Hantzsch synthesis of dihydropyridine

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The Hantzsch dihydropyridine synthesis (also Hantzsch's dihydropyridine synthesis ) is a name reaction in organic chemistry that was named after its discoverer Arthur Hantzsch (1857-1935). With this reaction 1,4-dihydropyridine or one of its derivatives is synthesized.

Name variants

In a simplified form, the reaction is also referred to as the Hantzsch pyridine synthesis , since the 1,4-dihydropyridine that is formed is mostly converted into aromatized pyridine . In the Streitwieser the variant Hantzsch reaction is used. The variant Hantzsch pyridine synthesis is a direct derivative of the English term.

Overview reaction

In this reaction, a β-keto carbonyl compound 1 , 4 , an aldehyde 3 and ammonia 2 (or a primary aliphatic amine ) are reacted with one another in a ratio of 2: 1: 1.

Overview of the Hantzschen dihydropyridine synthesis

mechanism

During the reaction, both the β-ketocarbonyl compound 1 and ammonia 2 and the β-ketocarbonyl compound 4 and the aldehyde 3 enter into a kind of Knoevenagel reaction . An enamine 6 is formed from ammonia . The aldehyde reacts to form an unsaturated carbonyl compound 7 . The first two reaction products 6 , 7 react in a kind of Michael addition to form a dihydropyridine or one of its derivatives 5 .

Mechanism of the Hantzschschen dihydropyridine synthesis

Alkyl or O-alkyl groups are used as the radical R 1 and alkyl or aryl groups are used as R 2 and R 3 .

The synthesis of pharmacologically relevant dihydropyridines is elegantly possible in this way. To get to nifedipine , for example , 2-nitrobenzaldehyde is used as the aldehyde component, methyl acetoacetate as the β-ketocarbonyl compound and ammonia .

Individual evidence

  1. ↑ Hans Beyer , Wolfgang Walter : Textbook of organic chemistry . 19th edition, S. Hirzel Verlag, Stuttgart 1981, ISBN 3-7776-0356-2 , p. 712.
  2. ^ Allinger , Cava , Don C. de Jongh , Carl R. Johnson , Norman A. Lebel , Stevens : Organic Chemistry . Walter de Gruyter, Berlin 1980, ISBN 3-11-004594-X , p. 1105.
  3. ^ Andrew Streitwieser , Clayton H. Heathcock : Organic Chemistry . Verlag Chemie, Weinheim 1980, ISBN 3-527-25810-8 , p. 1459: Hantzsch pyridine synthesis .
  4. ^ Andrew Streitwieser , Clayton H. Heathcock : Organic Chemistry . Verlag Chemie, Weinheim 1980, ISBN 3-527-25810-8 , p. 1286.
  5. ↑ K. Peter C. Vollhardt , Neil E. Schore: Organic chemistry . 4th edition, Wiley-VCH, Weinheim 2005, ISBN 978-3-527-31380-8 , pp. 1338, 1358.
  6. ↑ A. Hantzsch: Condensation products from aldehyde ammonia and ketone-like compounds . In: Reports of the German Chemical Society . tape 14 , no. 2 , July 1881, p. 1637–1638 , doi : 10.1002 / cber.18810140214 ( digitized on Gallica ).
  7. ↑ L. Kürti, B. Czakó: Strategic Applications Of Named Reactions In Organic Synthesis . Elsevier Academic Press, Burlington 2005, ISBN 0-08-057541-2 , pp. 194 .