Synthesis of novel hybrid quinoxaline containing triazole and acetamide moieties by azide-alkyne click chemistry: Experimental and theoretical characterization

Abstract

Heterocyclic compounds bearing triazole and quinoxaline possess significant pharmacological activities. Herein, a new quinoxaline derivative containing 1,2,3-triazole moiety was synthesis using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" procedure. The solid state crystal structures of 2-azido-N-(4-methoxyphenyl)acetamide (AMA) and N-(4-methoxyphenyl)-2-(4-((3-methyl-2-oxoquinoxalin-1(2H)-yl)methyl)-1H-1,2,3-triazol-1-yl)acetamide (QTA) were determined by X-ray structure analysis. Density Functional Theory (DFT) computations were performed using DFT/B3LYP with 6-311++G(d,p) basis set in the gas phase to get the optimized geometry of both molecules and detailed insights into the molecular and chemical properties that are inaccessible by experimental ways like global reactivity descriptors and Fukui functions. DFT calculations at the same level of theory, with the POP=NBO keyword, were used to evaluate charge delocalization and hyperconjugative interactions through Natural Bond orbital (NBO) analysis. In the title molecule, C21H20N6O3, the quinoxaline moiety is essentially planar while the whole molecule adopts an approximate "U" shape. In the crystal, the molecules form inversion dimers through slightly slipped pi-stacking interactions between quinoxaline units. These form chains extending along the a-axis direction by a combination of additional pi-stacking interactions as well as N-H center dot center dot center dot N and C-O center dot center dot center dot O hydrogen bonds and C-H center dot center dot center dot pi(ring) interactions. The chains are connected by C-H center dot center dot center dot O and CH center dot center dot center dot N hydrogen bonds. In the azide compound an intramolecular C-H center dot center dot center dot O hydrogen bond helps to establish the rotational orientation of the acetamide group. In the crystal, a stepped arrangements of ribbons approximately parallel to (10(-) 1) is formed by a combination of N-H center dot center dot center dot O, C-H center dot center dot center dot O and C-H center dot center dot center dot N hydrogen bonds. Furthermore, to evaluate the chemical reactivity and charge distribution on molecules, molecular electrostatic potential (MEP) maps and atomic charges, computed by NBO theory were determined. Additionally, local reactive properties of AMA and QTA were determined using Fukui functions and dual descriptor calculations. (C) 2021 Elsevier B.V. All rights reserved.