The following introduces the synthesis methods of common quinoline compounds for the convenience of learning and communication
The cyclization of ortho acyl aminoacetophenone occurs in the presence of an alcohol solution of sodium hydroxide, resulting in the formation of hydroxyquinoline. According to the different reaction sites, the generated products are also different (constructing isomers).
2、Combes Quinoline Synthesis Reaction
The reaction of aniline and β - diketone condensation under acid catalysis to obtain quinoline is similar in mechanism to the Conrad Limpach reaction (in which the substrate is β - ketoester and the product is 4-hydroxyquinoline).
The reaction of aniline and β - ketoester condensation to obtain quinolin-4-one under thermal or acid catalysis. This reaction is similar to the Combes quinoline synthesis reaction.
4、Doebner Quinoline Synthesis Reaction
Under heating conditions, aniline, aldehyde, and pyruvic acid undergo a three component condensation reaction to obtain quinoline-4-carboxylic acid.
The Doebner von Miller reaction, also known as the Skraup Doebner von Miller quinoline synthesis reaction, involves the condensation of aromatic amines with α, β - unsaturated carbonyl compounds to form substituted quinolines. This reaction is a variant of the Skraup reaction. The mechanism can also be explained by the Skraup reaction mechanism
6、Friedl ä nder Quinoline Synthesis Reaction
This reaction refers to the reaction between an adjacent amino aromatic aldehyde or ketone and another molecule of a ketone with an alpha methylene group to obtain quinoline. In the reaction, two substrates are first condensed, and the intermediate obtained is subjected to acid or base catalyzed ring dehydration to obtain quinoline.
The Gould Jacobs reaction is a combination of a series of reactions: firstly, aniline 1 is condensed with alkoxymethylene malonate or acylmalonate 2 to obtain phenylmethylene malonate 3; 2、 3 undergoes cyclization reaction to obtain 4-hydroxy-alkanoate quinoline 4; 3、 Hydrolysis yields acid 5; 4、 Decarboxylation yields 4-hydroxyquinoline 6.
8、Knorr Quinoline Synthesis Reaction
The ester group reaction between aniline and β - ketoester generates β - ketoacylaniline intermediate, which is then cyclized under acid catalysis to form 2-hydroxyquinoline.
9、Meth Cohn Quinoline Synthesis Reaction
In 1978, the Meth Cohn research group reported the reaction of acetyl aniline with Vilsmeier Haack reagent to obtain 2-chloro-3-quinolone formaldehyde (68% yield). The reaction between acylarylamine and Vilsmeier reagent under heating conditions to obtain 2-chloro-3-substituted quinoline is called the Meth-Cohn quinoline synthesis reaction
10、Niementowski Quinoline Synthesis Reaction
The reaction of ortho aminobenzoic acid and aldehyde ketone condensation to obtain 4-hydroxyquinoline derivatives.
The reaction of indigo compounds with aldehydes and ketones under alkaline (KOH) conditions yields quinoline-4-carboxylic acid
The Povarov reaction is an anti electron flow nitrogen doped DA reaction (iEDDA), in which N-arylimine is used as the diene and electron rich alkene is used as the dienophile for [4+2] cycloaddition to obtain tetrahydroquinoline products or substituted quinoline products
The reaction of aniline, glycerol, sulfuric acid, and oxidant (such as PhNO2) to prepare quinoline.
14、Ciamician Dennstedt rearrangement
Pyrrole undergoes rearrangement with haloform (CHX 3 where X=Cl, Br, I) under strong alkaline conditions to form 3-halogenated pyridine. This reaction is caused by G L. Ciamician was first discovered in 1881, and later M Dennstedt used sodium methoxide to catalyze the reaction of pyrrole and diiodomethane to prepare pyridine, making this method more widely applicable. Later, based on this research, the method of using indole and quinoline was also discovered. Therefore, such reactions are collectively referred to as Ciamician Dennstedt rearrangement reactions.
14、 Other
The adjacent amino halogenated aromatic hydrocarbon first undergoes Heck reaction with acrylic ester (or Suzuki reaction with 3-borate ester acrylic ester) to obtain 3- (2-aminophenyl) acrylic ester, and then undergoes intramolecular aminoester exchange cyclization to obtain quinolone. Quinolone can be further derivatized by chlorination with phosphorus oxychloride to obtain 2-chloroquinoline.
The methyl group of ortho nitrotoluene has strong hydrogen acidity【Batcho Leimgruber indole synthesis reaction】，Ester condensation reactions can occur to extend the carbon chain and achieve ring closure. O-nitrotoluene and diethyl oxalate undergo ester condensation reaction, followed by reduction cyclization to obtain 3-hydroxy-3,4-dihydroquinolin-2 (1H) - one, which can be refluxed directly in phosphorus oxychloride while achieving aromatization and chlorination to obtain 2-chloroquinoline.
[XMOL News] Rapid construction of quinoline through hydrogenation amination tandem cyclization reaction of alkynes catalyzed by nickel hydrogen
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Associate Professor Huang Huawen from Xiangtan University: Copper catalyzed [3+3] Heterocyclization of aryl ketoximes and o-fluorobenzaldehyde to Construct Quinoline and Acridine Derivatives
[Organic] Synthesis of Quinoline Spirene via Organic Catalytic Povarov Reaction Series Oxidative Aromatization Enantioselectivity
