Direct Amination of Nitroquinoline Derivatives via Nucleophilic Displacement of Aromatic Hydrogen.

Jakub Wantulok,Joachim Kusz,Vladimír Kubíček,Maria Książek,Jacek E Nycz,Jan Grzegorz Małecki,Daniel Swoboda

doi:10.3390/molecules26071857

Abstract

The vicarious nucleophilic substitution of hydrogen (VNS) reaction in electron-deficient nitroquinolines was studied. Properties of all new products have been characterized by several techniques: MS, HRMS, FTIR, GC-MS, electronic absorption spectroscopy, and multinuclear NMR. The structures of 4-chloro-8-nitroquinoline, 8-(tert-butyl)-2-methyl-5-nitroquinoline, 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one were determined by single-crystal X-ray diffraction measurements. The 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one illustrate the nitro/nitroso conversion within VNS reaction. Additionally, 9-(8-isopropyl-2-((8-isopropyl-2-methyl-5-nitroquinolin-6-yl)methyl)-5-nitrosoquinolin-6-yl)-9H-carbazole is presented as a double VNS product. It is postulated that the potassium counterion interacts with the oxygen on the nitro group, which could influence nucleophile attack in that way.

Highlights

Received: 16 February 2021Accepted: 23 March 2021Published: 25 March 2021Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Licensee MDPI, Basel, Switzerland.The worldwide annual production of quinoline derivatives is more than 2000 tonnes, of which 8-hydroxyquinoline makes up the main part [1]
We present the amination procedures of selected nitroquinoline derivatives
We chose the direct nitration of selected 8-(alkyl)-2-methylquinolines, which was a one-step method to introduce carbon-nitrogen bond and requires higher electron density in benzene rings as described earlier [4]

Summary

Introduction

Received: 16 February 2021Accepted: 23 March 2021Published: 25 March 2021Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Licensee MDPI, Basel, Switzerland.The worldwide annual production of quinoline derivatives is more than 2000 tonnes, of which 8-hydroxyquinoline makes up the main part [1]. The amino group is the essential building block of many molecules found in nature, e.g., peptides and proteins. Introducing this moiety into molecular structures is a crucial process, no matter the scale of the reaction and the purpose of the application. To explore the structure-function relationship of biologically active quinoline compounds, such as their coordination metal ability, the study of amination of nitroquinoline derivatives was carried out in our laboratory. The amination reactions of 4,7-dichloro-1,10-phenanthrolines using bulky 9H-carbazole, 10H-phenothiazine, and pyrrolidine nucleophiles were reported by our group [2]. Two fully characterized products of a similar chemical transformation, the oxidative nucleophilic substitution of hydrogen (ONSH), were presented (Figure 1) [2]

Methods

Results

Conclusion