Combes quinoline synthesis

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The Combes quinoline synthesis is a name reaction in organic chemistry . It was first published in 1888 by the French chemist Alphonse Combes (1854-1907). The reaction describes a possibility to synthesize quinoline derivatives from aniline and β- diketones :

R 1 , R 2 and R 3 are alkyl or aryl radicals which can be identical or different.

As acid may sulfuric acid or even better polyphosphoric be used.

mechanism

The reaction involves a condensation reaction between aniline and a β-diketone, followed by acid- catalyzed ring closure to a quinoline derivative. The radicals R 1 , R 2 and R 3 again correspond to an alkyl or aryl radical .

Mechanism of Combes quinoline synthesis

In this acid-catalyzed reaction, aniline (1) and a β-diketone 2 react via intermediate stages 3 and 4 to form the Schiff base 5 (see also: Imine production ). The protonation of the carbonyl group 5 to molecule 6 is followed by an electrophilic aromatic substitution via the intermediate 7 (only a mesomeric boundary structure is shown here) to the bicyclic compound 8. With elimination of water , another C = C double bond is formed and thus the quinoline derivative 9.

Since the ring closure (in the course of the electrophilic aromatic substitution) can take place at two different ortho positions , a mixture of two quinoline derivatives with the exchanged radicals R 1 and R 3 is formed .

See also

Individual evidence

  1. ↑ a b c d e Daniel Zerong Wang: Comprehensive Organic Name Reactions and Reagents . 1st edition. tape 1 (3 volumes). John Wiley & Sons , Hoboken (New Jersey) 2009, ISBN 978-0-471-70450-8 , Combes Quinoline Synthesis (Chapter 151), pp. 688-691 , doi : 10.1002 / 9780470638859.conrr151 .
  2. ↑ a b c László Kürti , Barbara Czakó: Strategic Applications of Named Reactions in Organic Synthesis . 1st edition. Elsevier Academic Press, Amsterdam 2005, ISBN 978-0-12-429785-2 , pp. 94-95 .
  3. ^ Francis William Bergstrom: Heterocyclic Nitrogen Compounds . Part IIA. Hexacyclic Compounds: Pyridines, Quinolines, and Isoquinolines. In: Chemical Reviews . tape 35 , no. 2 , 1944, pp. 77-277 , doi : 10.1021 / cr60111a001 .
  4. ↑ Alphonse Combes: Sur les synthèses dans la série quinoléique au moyen de l'acétylacétone et de ses dérivés . In: Bulletin de la Société chimique de Paris . tape 49 , 1888, pp. 89-92 ( Gallica summary on p. 66).
  5. ↑ a b Jie Jack Li: Name Reactions . A Collection of Detailed Reaction Mechanisms. 3. Edition. Springer-Verlag, Berlin Heidelberg 2006, ISBN 978-3-540-30030-4 , p. 131-132 .