Quinoline

Occurrence and isolation

Quinoline was first extracted from coal tar in 1834 by German chemist Friedlieb Ferdinand Runge; Coal tar remains the principal source of commercial quinoline. Runge's and Gephardt's compounds seemed to be distinct isomers because they reacted differently. However, the German chemist August Hoffmann eventually recognized that the differences in behaviors was due to the presence of contaminants and that the two compounds were actually identical. The only report of quinoline as a natural product is from the Peruvian stick insect Oreophoetes peruana. They have a pair of thoracic glands from which they discharge a malodorous fluid containing quinoline when disturbed.

Like other nitrogen heterocyclic compounds, such as pyridine derivatives, quinoline is often reported as an environmental contaminant associated with facilities processing oil shale or coal, and has also been found at legacy wood treatment sites. Owing to its relatively high solubility in water quinoline has significant potential for mobility in the environment, which may promote water contamination. Quinoline is readily degradable by certain microorganisms, such as Rhodococcus species Strain Q1, which was isolated from soil and paper mill sludge.

Quinolines are present in small amounts in crude oil within the virgin diesel fraction. It can be removed by the process called hydrodenitrification.

Synthesis

Quinolines are often synthesized from simple anilines using a number of named reactions. ::[[File:Quinoline from aniline.png|400px|class=skin-invert-image]] Going clockwise from top these are:

• Combes quinoline synthesis using anilines and β-diketones.
• Conrad-Limpach synthesis using anilines and β-ketoesters.
• Doebner reaction using anilines with an aldehyde and pyruvic acid to form quinoline-4-carboxylic acids
• Doebner-Miller reaction using anilines and α,β-unsaturated carbonyl compounds.
• Gould-Jacobs reaction starting from an aniline and ethyl ethoxymethylenemalonate
• Skraup synthesis using ferrous sulfate, glycerol, aniline, nitrobenzene, and sulfuric acid.

A number of other processes exist, which require specifically substituted anilines or related compounds:

• Camps quinoline synthesis using an o-acylaminoacetophenone and hydroxide
• Friedländer synthesis using 2-aminobenzaldehyde and acetaldehyde
• Knorr quinoline synthesis, using a β-ketoanilide and sulfuric acid
• Niementowski quinoline synthesis, using anthranilic acid and ketones
• Pfitzinger reaction using an isatin with base and a carbonyl compound to yield substituted quinoline-4-carboxylic acids
• Povarov reaction using an aniline, a benzaldehyde and an activated alkene

Quinolines are reduced to tetrahydroquinolines enantioselectively using several catalyst systems.

Applications

Quinolines are used in the manufacture of dyes and the preparation of hydroxyquinoline sulfate and niacin. It is also used as a solvent for resins and terpenes.

Prior to the development of aspirin, quinoline was occasionally used for pain, but had a very bad taste and smell along with serious side effects.

Quinoline is mainly used as in the production of other specialty chemicals. Approximately 4 tonnes were produced annually according to a report published in 2005.

The reduction of quinoline with sodium borohydride in the presence of acetic acid is known to produce Kairoline A. (Cf. Kairine)

Several anti-malarial drugs contain quinoline substituents. These include quinine, chloroquine, amodiaquine, and primaquine.

Quinoline is used as a solvent and reagent in organic synthesis.

Quinolinium compounds (e.g. salts) can also be used as corrosion inhibitors and intensifiers.

References

References

1. (2014). "Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book)". [[Royal Society of Chemistry.
2. Brown, H.C., et al., in Baude, E.A. and Nachod, F.C., ''Determination of Organic Structures by Physical Methods'', Academic Press, New York, 1955.
3. "QUINOLINE (BENZOPYRIDINE)". Chemicalland21.com.
4. {{cite EB1911
5. (May 2018). "Biologically active quinoline and quinazoline alkaloids part I.". Medicinal Research Reviews.
6. (September 2018). "Biologically active quinoline and quinazoline alkaloids part II". Medicinal Research Reviews.
7. he called quinoline ''leukol'' ("white oil" in Greek).F. F. Runge (1834) [https://books.google.com/books?id=wCUAAAAAMAAJ&pg=PA65 "Ueber einige Produkte der Steinkohlendestillation"] (On some products of coal distillation), ''Annalen der Physik und Chemie'', '''31''' (5) : 65–78; see especially p. 68: "3. Leukol oder Weissöl" (3. White oil [in Greek] or white oil [in German]). From p. 68: ''"Diese dritte Basis habe ich Leukol oder Weissöl genannt, weil sie keine farbigen Reactionen zeigt."'' (This third base I've named ''leukol'' or white oil because it shows no color reactions.)
8. In 1842, French chemist [[Charles Frédéric Gerhardt
9. Initially, Hoffmann thought that Runge's ''Leukol'' and Gerhardt's ''Chinolein'' were distinct. (See: Hoffmann, August Wilhelm (1843) [https://babel.hathitrust.org/cgi/pt?id=hvd.hx3bgr;view=1up;seq=51 "Chemische Untersuchungen der organischen Basen im Steinkohlen-Theeröl"] (Chemical investigations of organic bases in coal tar oil), ''Annalen der Chemie und Pharmacie'', '''47''' : 37-87; see especially pp. 76-78.) However, after further purification of his ''Leukol'' sample, Hoffmann determined that the two were indeed identical. (See: (Editor) (1845) [https://babel.hathitrust.org/cgi/pt?id=uiug.30112025846970;view=1up;seq=442 "Vorläufige Notiz über die Identität des Leukols und Chinolins"] (Preliminary notice of the identity of leukol and quinoline), ''Annalen der Chemie und Pharmacie'', '''53''' : 427-428.)
10. Eisner, T; Morgan, R.C.; Attygalle A.B., Smedley, S.R.; Herath, K.B., Meinwald, J. (1997) “Defensive Production of quinoline by a phasmid insect (Oreophoetes peruana) J. Exp. Biol. 200, 2493–2500.
11. (1996). "Isolation, characterization, and substrate utilization of a quinoline-degrading bacterium". International Biodeterioration & Biodegradation.
12. Xu, L.; Lam, K. H.; Ji, J.; Wu, J.; Fan, Q.-H.; Lo, W.-H.; Chan, A. S. C. ''Chem. Commun.'' '''2005''', 1390.
13. Reetz, M. T.; Li, X. ''Chem. Commun.'' '''2006''', 2159.
14. (2005-06-30). "Pain relief: from coal tar to paracetamol". [[Royal Society of Chemistry]].
15. (1975). "Reactions of Sodium Borohydride in Acidic Media; III. Reduction and Alkylation of Quinoline and Isoquinoline with Carboxylic Acids". Synthesis.
16. (2001). "Encyclopedia of Reagents for Organic Synthesis".