1. Quinoline is a heterocyclic aromatic organic compound with the chemical formula C9H7N. It is colorless and hygroscopic, becoming yellow and brown over time when exposed to light. 2. Quinoline itself has few applications but many derivatives are useful, including quinine which is an important anti-malarial drug. Over 200 biologically active quinoline alkaloids have been identified. 3. The document discusses the structure, properties, synthesis methods like Skraup, Doebner-Miller, and Conrad-Limpach, reactions including electrophilic substitution, oxidation, and reduction, and applications of quinoline and its derivatives in dyes

1. FUSED HETEROCYCLES
WITH ONE HETEROATOMS
QUINOLINE
BY – VISHAL SINGH SOLANKI
A.P. AT IDEAL INSTITUTE, POSHERI, WADA, PALGHAR, M.H.
EMAIL – vishalsolanki393@gmail.com

2. QUINOLINE

3. Quinoline is a heterocyclic aromatic organic compound with the chemical formula C9H7N.
It is a colourless hygroscopic liquid with a strong odour.
Aged samples, especially if exposed to light, become yellow and later brown.
Quinoline is only slightly soluble in cold water but dissolves readily in hot water and most
organic solvents.
Quinoline itself has few applications, but many of its derivatives are useful in diverse
applications.
A prominent example is quinine, an alkaloid found in plants.
Over 200 biologically active quinoline and quinazoline alkaloids are identified.
4-Hydroxy-2-alkylquinolines (HAQs) are involved in antibiotic resistance.
INTRODUCTION

4. Quinoline, any of a class of organic compounds of the aromatic heterocyclic
series characterized by a double-ring structure composed of a benzene and
a pyridine ring fused at two adjacent carbon atoms.
The benzene ring contains six carbon atoms, while the pyridine ring contains
five carbon atoms and a nitrogen atom.
The simplest member of the quinoline family is quinoline itself,
a compound with molecular structure C9H7N.
CONTI…

5. STRUCTURE

6. All ring atoms in Quinoline are SP2 hybridize.
The nitrogen lone pair electrons reside in an SP2 orbital and not involved in the
formation of the delocalized π molecular orbital.
It shows aromatic properties because its π orbital contains ten electrons & satisfied the
Huckel’s rule (n = 2 is 4n+2).
RESONANCE

7. PHYSIAL PROPERTIES
Chemical formula C9H7N
Molar mass 129.16 g/mol
Appearance Colorless oily liquid
Density 1.093 g/mL
Melting point −15 °C (5 °F; 258 K)
Boiling point 237 °C (459 °F; 510 K) , 760 mm Hg; 108–110 °C
(226–230 °F), 11 mm Hg
Solubility in water Slightly soluble
Solubility Soluble in alcohol, ether, and carbon disulfide
Other IUPAC name 1-Benzopyridine, Benzo[b]pyridine

8. 1. Combes quinoline synthesis using anilines and β-diketones.
2. Conrad-Limpach synthesis using anilines and β-keto esters.
3. Doebner reaction using anilines with an aldehyde and pyruvic acid to form quinoline-
4-carboxylic acids
4. Doebner-Miller reaction using anilines and α,β-unsaturated carbonyl compounds.
5. Gould-Jacobs reaction starting from an aniline and ethyl ethoxy methylene malonate
6. Skraup synthesis using ferrous sulfate, glycerol, aniline, nitrobenzene, and sulfuric
acid.
7. Friedländer synthesis using 2-aminobenzaldehyde and acetaldehyde
SYNTHESIS

9. CONTI…

10. In the archetypal Skraup reaction, aniline is heated with sulfuric acid, glycerol,
and an oxidizing agent such as nitrobenzene to yield quinoline.
SKRAUP SYNTHESIS

11. MECHANISM

12. The Doebner–Miller reaction is the organic reaction of an aniline with α,β-unsaturated
carbonyl compounds to form quinolines.
The reaction is catalyzed by Lewis acids such as tin tetrachloride and scandium(III)
triflate and Brønsted acids such as p-toluenesulfonic acid, perchloric acid, amberlite and iodine.
DOEBNER–MILLER SYNTHESIS

13. CONRAD–LIMPACH SYNTHESIS
The Conrad–Limpach synthesis is the condensation of anilines (1) with β-ketoesters (2) to
form 4-hydroxyquinolines (4) via a Schiff base (3). The overall reaction type is a combination of
both an addition reaction as well as a rearrangement reaction.

14. MECHANISM

15. The Friedländer synthesis is a chemical reaction of 2-amino
benzaldehydes with ketones to form quinoline derivatives.
This reaction has been catalysed by trifluoroacetic acid, toluene sulfonic
acid, iodine, and Lewis acids.
FRIEDLÄNDER SYNTHESIS

16. In the first mechanism 2-amino substituted carbonyl compound 1 and carbonyl
compound 2 react in a rate-limiting step to aldol adduct 3.
This intermediate loses water in an elimination reaction to unsaturated carbonyl
compound 4 and then loses water again in imine formation to quinoline 7.
In the second mechanism the first step is Schiff base formation to 5 followed by
Aldol reaction to 6 and elimination to 7.
MECHANISM

17. MECHANISM

18. 1. ELCTROPHILIC SUBSTITUTION REACTION
2. NUCLEOPHILIC SUBSTITUTION REACTION
3. OXIDATION
4. REDUCTION
5. HETEROATOM REACTION
CHEMICAL REACTION

