8-Hydroxy-5-nitroquinoline as a C-nucleophilic reagent in the reaction of C, C-coupling with quinazoline

Tatyana A. Pospelova,Oleg S. Eltsov,Olga S. Koptyaeva,Anton N. Tsmokalyuk,Yuri A. Azev

doi:10.15826/chimtech.2020.7.4.18

Abstract

The first example of the reaction of 5-nitro-8-hydroxyquinoline as a C-nucleophile with quinazoline is described. As a result of the reaction of C, C-coupling, a stable σ-adduct containing the drug nitroxalin on a heterocyclic carrier was obtained. The structure of the resulting adduct was confirmed by 2D 1H-13C HSQC, 1H-13C HMBC, and 1H-15N HMBC spectra.

Highlights

5‐nitro-8‐hydroxyquinoline is an antimicrobial agent from the group of hydroxyquinolines
The data presented in the literature confirm the presence of an electrophilic center on the C6 atom and a nucleophilic center on the C7 atom in the 5‐nitro-8‐hydroxyquinoline molecule
It is obvious that the oxygen-containing substituents (8‐hydroxy and 5‐nitro group) cause a polarization of the electron density in the aromatic nucleus that is higher than that in the heterocyclic part of the nitroxaline molecule

Summary

Introduction

5‐nitro-8‐hydroxyquinoline (nitroxaline) is an antimicrobial agent from the group of hydroxyquinolines. It seems promising to carry out the synthesis of new derivatives of 8‐hydroxyquinolines by means of environmentally friendly C–C coupling reactions, during which the addition of a C-nucleophile to the 8‐hydroxyquinoxaline molecule occurs, followed by the replacement of a hydrogen atom [3]. It was known that 5‐nitro-8‐hydroxyquinoline 1 reacted with formaldehyde in the presence of amines, to form 7‐substituted aminomethyl derivatives of 5‐nitroquinoline-8‐ol 2 [7] (Scheme 1).

Results

Conclusion