View source for Chemistry:Blaise reaction

{{Reactionbox
|Name = Blaise reaction
|Type = Coupling reaction
|NamedAfter = Edmond E. Blaise
|Section3 = {{Reactionbox Identifiers
| OrganicChemistryNamed = blaise-reaction
| RSC_ontology_id = 0000237
}}
}}
The '''Blaise reaction''' is an [[Chemistry:Organic reaction|organic reaction]] that forms a β-ketoester from the reaction of [[Chemistry:Zinc|zinc]] metal with a [[Chemistry:Haloketone|α-bromoester]] and a [[Chemistry:Nitrile|nitrile]].{{Ref|Blaise1901}}{{Ref|OS1955}}{{Ref|Rao2008}} The reaction was first reported by '''Edmond Blaise''' (1872–1939) in 1901. The final intermediate is a metaloimine, which is then hydrolyzed to give the desired β-ketoester.{{Ref|Cason1953}}

[[Image:Blaise Reaction Scheme.png|center|650px|The Blaise reaction]]

Bulky aliphatic esters tend to give higher yields. Steven Hannick and Yoshito Kishi have developed an improved procedure.{{Ref|Hannick1983}}

It has been noted{{Ref|Hannick1983}}{{Ref|Wang2005}} that free hydroxyl groups can be tolerated in the course of this reaction, which is surprising for reactions of organometallic halides.

==Mechanism==
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% K<sub>2</sub>CO<sub>3</sub> aq.  If the β-ketoester is the desired product, addition of 1 M [[Chemistry:Hydrochloric acid|hydrochloric acid]] hydrolyzes the β-enamino ester to turn the enamino into a ketone, forming the β-ketoester.

[[File:BlaiseRxnMech.svg|center|650px|Blaise Rxn Mechanism]]

==See also==
*[[Chemistry:Blaise ketone synthesis|Blaise ketone synthesis]]
*[[Chemistry:Reformatsky reaction|Reformatsky reaction]]
==References==
# {{Note|Blaise1901}} Edmond E. Blaise; ''Compt. Rend.'' '''1901''', ''132'', 478.
# {{Note|OS1955}} Rinehart, K. L., Jr. ''[[Chemistry:Organic Syntheses|Organic Syntheses]]'', Coll. Vol. 4, p.&nbsp;120 (1963); Vol. 35, p.&nbsp;15 (1955). ([https://web.archive.org/web/20120716191501/http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0120 Article])
# {{Note|Rao2008}} Rao, H. S. P.; Rafi, S.; Padmavathy, K. ''Tetrahedron'' '''2008''', ''64'', 8037-8043. (Review)
# {{Note|Cason1953}} Cason, J.; Rinehart, K. L., Jr.; Thorston, S. D., Jr. ''J. Org. Chem.'' '''1953''', ''18'', 1594. ({{doi|10.1021/jo50017a022}})
# {{Note|Hannick1983}} Hannick, S. M.; Kishi, Y. ''J. Org. Chem.'' '''1983''', ''48'', 3833. ({{doi|10.1021/jo00169a053}})
# {{Ref|Marko2007}} Marko, I.E. ''J. Am. Chem. Soc.'' '''2007''', ASAP {{doi|10.1021/ja0691728}}
# {{Ref|Wang2005}} Wang, D.; Yue, J.-M. ''[[Chemistry:Synlett|Synlett]]'' '''2005''', 2077-2079.

== External links ==
* [https://www.organic-chemistry.org/namedreactions/blaise-reaction.shtm Blaise Reaction - Details and Recent Literature]
{{Organic reactions}}
[[Category:Addition reactions]]
[[Category:Carbon-carbon bond forming reactions]]
[[Category:Name reactions]]

{{Sourceattribution|Blaise reaction}}