Elsevier

Tetrahedron

Volume 63, Issue 32, 6 August 2007, Pages 7654-7658
Tetrahedron

Synthesis and characterization of quinoline derivatives via the Friedländer reaction

https://doi.org/10.1016/j.tet.2007.05.037Get rights and content

Abstract

A rapid and efficient method for the synthesis of various poly-substituted quinolines has been developed via the Friedländer condensation of 2-aminoarylaldehyde with a carbonyl compound containing a reactive α-methylene group in the presence of sodium ethoxide (10 mol %). The new tetrahydroacridine derivatives and 11H-indeno[1,2-b]quinolines were synthesized in high yield with sodium ethoxide as a catalyst via the Friedländer reaction. The conditions of reaction were discussed and the possible reaction mechanism was proposed.

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A rapid and efficient method for the synthesis of various poly-substituted quinolines has been developed via the Friedländer condensation of 2-aminoarylaldehyde with a carbonyl compound containing a reactive α-methylene group in the presence of sodium ethoxide (10 mol %). The new tetrahydroacridine derivatives and 11H-indeno[1,2-b]quinolines were synthesized in high yield with sodium ethoxide as a catalyst via the Friedländer reaction. The conditions of reaction were discussed and the possible reaction mechanism was proposed.

Introduction

The quinoline nucleus occurs in several natural compounds (cincona alkaloids) and pharmacologically active substances displaying a broad range of biological activity.1, 1(a), 1(b), 1(c) The biological activity of quinoline compounds has been found to possess antiasthmatic, antibacterial, anti-inflammatory, and antihypertensive properties. In addition to the medicinal applications, quinolines have been employed in the study of bioorganic and bioorganometallic processes. Quinolines are also known for their formation of conjugated molecules and polymers that combine enhanced electronic, optoelectronic, or nonlinear optical properties with excellent mechanical properties.2 The Friedländer reaction is a well-known method for preparing quinolines and polypyridyl bridging ligands,3 it is still considered as one of the most useful methods for preparing quinolines and related bicyclic azaaromatic compounds. In its original form, the Friedländer reaction is the reaction between an aromatic ortho-aminoaldehyde and an aldehyde or ketone bearing α-methylene functionality. Since Friedländer's initial discovery, the reaction has been extended to a wide range of substrates, including aromatic ortho-aminoketones and nitrogen-containing heterocycles.4

In recent years, the chemists were interested in studies of the reaction with low waste and reusable reaction media for enhanced selectivity and minimized energy.5 A number of other methods have been reported for the synthesis of quinolines involving a variety of metal catalysts and Lewis acids.6, 6(a), 6(b), 6(c), 6(d) Brønsted acid catalysts, such as hydrochloric acid, perchloric acid, sulfuric acid, p-toluene sulfonic acid, sulfamic acid, phosphoric acid, and trifluoro acetic acid were widely used for the Friedländer reaction.7, 7(a), 7(b), 7(c) However, many of these procedures are not fully satisfactory with regard to operational simplicity, cost of the reagent, drastic reaction conditions, and relatively low yield. Therefore, a simple, general, and efficient procedure is still in demand for the preparation of these important heterocyclic compounds and continues to find a better and improved methodology. In this paper, we have demonstrated a very efficient and environmentally benign strategy for the synthesis of new tetrahydroacridine derivatives and 11H-indeno[1,2-b]quinolines with good to excellent yields.

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Results and discussion

Friedländer reaction in the presence of a catalytic amount of sodium ethoxide for about 2–3 h resulted in a complete consumption of substrates. Our approach to the synthesis of 3ai and 6ai were based on the Friedländer condensation strategy. The intermediates 1ai and 4ai were obtained by nitration of the arylaldehyde followed by reduction of ortho-nitroarylaldehyde. The intermediates used in the Friedländer reaction reacted with 2ai and 5ai, separately, to form quinoline derivatives. The

General

All reagents and solvents were of reagent grade. Melting points were determined on a microscopic melting point apparatus (Kofler) and were uncorrected. 1H NMR (400 MHz) and 19F NMR (282 MHz) were recorded in CDCl3 or DMSO-d6 solutions with TMS as the respective internal standards. Mass spectra were obtained with Thermofinnigan MAT95XL spectrometer system. Relevant data were tabulated as m/z. The IR spectra were recorded on a Perkin–Elmer Model 1730 FTIR spectrometer using KBr film. The 1H NMR

Acknowledgements

We would like to thank the Natural Science Foundation of Guangdong Province for the financial support (No. 04010404).

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