| Blaise reaction | |
|---|---|
| Named after | Edmond E. Blaise |
| Reaction type | Coupling reaction |
| Identifiers | |
| Organic Chemistry Portal | blaise-reaction |
| RSC ontology ID | RXNO:0000237 |
TheBlaise reaction is anorganic reaction that forms a β-ketoester from the reaction ofzinc metal with anα-bromoester and anitrile.[1][2][3] The reaction was first reported byEdmond Blaise (1872–1939) in 1901. The final intermediate is a metaloimine, which is thenhydrolyzed to give the desired β-ketoester.[4]
Bulkyaliphatic esters tend to give higher yields. Steven Hannick andYoshito Kishi have developed an improved procedure.[5]
It has been noted[6][7] that free hydroxyl groups can be tolerated in the course of this reaction, which is surprising for reactions of organometallic halides.
The mechanism of the Blaise reaction involves the formation of an organozinc complex with the bromine alpha to the ester carbonyl. This makes the alpha carbon nucleophilic, allowing it to attack the electrophilic carbon of the nitrile. The negative nitrile nitrogen resulting from this attack complexes with the zinc monobromide cation. The β-enamino ester (tautomer of the imine intermediate pictured above) product is revealed by work-up with 50% K2CO3 aq. If the β-ketoester is the desired product, addition of 1 Mhydrochloric acid hydrolyzes the β-enamino ester to turn the enamino into a ketone, forming the β-ketoester.
