, sporicidal, and fungicidal activities [18,19]
1,3-carbonyl compounds through the Regitz diazo transfer
This is in sharp contrast compounds through the Regitz diazo transfer

Summary

Introduction

Derivatives of benzo[c][1,2,5]oxadiazole 1-oxide (benzofuroxan) have attracted the attention of chemists due to the biological activity exhibited by this class of heterocycle.Benzofuroxans have been proposed as monoamine oxidase inhibitors [1,2] and calcium channel modulators [3,4], and possess vasodilating and cardiotropic [5], antitumor [6,7,8,9], antiparasitic [10,11], anti-tuberculosis [12,13,14], bactericidal [15,16,17], virucidal, sporicidal, and fungicidal activities [18,19]. Benzofuroxans are capable of entering substitution reactions [20,21], and nucleophilic addition and cycloaddition reactions both as a dienophile and as a diene [22,23,24] They are characterized by the phenomenon of tautomerism (benzo[c][1,2,5]oxadiazole 1-oxide quickly rearranging into benzo[c][1,2,5]oxadiazole 3oxideviathe open dinitroso form) [25], which often complicates the determination of the 4.0/). (benzo[c][1,2,5]oxadiazole 1-oxide quickly rearranging into benzo[c][1,2,5]oxadi oxideviathe open dinitroso form) [25], which often complicates the determinatio structure of asymmetrically substituted benzofuroxans [26] and makes their der tion a challenging task. We lated that the presence of the azide moiety in the benzofuroxan molecule would a structure of asymmetrically substituted benzofuroxans [26] and makes their derivatization installation aeasy challenging task. of various biologically relevant fragments via a “click” reaction

Methods

Discussion

Conclusion