Direct Amination of Nitroquinoline Derivatives via Nucleophilic Displacement of Aromatic Hydrogen

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

doi:10.3390/molecules26071857

Direct Amination of Nitroquinoline Derivatives via Nucleophilic Displacement of Aromatic Hydrogen

Molecules. 2021 Mar 25;26(7):1857. doi: 10.3390/molecules26071857.

Authors

Jakub Wantulok¹, Daniel Swoboda¹, Jacek E Nycz¹, Maria Książek², Joachim Kusz², Jan Grzegorz Małecki¹, Vladimír Kubíček³

Affiliations

¹ Faculty of Science and Technology, Institute of Chemistry, University of Silesia in Katowice, ul. Szkolna 9, PL-40007 Katowice, Poland.
² Faculty of Science and Technology, Institute of Physics, Univeristy of Silesia in Katowice, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
³ Faculty of Pharmacy in Hradec Králové, Charles University Prague, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.

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.

Keywords: Meldrum’s acid; Skraup; amination; heterocyclic; nitration; nucleophilic aromatic substitution (SNAr); vicarious nucleophilic substitution of hydrogen.