19. Electrophilic substitution reactions occur on the ring C-atoms, mainly on those of the more activated benzene
moiety.
Electrophilic substitution reactions occur in positions 5 and 8 of quinoline.
Nucleophilic substitution proceeds faster in quinoline than in pyridine.
Nucleophilic substitution of quinoline occurs in the electron deficient pyridine ring, as a rule in the position 2
or 4.
Treatment of quinoline with nitrating mixture results in 5and 8-nitroquinolines.
Sulphonation of quinoline produces different products depending on the reaction temperature.
At 220°C quinoline8sulphonic acid is formed predominantly; At 300°C, quinoline6sulphonic acid is the sole
product.
When heating to 300°C quinoline8sulphonic acid is converted into quinoline6sulphonic, which is the
thermodynamically favoured Sulphonation product.
ELECTROPHILIC AND NUCLEOPHILIC SUBSTITUTION
REACTIONS

20. The pyridine ring is hydrogenated prior to the benzene ring of quinoline.
The product of reduction depends much upon the reaction conditions.
The alkaline permanganate solution causes oxidative cleavage of the benzene ring in
quinoline to give quinolinic acid (pyridine 2,3-dicarboxylic acid). The reaction of
quinoline with per-oxy carboxylic acids leads to its N-oxide.
Heteroatom reactions: The nitrogen in Quinoline, which undergoes protonation,
alkylation, acylation, etc. Quinoline is a weaker base than pyridine.
OXIDATION AND REDUCTION REACTIONS.

21. CONTI…

22. APPLICATION
1. Quinoline is used in the manufacture of dyes, the preparation of hydroxyquinoline sulphate and niacin.
2. It is also used as a solvent for resins and terpenes.
3. Quinoline is mainly used as in the production of other specialty chemicals.
4. Its principal use is as a precursor to 8-hydroxyquinoline, which is a versatile chelating agent and
precursor to pesticides.
5. Its 2- and 4-methyl derivatives are precursors to cyanine dyes. Oxidation of quinoline affords quinolinic
acid (pyridine-2,3-dicarboxylic acid), a precursor to the herbicide sold under the name "Assert".
6. The reduction of quinoline with sodium borohydride in the presence of acetic acid is known to
produce Kairoline A.
7. Quinoline has several anti-malarial derivatives, including quinine, chloroquine, amodiaquine,
and primaquine.
8. Quinolines are reduced to tetrahydroquinolines enantio-selectively using several catalyst systems.

23. ANY QUESTION ?

24. 1. https://www.researchgate.net/publication/325080072_UNIT_-V_Heterocyclic_Chemistry_Quinoline_Isoquinoline_and_Indole
2. https://en.wikipedia.org/wiki/Quinoline
3. Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The
Royal Society of Chemistry. 2014. pp. 4, 211. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4. The name
‘quinoline’is a retained name that is preferred to the alternative systematic fusion names ‘1-benzopyridine’ or
‘benzo[b]pyridine’.
4. 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.
5. Shang, XF; Morris-Natschke, SL; Liu, YQ; Guo, X; Xu, XS; Goto, M; Li, JC; Yang, GZ; Lee, KH (May 2018). "Biologically
active quinoline and quinazoline alkaloids part I."Medicinal Research Reviews. 38 (3): 775-828.
doi:10.1002/med.21466. PMC 6421866. PMID 28902434.
6. Shang, Xiao-Fei; Morris-Natschke, Susan L.; Yang, Guan-Zhou; Liu, Ying-Qian; Guo, Xiao; Xu, Xiao-Shan; Goto, Masuo; Li,
Jun-Cai; Zhang, Ji-Yu; Lee, Kuo-Hsiung (September 2018). "Biologically active quinoline and quinazoline alkaloids part
II". Medicinal Research Reviews. 38 (5): 1614–1660. doi:10.1002/med.21492. PMC 6105521. PMID 29485730.
7. F. F. Runge (1834) "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. Jump up to: Gerd Collin; Hartmut Höke. "Quinoline and Isoquinoline". Ullmann's Encyclopedia of Industrial Chemistry
Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_465.
REFERENCE

25. 9. Gerhardt, Ch. (1842) "Untersuchungen über die organischen Basen" (Investigations of organic bases), Annalen der Chemie und
Pharmacie, 42 : 310-313. See also: (Editor) (1842) "Chinolein oder Chinoilin" (Quinoline or quinoilin), Annalen der Chemie und
Pharmacie, 44 : 279-280.
10. Initially, Hoffmann thought that Runge's Leukol and Gerhardt's Chinolein were distinct. (See: Hoffmann, August Wilhelm
(1843) "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) "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.)
11. O'Loughlin, Edward J.; Kehrmeyer, Staci R.; Sims, Gerald K. (1996). "Isolation, characterization, and substrate utilization of a
quinoline-degrading bacterium". International Biodeterioration & Biodegradation. 38 (2): 107. doi:10.1016/S0964-
8305(96)00032-7.
12. GRIBBLE, Gordon W.; HEALD, Peter W. (1975). "Reactions of Sodium Borohydride in Acidic Media; III. Reduction and
Alkylation of Quinoline and Isoquinoline with Carboxylic Acids". Synthesis. 1975 (10): 650–652. doi:10.1055/s-1975-
23871.ISSN0039-7881.
13. Xu, L.; Lam, K. H.; Ji, J.; Wu, J.; Fan, Q.-H.; Lo, W.-H.; Chan, A. S. C. Chem. Commun.2005, 1390.
14. Reetz, M. T.; Li, X. Chem. Commun. 2006, 2159.
15."QUINOLINE (BENZOPYRIDINE)". Chemicalland21.com. Retrieved 2012-06-14.
16.Jump up to: Chisholm, Hugh, ed. (1911). "Quinoline" . Encyclopædia Britannica. 22 (11th ed.). Cambridge University Press.
p. 759.
REFERENCE

26. THANK
YOU