| Gewald reaction | |
|---|---|
| Named after | Karl Gewald |
| Reaction type | Ring forming reaction |
| Identifiers | |
| Organic Chemistry Portal | gewald-reaction |
TheGewald reaction (or the Gewald aminothiophene synthesis) is anorganic reaction involving thecondensation of aketone (oraldehyde when R2 = H) with a α-cyanoester in the presence of elementalsulfur and base to give a poly-substituted 2-amino-thiophene.[1][2]
The reaction is named after the German chemistKarl Gewald [de].[3][4][5]
The reaction mechanism of the Gewald reaction was elucidated 30 years after the reaction was discovered.[6] The first step is aKnoevenagel condensation between the ketone (1) and the α-cyanoester (2) to produce the stable intermediate3. The mechanism of the addition of the elemental sulfur is unknown. It is postulated to proceed through intermediate4. Cyclization andtautomerization will produce the desired product (6).
Microwave irradiation has been shown beneficial to reaction yields and times.[7]
In one variation of the Gewald reaction a3-acetyl-2-aminothiophene is synthesized starting from adithiane (an adduct of sulfur andacetone if R = CH3 or acetaldehyde if R = H) and the sodium salt ofcyanoacetone which in itself is very unstable:[8]
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