Quinoline

THIS SLIDE HAVE GOOD CONTENT. THIS SLIDE CONTAIN INTRODUCTION, STRUCTURE, RESONANCE, AROMATICITY, PHYSICAL AND CHEMICAL PROPERTIES, SYNTHESIS AND APPLICATION OF QUINOLINE.

1. FUSED HETEROCYCLES WITH ONE HETEROATOMS QUINOLINE BY – VISHAL SINGH SOLANKI A.P. AT IDEAL INSTITUTE, POSHERI, WADA, PALGHAR, M.H. EMAIL – [email protected]

2. QUINOLINE

3. Quinoline  is a heterocyclic aromatic organic compound with the chemical formula C 9 H 7 N. 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 C 9 H 7 N. 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 C 9 H 7 N 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

23. ANY QUESTION ?

24.   https://www.researchgate.net/publication/325080072_UNIT_-V_Heterocyclic_Chemistry_Quinoline_Isoquinoline_and_Indole https://en.wikipedia.org/wiki/Quinoline 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’. 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. 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 .   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 .  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.)   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.  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.  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.)   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 .   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 .  Xu, L.; Lam, K. H.; Ji, J.; Wu, J.; Fan, Q.-H.; Lo, W.-H.; Chan, A. S. C.  Chem. Commun. 2005 , 1390.   Reetz , M. T.; Li, X.  Chem. Commun .   2006 , 2159. "QUINOLINE (BENZOPYRIDINE)" . Chemicalland21.com. Retrieved 2012-06-14. Jump up to:   Chisholm, Hugh, ed. (1911).  "Quinoline"  .  Encyclopædia Britannica .  22  (11th ed.). Cambridge University Press. p. 759 . REFERENCE

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