The synthesis of quinoline derivatives from primary aromatic amines, glycerol, and an oxidizing agent in concentrated sulfuric acid is generally known as the skraup reaction. Recent advances in metalfree quinoline synthesis mdpi. Pyrrolo1,2a quinoline, 2nitrophenylacetic acid, 2aminophenylacetic acid, pdc catalysed hydrogenolysis, ammonium formate. Potential exposure to quinoline may occur from the inhalation of cigarette smoke.
Reaction mechanism of the skraup quinoline synthesis. Quinolines have antiseptic, antipyretic, and antiperiodic properties and are used as antimalarials and for preparing other antimalarial drugs. The product is a quinoline containing only those substituents that were originally present in the aromatic amine. Synthesis of benzoh quinoline by the skraup procedure is also carried out by heating 1naphthylamine with glycerol in the presence of sulfomix, 396 ferrous sulfate, and boric acid. Quinoline can be prepared by heating a mixture of aniline, glycerol, and sulfuric acid 1 alone or with an oxidizing agent like nitrobenzene, 2 arsenic acid, 3 ferric oxide, 4 and vanadic acid. Quinoline substructure structure of quinine reported by german chemist paul rabe in 1907. It has been reported that initial skraup protocol usually gives a very low yield of quinolines. Friedlander prepared quinoline in 1882 by the condensation of o aminobenzaldehyde with acetaldehyde in the presence of sodium hydroxide. Skraups synthesis is a chemical reaction used to synthesize quinolines by the condensation of glycerine. Shaikh abstract for the synthesis of substituted i.
The skraup synthesis is a chemical reaction used to synthesize quinolines. Several alkaloid quinoline compounds found in plants are important medicines. Activity relationship of 4substituted 22acetyloxyethyl8morpholine 4sulfonylpyrrolo3,4cquinoline 1,3diones as potent caspase3 inhibitors dmitri v. On the basis of these studies, a mechanistic pathway for the skraup quinoline synthesis is proposed that involves a fragmentation. Starting from 2nitrophenylacetic acid, the synthesis of some pyrrolo1,2a quinoline derivaives has been reduced to an experimentally simple threestep operation. Organometallic derivatives of quinoline and isoquinoline. This reaction was first studied in 1880 by zdenko hans skraup 18501910, a czech scientist born in prague city of czech republic. The synthesis of five quinolines 8octyloxy44octyloxyphenylquinoline and 6alkoxy.
A highly efficient synthesis of 2chloro 3formyl8methyl quinoline. Other limitations include the use of highly concentrated glycerol that contains less than. Coal tar remains the main source of commercial quinoline. Many of these methods, such as the skraup, doebnervon miller, and friedlander quinoline syntheses, are wellknown but suffer from. New quinoline 2one derivatives were synthesized by reaction of 4,7dimethyl coumarin i with nitric acid in the presence of concentrated sulfuric acid to afford 4,7dimethyl6nitrocoumarin ii and 4,7dimethyl8nitrocoumarin iii. The synthesis of quinoline derivatives has been prevalent in biomedical studies due to the efficiency of the synthetic methods as well as the relative lowcost production of these compounds, which can also be produced in large scales. The mechanism of the formation of substituted quinolines from anilines and. Quinoline is a heterocyclic aromatic organic compound with the chemical formula c 9 h 7 n. Request pdf skraup quinoline synthesis quinoline from aniline, glycerol, sulfuric acid and oxidizing agent e. Files are available under licenses specified on their description page. Synthesis and characterization of some quinoline azosulphonanides clubbed molecule. Fiorito j1, saeed f, zhang h, staniszewski a, feng y, francis yi, rao s, thakkar dm, deng sx, landry dw, arancio o.
Aged samples, if exposed to light,become yellow and later brown. Quinoline is only slightly soluble in cold water but dissolvesreadily in hot water and most organic solvents. Because of the similarity of these to the reagents in the friedlander quinolone synthesis, a benzaldehyde with an aldehyde or ketone, the niementowski quinoline synthesis mechanism is minimally different from that of the friedlander synthesis. An expeditious synthesis some pyrrolo1,2aquinoline derivatives. Abstract new quinolines substituted with various heterocycles and chalcone moieties were synthesized and evaluated as antitumor agents. Brought to you by the organic reactions wiki, the online collection of organic reactions. There are multiple ways to synthesize quinoline, one of which is the combes quinoline synthesis. Nov 03, 2012 this reaction was first studied in 1880 by zdenko hans skraup 18501910, a czech scientist born in prague city of czech republic. Toluenesulfonic acid, being an efficient, nonhazardous, and fast accessible organocatalyst, was used for the preparation of.
