Recent Advances in Metal-Free Quinoline Synthesis

Abstract

Abstract:The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes. Quinolines were first synthesized in 1879, and since then a multitude of synthetic routes have been developed. Many of these methods, such as the Skraup, Doebner-Von Miller, and Friedlander quinoline syntheses, are well-known but suffer from inefficiency, harsh reaction conditions, and toxic reagents. This review focuses on recent transition metal-free processes toward these important heterocycles, including both novel routes and modifications to established methods. For example, variations on the Skraup method include microwave irradiation, ionic liquid media, and novel annulation partners, all of which have shown increased reaction efficiency and improved yield of the heteroring-unsubstituted quinoline products. Similarly, modifications to other synthetic routes have been implemented, with the quinoline products displaying a wide variety of substitution patterns.

Branched C=C and C−N Bond Cleavage on Enaminones toward the Synthesis of 3‐Acyl Quinolines

“…[2] Despite of the history in the research of quinoline chemistry,t he synthesis of quinolines remains as an active area of concurrent organic synthesis. [3] An umber of different synthetic methodologies toward the quinoline synthesis are known. Alongside the classicalS kraup, [4] Combes, [5] and Friedländer [6] reactions, many other alternative methods, such as A 3 coupling-based domino reactions, [7] domino [4+ +2] cycloadditions, [8] CÀHa ctivation initiated domino reactions, [9] domino reactions based on carbonyl or precursor group condensation, [10] and various other types of cyclization reactions, have been developed.…”

Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs

“…But, only by the end of 1800 strategies for synthesis of quinine alkaloids have developed [6] and became an industrial process during the Second World War, when it has strived to produce synthetic AM treatments for the soldiers [3]. This also led to the synthesis of acridine, from which mepacrine (commercialized as Atabrine) was developed becoming another fundamental AM drug [7].…”

Synthesis of Functionalized Quinolines from 4‐(o‐Nitroaryl)‐Substituted 3‐Acyl‐4,5‐Dihydrofurans: Reductive Cyclization and C=C Bond Cleavage

“…Currently, to furnish wide structural and functional diversity of quinoline‐based compounds, classical approaches (such as Skraup, Doebner‐von Miller, Friedländer, Pfitzinger, Conrad‐Limpach, and Combes reactions) are used along with relevant new methods to assemble the quinoline core and introduce desirable substituents into the pre‐existing bicycle . In this context, we report a new synthesis of quinoline‐based structures by intramolecular reduction‐triggered transformations, of 4‐( o ‐nitroaryl)‐3‐acyl‐substituted 4,5‐dihydrofurans.…”

“…methods to assemble the quinoline core and introduce desirable substituents into the pre-existing bicycle. [9][10][11][12][13][14][15][16][17][18][19][20] In this context, we report a new synthesis of quinoline-based structures by intramolecular reduction-triggered transformations [21,22] of 4-(o-nitroaryl)-3-acyl-substituted 4,5-dihydrofurans. The method allows for the synthesis of functionalized quinolones, 1,2,3,4-tetrahydro-and 3,4-dihydroquinolines as well as tricyclic dihydrofuroquinoline derivatives (Scheme 1).…”