Preparation and Antibacterial Activity of Some New 4-(2-Heterylidenehydrazinyl)-7-chloroquinoline Derivatives

Trong Duc Le,Tien Cong Nguyen,Ngoc Nam Pham

doi:10.1155/2018/4301847

Abstract

N-(4-Substituted phenyl)acetamides, which were prepared from acetic anhydride and p-substituted anilines, were utilized as precursors for reactions to Vilsmeier-Haack reagent to form 6-substituted-2-chloroquinoline-3-carbaldehydes 3a–c. Meanwhile, a similar reagent was applied to 1-[1-(4-substituted phenyl)ethylidene]-2-phenylhydrazines as substrates, which were synthesized from phenylhydrazine hydrochloride and p-substituted acetophenones, and 1,3-diarylpyrazole-4-carbaldehydes 3d–f were observed as a result. Reactions between the aldehydes 3a–f and 7-chloro-4-hydrazinylquinoline 2, obtained from reaction of 4,7-dichloroquinoline 1 and hydrazine hydrate, formed six new hydrazone compounds, namely, 4-{2-[(6-substituted-2-chloroquinolin-3-yl)methylidene]hydrazinyl}-7-chloroquinolines 4a–c and 4-(2-{[3-(4-substituted phenyl)-1-phenyl-1H-pyrazol-4-yl]methylene}hydrazinyl)-7-chloroquinolines 4d–f. The chemical structures of all synthesized compounds were elucidated by the analysis of IR, 1H, 13C-NMR, and HRMS spectral data. Additionally, all of the synthesized hydrazones were evaluated in terms of cytotoxic activity against four strains of bacteria and four strains of fungus at several concentrations of substrates. As a result, three of them, 4a–c, possess the good ability as growth inhibitor of Bacillus subtilis and Aspergillus niger at the concentration of 25 μg/mL and 50 μg/mL, respectively, while compound 4e only shows a cytotoxic activity against Aspergillus niger at the concentration of 25 μg/mL.

Highlights

Quinoline derivatives, which widely occur in nature, especially alkaloids, have become an important skeleton in synthetic chemistry due to their variety of applications in medicinal, bioorganic, and industrial chemistry
The chemical structure of the hydrazones was elucidated by IR, NMR, and HRMS spectral analysis and their biological activities were reported for the first time
The reaction of hydrazine with the heteroaromatic aldehydes a–f formed six new 4-(2-heterylidenehydrazinyl)-7chloroquinoline compounds a–f. Their chemical structures were elucidated by the analysis of IR, NMR, and HRMS spectral data

Summary

Introduction

Quinoline derivatives, which widely occur in nature, especially alkaloids, have become an important skeleton in synthetic chemistry due to their variety of applications in medicinal, bioorganic, and industrial chemistry. Some hydrazone derivatives possessing a quinoline moiety have been well known as having a broad spectrum of biological activities such as antibacterial [1], anticancer [2], antitubercular [3,4,5], antifungal [6], anti-inflammatory [7], antimalarial [8], and antimicrobial [9, 10]. According to Ferreira et al [11], hydrazone derivatives, which were prepared from the reaction of 7-chloro-4-hydrazinylquinoline and heteroaromatic aldehydes, showed a good antimycobacterial activity in comparison with some drugs such as ethambutol and rifampicin. 7-chloro-4-hydrazinylquinoline was prepared from the reaction of 4,7-dichloroquinoline and hydrazine hydrate and was utilized as the key intermediate material for the synthesis of some new hydrazones containing 2-chloroquinoline or pyrazole moiety. The chemical structure of the hydrazones was elucidated by IR, NMR, and HRMS spectral analysis and their biological activities were reported for the first time

Materials and Methods

Result and Discussion

11 N HN 12

Conclusion