Itis a colorless hygroscopic liquid with a strong odor. He apprenticed under lieben at the university of vienna. The classic skraup synthesis of quinoline uses hot aniline, nitrobenzene and glycerol in the presence of catalytic sulfuric acid and produces low yields of product fig. A simple, efficient and convenient coppercatalyzed method allows the synthesis of quinoline 2carboxylate derivatives through sequential intermolecular addition of alkynes onto imines and subsequent intramolecular ring closure by arylation at room temperature. Synthesis and biological activity investigation of some. Skraup synthesis of quinolines organic reactions wiki. Zdenko hans skraup 18501910 was born in prague, czechoslovakia. Therefore, extensive modifications have been made based on the initial. In the synthesis of pyridines it proved advantageous to make a dihydropyridine and oxidize it to a pyridine afterwards. Isoquinoline is a heterocyclic aromatic organic compound.
Synthesis of benzo f quinoline and its derivatives. The described syntheses highlighted in this manuscript consist in the first skraup synthesis presented in the literature by. Apr 15, 2020 quinoline, any of a class of organic compounds of the aromatic heterocyclic series characterized by a doublering structure composed of a benzene and a pyridine ring fused at two adjacent carbon atoms. In a later investigation bergstrom and mcallister ob tained 2phenylqulnollne in a yield of qq% by autoclavlng an ethereal solution of quinoline and phenylmagneslum bromide at 150160 for three hours. Quinoline derivatives are prevalent in a variety of pharmacologically active synthetic and natural compounds. Nov 09, 2012 quinoline is a heterocyclic aromatic organic compound with the chemical formula c9h7n. Synthesis of quinoline tertiary amines 5 ap from 4ad using hunigs base at r.
It is named after the czech chemist zdenko hans skraup 18501910. The journal of organic chemistry 2006, 71 17, 65926595. Shortly after the isolation of quinoline from coal tar, it was also recognised as a. Quinoline breaks down quickly in the atmosphere and water. Reaction of 1naphthylamine with ethylpropiolate in toluene as solvent and trifluoroacetic acid as acid and microwave irradiation at 150c yielded. In a broader sense, the term isoquinoline is used to make reference to isoquinoline derivatives. Acute shortterm inhalation exposure to quinoline vapors irritates the eyes, nose. Quinolines heterocyclic building blocks sigmaaldrich. Quinolines substituted in the hetero ring may be obtained by a modified skraup synthesis in which a substituted acrolein or a vinyl ketone is used in place of glycerol. Quinoline not only has a wide range of biological and pharmacological activities but there are several established protocols for the synthesis of this ring. Find, read and cite all the research you need on researchgate. All structured data from the file and property namespaces is available under the creative commons cc0 license.
Aged samples, especially if exposed to light, become yellow and later brown. Isoquinoline and quinoline are benzopyridines, which are composed of a benzene ring fused to a pyridine ring. Thus, this lownucleophilic strong base table 4 forms a salt with the released hydrogen chloride allowing the reaction to proceed under mild reaction conditions. Ultrasound promoted synthesis of quinolines 16 using basic ionic liquids bil in. In the archetypal skraup reaction, aniline is heated with sulfuric acid, glycerol, and an oxidizing agent such as nitrobenzene to yield quinoline. Quinoline 91225 hazard summary quinoline is used mainly as an intermediate in the manufacture of other products. The reaction sequence employed for synthesis of the key scaffold, 4hydrazinyl2,8bistrifluoromethyl quinoline 3 is shown in scheme 1. Quinoline ring has been found to possess antimalarial, antibacterial, antifungal, anthelmintic, cardiotonic, anticonvulsant, antiinflammatory, and analgesic activity. Skraup synthesis article about skraup synthesis by the free.
Evidence on the carcinogenicity of quinoline and its strong salts. Skraup reaction major reference works wiley online. Mar 10, 2020 zbigniew wrobel, andrej kwast, mieczyslaw makosza, synthesis 1993, p. Synthesis of derivatives of 2 phenyl quinoline 4 carboxylic acid. Synthesis and reactions of a new quinone quinoline 7. Friedlander reaction, quinoline derivatives, heteropoly compound, supported catalysts, solventfree condition. We report here the continuous reaction of solketal with anilines over a solid acid niobium phosphate nbp, for the continuous generation of quinolines in the wellestablished skraup reaction. Mandewale1, bapu thorat1, udaysinha patil1, bhima kale and ramesh yamgar2 1department of chemistry, government of maharashtra, ismail yusuf college of arts, science and commerce, jogeshwari east mumbai400 060, india. Design, synthesis, and docking study of new quinoline derivatives. The same idea works well in probably the most famous quinoline synthesis, the skraup reaction. In the reaction of doubly labeled c2,4 mesityl oxide, a 100% scrambling of the label in the quinoline product was observed, whereas only a small 5.
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