Asinger reaction

The Asinger-reaction (sometimes referred to as the Asinger-4 component reaction or A-4CR for short) is a multicomponent reaction for the synthesis of 3-thiazolines and other related heterocycles.^[1] It is named after Friedrich Asinger who first reported it in 1956.^[2]

Asinger-reaction using ketones

Asinger-reaction using aldehydes

Asinger reaction
Named after	Friedrich Asinger
Reaction type	Ring forming reaction
Identifiers
RSC ontology ID	RXNO:0000688

Process

An α-halogenated carbonyl-component reacts with sodium hydrosulfide (NaSH) and forms a Thiol in situ. The thiol reacts directly with another carbonyl component and ammonia to form a thiazoline. The reaction works also by using elemental sulphur, an α–substituted ketone, another carbonyl component and ammonia; in this case, a mixture of products is formed.

The formation of 3-thiazolines also occurs by using α-thioaldehyde or α-thioketone and ammonia.^[3]

A simplified route of the Asinger-reaction was developed at Degussa. An α-halogenated carbonyl compound reacts with sodium hydrosulfide (NaSH) and forms a thiol in situ which reacts directly with aldehydes or ketones and ammonia to 3-thiazolines.^[4] The chemical industry developed based on the Asinger-reaction multi stage processes for the production of pharmaceuticals like D-penicillamine^[5] and the aminoacid DL-cysteine.^[6]

Synthesis of penicillamine by the Asinger reaction