Substitutions of fluorine atoms and phenoxy groups in the synthesis of quinoxaline 1,4-di-N-oxide derivatives

E Vicente,S Pérez-Silanes,A Burguete,R Villar,A Monge,I Aldana,B Solano

doi:10.3390/ecsoc-11-01332

Abstract

The unexpected substitution of fluorine atoms and phenoxy groups linked to quinoxaline or benzofuroxan rings is described. The synthesis of 2-benzyl and 2-phenoxy3-methylquinoxaline 1,4-di-N-oxide derivatives was based on the classical Beirut reaction. The experimental conditions (reaction solvent and catalyst) were explored with the aim of obtaining the target compounds.

Highlights

Quinoxaline and quinoxaline-1,4-di-N-oxide are heterocycles that are frequently used in the synthesis of biologically active compounds [1,2,3,4]
The synthesis of each of these compounds was based on the classical Beirut reaction and, in this case, methanol and gaseous ammonia were chosen as reaction solvent and catalyst, respectively
It is well known that the phenoxy scaffold is a good leaving group and that the ammonia gas is a potent base; the curious part is that first the quinoxaline is formed and later, the substitution occurs (Scheme 2)

Summary

Introduction

Quinoxaline and quinoxaline-1,4-di-N-oxide are heterocycles that are frequently used in the synthesis of biologically active compounds [1,2,3,4]. With regards to Carta’s paper [19], this series, together with a series of 2-phenoxy-3-methylquinoxaline 1,4-di-N-oxide derivatives, could complete the bioisosterism replacements based on Grimm’s Hydride Displacement Law (Scheme 1). This law states that the addition of a hydrogen atom with a pair of electrons (i.e. hydride) to an atom belonging to groups 4A, 5A, 6A, 7A on the Periodic Table, produces an isoelectronic pseudoatom, showing the same physical properties as those present in the column immediately behind the initial atom on the Periodic Table of the Elements [5]. The aim of this work was to obtain 2-benzyl- and 2-phenoxy-3methylquinoxaline 1,4-di-N-oxide derivatives as potential antitubercular drug candidates

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Conclusion