Superacid-promoted synthesis of quinoline derivatives
Introduction
Quinolines are an important class of heterocycles [1]. This ring system is commonly found in natural products and biologically active substances [2]. This includes medicinal agents such as quinine and the anti-malaria drug (1). Quinolines are also common structural elements in material science applications, polymers, and in dyes/pigments. For example, a well-knownpigment is quinolone yellow (2). While a number of synthetic methods have been developed leading to the quinolone ring system [1], [3], there continues to exist the need for new synthetic methods – especially those utilizing inexpensive reagents or catalysts.
Recently, we described a series of reactions in superacid that provided access to aza-polycyclic aromatic compounds [4], [5], [6], [6](a), [6](b). The superacid-promoted chemistry allowed for the synthesis of a wide-variety of ring systems and substituent patterns. For example, the pyridine derivative 3 reacts in triflic acid to provide the benzo[h]isoquinoline 4 in nearly quantitative yield (eq 1) [5]. This chemistry is thought to involve double protonation of substrate 3 to generate the dicationic intermediate 5. Cyclization is then followed by ipso protonation of the phenyl group (6) followed by elimination of benzene and aromatization of the aza-polycyclic aromaticcompound. As an extension of this methodology leading to condensed arenes, we describe herein an efficient synthetic route to quinolone derivatives. The methodology formally derives the quinolone ring system from anilines and cinnamaldehydes.
Section snippets
Results and discussion
It was hypothesized that vinylogous imines should undergo double protonation and the resulting superelectrophilic intermediates should provide the condensed aromatic ring system – in this case the quinoline ring system. The required substrates (7) are prepared readily by reacting anilines with cinnamaldehydes in ethanol with catalytic acetic acid (eq 2) [7]. Initial
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
The support of the NIGMS-NIH (1R15GM126498-01) is gratefully acknowledged. We acknowledge the generous support from the NSF MRI program (award no. CHE: 1726931) for the purchase of the high-resolution mass spectrometer.
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