Asinger reaction

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Friedrich Asinger (1907-1999)

The Asinger reaction or Asinger thiazoline synthesis is a reaction from the field of organic chemistry . It was discovered by Friedrich Asinger during his forced stay in the Soviet Union - as part of the deportation of German scientists ( Operation Ossawakim ). The Asinger reaction is a multi-component reaction and is also classified as A-4CR (abbreviation for Asinger four-component reaction): elemental sulfur , an α-substitutable ketone or aldehyde , another carbonyl component and ammonia result in good yields of 3- thiazolines or mixtures several 3-thiazolines.

An example of the classic Asinger reaction with a ketone.
An example of the classic Asinger reaction with an aldehyde

Alternatives

Alternatively, 3-thiazolines can also be formed from α-mercaptoaldehydes or α-mercaptoketones, an oxo component (aldehyde or ketone) and ammonia. In order for the reaction to take place, at least one hydrogen atom must be bound to the α-carbon atom (carbon atom next to the carbonyl carbon atom) (both when reacting with an aldehyde and when reacting with a ketone).

mechanism

The mechanism with an aldehyde (R 3 = H) is shown as an example; alternatively, the reaction can also take place with a ketone (R 3 = organyl group , e.g. alkyl group ). This is analogous.

First step: A thiolation reaction forms an intermediate α-mercaptoaldehyde (R 3 = H) or an α-mercaptoketone (R 3 = organyl group). In α-thiolation, base catalysis - here in particular amine-catalyzed (through the use of ammonia) - replaces the hydrogen atom in the α position. The reaction is initiated by an aldehyde.

Formation of the α-mercaptoketone

Second step: The α-mercaptoaldehyde reacts irreversibly with a second aldehyde molecule and ammonia to form 3-thiazoline. The second aldehyde molecule enters the ring closure reaction as the “oxo component”. It is an α-amino-alkylation of an SH-acidic compound with subsequent cyclic stabilization by elimination of water .

mechanism

variants

A more universal variant of the Asinger reaction was developed at Degussa AG . An α-halogenated carbonyl component reacts with sodium hydrogen sulfide and generates an α-mercapto-carbonyl component ( thiol ) in situ , which further reacts directly with aldehydes or ketones and ammonia to form 3-thiazolines:

Asinger Reaction Chlor.svg

In the chemical industry, based on the Asinger reaction, multi-stage processes for the production of the drug D-penicillamine (penicillamine: R = methyl group) and DL - cysteine (R = H) have been developed and operated on an industrial scale.

Asinger reaction as the first step in the production of cysteine ​​or penicilliamine

The synthesis of 3-oxazolines (oxygen analogues of 3-thiazolines) takes place according to a variant of the Asinger reaction from 2- haloaldehydes , ammonia, sodium hydroxide solution and an oxo component (usually a ketone).

Individual evidence

  1. ↑ Friedrich Asinger : About the joint effect of sulfur and ammonia on ketones. In: Angewandte Chemie. 68, No. 12, 1956, pp. 413-413, doi : 10.1002 / anie.19560681209 .
  2. ↑ Organikum . 23rd edition, Wiley-VCH, 2009, ISBN 978-3-527-32292-3 , p. 434.
  3. ↑ Friedrich Asinger, Manfred Thiel: Simple syntheses and chemical behavior of new heterocyclic ring systems. In: Angewandte Chemie. 70, No. 22-23, 1958, pp. 667-683, doi : 10.1002 / anie.19580702202 .
  4. ↑ Karlheinz Drauz, Hans Günter Koban, Jürgen Martens, Werner Schwarze : Phosphonic and Phosphinic Acid Analogs of Penicillamine. In: Liebig's annals of chemistry . 1985, No. 3, 1985, pp. 448-452, doi : 10.1002 / jlac.198519850303 .
  5. ↑ Wolfgang M. Weigert, Heribert Offermanns , Paul Scherberich: D-penicillamine - production and properties. In: Angewandte Chemie. 87, No. 10, 1975, pp. 372-378, doi : 10.1002 / ange.19750871003 . English version in: Angewandte Chemie International Edition. 14, 1975, pp. 330-336.
  6. ↑ Jürgen Martens , Heribert Offermanns , Paul Scherberich: Simple synthesis of racemic cysteine. In: Angewandte Chemie. 93, No. 8, 1981, pp. 680-683, doi : 10.1002 / anie.19810930808 . English version in: Angewandte Chemie International Edition. 20, 1981, p. 668.
  7. ↑ Maya Weber, Jürgen Jakob and Jürgen Martens : Synthesis and reactivity of 3-oxazolines. In: Liebig's annals of chemistry. 1992, No. 1, 1992, pp. 1-6, doi : 10.1002 / jlac.199219920102 .

literature

  • Friedrich Asinger: Chemists' Meeting Salzburg: About the simple and efficient synthesis of thiazolines. In: Angewandte Chemie. 68, 1956, pp. 376-389, doi : 10.1002 / anie.19560681109 .
  • Friedrich Asinger: About the joint effect of sulfur and ammonia on ketones. In: Angewandte Chemie. 68, 1956, pp. 413-413, doi : 10.1002 / anie.19560681209 .
  • Imre Schlemminger, Hans-Hermann Janknecht, Wolfgang Maison, Wolfgang Saak, Jürgen Martens: Synthesis of the first enantiomerically pure 3-thiazolines via Asinger reaction. In: Tetrahedron Letters 41, 2000, pp. 7289-7292, doi : 10.1016 / S0040-4039 (00) 01266-1 .
  • Jürgen Martens, Hans-Herrmann Janknecht: Synthesis of 2-tert-butyl-3-thiazolines and studies on the diastereoselectivity of the Asinger reaction. In: Sulfur Letters. 11, 1990, pp. 263-270.

Web links

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