Asinger reaction

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

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

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

References

1. Asinger, F.; Offermanns, H. (November 1967). "Syntheses with ketones, sulfur, and ammonia or amines at room temperature". Angewandte Chemie International Edition in English. 6 (11): 907–919. doi:10.1002/anie.196709071.
2. Asinger, F. (21 June 1956). "Über die gemeinsame Einwirkung von Schwefel und Ammoniak auf Ketone". Angewandte Chemie. 68 (12): 413. Bibcode:1956AngCh..68..413A. doi:10.1002/ange.19560681209.
3. Asinger, F.; Thiel, M. (26 November 1958). "Einfache Synthesen und chemisches Verhalten neuer heterocyclischer Ringsysteme". Angewandte Chemie. 70 (22–23): 667–683. Bibcode:1958AngCh..70..667A. doi:10.1002/ange.19580702202.
4. Drauz, Karlheinz; Koban, Hans Günter; Martens, Jürgen; Schwarze, Wolfgang (12 March 1985). "Phosphonic and Phosphinic Acid Analogs of Penicillamine". Liebigs Annalen der Chemie. 1985 (3): 448–452. doi:10.1002/jlac.198519850303.
5. Weigert, Wolfgang M.; Offermanns, Heribert; Scherberich, Paul (May 1975). "D-Penicillamin - Herstellung und Eigenschaften". Angewandte Chemie. 87 (10): 372–378. Bibcode:1975AngCh..87..372W. doi:10.1002/ange.19750871003.
6. Martens, Jürgen; Offermanns, Heribert; Scherberich, Paul (August 1981). "Einfache Synthese von racemischem Cystein". Angewandte Chemie. 93 (8): 680–683. Bibcode:1981AngCh..93..680M. doi:10.1002/ange.19810930808.

Literature

• Friedrich Asinger (1956). "Chemiker-Treffen Salzburg: Über die einfache und ergiebige Synthese von Thiazolonen". Angewandte Chemie. 68 (11): 377. doi:10.1002/ange.19560681109.
• Friedrich Asinger (1956). "Über die gemeinsame Einwirkung von Schwefel und Ammoniak auf Ketone". Angewandte Chemie. 68 (12): 413. Bibcode:1956AngCh..68..413A. doi:10.1002/ange.19560681209.
• Imre Schlemminger; Hans-Hermann Janknecht; Wolfgang Maison; Wolfgang Saak; Jürgen Martens (2000). "Synthesis of the first enantiomerically pure 3-thiazolines via Asinger reaction". Tetrahedron Letters. 41 (38): 7289–7292. doi:10.1016/S0040-4039(00)01266-1.