Asinger reaction

The Asinger reaction or Asinger thiazoline synthesis is a reaction from the field of organic chemistry. It was by Friedrich Asinger during his enforced sojourn in the Soviet Union - discovered - in the deportation of German scientists (Action Ossoawiachim ). The Asinger reaction is one of the multi-component reactions and (short for Asinger four-component reaction) classified as an A - 4CR: From elemental sulfur, an α - substitutable ketone or aldehyde, an additional carbonyl and ammonia are formed in good yield 3- thiazoline or mixtures of several 3- thiazoline.

Alternatives

Alternatively, 3- thiazoline also from α - Mercaptoaldehyden or α - mercapto ketones, an oxo component (aldehyde or ketone ) and ammonia occur .. In order for the reaction to proceed must be bound to the α - carbon atom ( carbon atom adjacent to the carbonyl carbon atom ) at least one hydrogen atom be (for both the reaction with an aldehyde and a ketone with at )

Mechanism

By way of example, the mechanism is shown with an aldehyde, Alternatively, the reaction may also take place with a ketone. This is similar.

First step: A thiolization formed intermediate a α - mercapto. At the α - base catalysis is thiolation - here specifically aminkatalysiert ( through the use of ammonia), - the H- atom is replaced in the α -position. The reaction is initiated by an aldehyde.

Second step: The α - mercapto irreversibly reacts with aldehyde and ammonia to 3- thiazoline. The aldehyde occurs here as oxo component in the ring-closing reaction a. There is an α -amino- alkylation of SH -acidic compound with the following cyclic stabilization by water leakage.

Variants

A more universal version of Asinger reaction was developed by Degussa AG. Thereby reacting an α - halogenated carbonyl component with NaHS and generated in situ α -mercapto- carbonyl component ( thiol ), further directly react with aldehydes or ketones and ammonia to give 3- thiazolines:

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

The synthesis of 3 - oxazolines (oxygen analogs of 3- thiazolines ) are prepared by a variant of Asinger reaction of 2- haloaldehydes, ammonia, sodium hydroxide and oxo component (usually a ketone ).