Blaise reaction
The Blaise reaction is an organic reaction that forms a β-ketoester from the reaction of zinc metal with an α-bromoester and a nitrile. This reaction was first reported by Edmond Blaise in 1901[1].
The mechanism of the Blaise reaction involves the formation of an organozinc complex. 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) product is revealed by work-up. If the β-ketoester is the desired product, addition of 1 M hydrochloric acid hydrolyzes the β-enamino ester to turn the enamino into a ketone, forming the β-ketoester[1].
The Blaise reaction is an important carbon–carbon bond-forming reaction that has found its rightful place in synthetic organic chemistry in recent years[3]. It has been noted that free hydroxyl groups can be tolerated in the course of this reaction, which is surprising for reactions of organometallic halides[1].
The efficiency of the Blaise reaction is partially limited by the occasional formation of nitrogen-containing byproducts. For example, the zinc intermediate may undergo partial hydrolysis to the moderately stable enamine, or it can react further acting as a nucleophile with the nitrile[2].
Despite these limitations, the Blaise reaction has been used in the synthesis of various natural and non-natural products, and has been improved by various modifications in reaction conditions[6]. It has also been used as a tool for drug discovery, enabling the synthesis of valuable intermediates and heterocycles[10].
Citations:
[1] https://en.wikipedia.org/wiki/Blaise_reaction
[2] https://science-of-synthesis.thieme.com/app/text/?id=SD-020-01286
[3] https://www.sciencedirect.com/topics/chemistry/blaise-reaction
[4] https://www.sciencedirect.com/science/article/pii/S0223523401012302
[5] https://academic-accelerator.com/encyclopedia/blaise-reaction
[6] https://www.thevespiary.org/library/Files_Uploaded_by_Users/no1uno/pdf/Medicinal/Amino.Acids/Blaise.Reaction.pdf
[7] https://www.researchgate.net/publication/233950747_The_Blaise_reaction
[8] https://www.drugfuture.com/OrganicNameReactions/ONR46.htm
[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606174/
[10] https://pubs.rsc.org/en/content/articlelanding/2017/gc/c6gc02619b
[11] https://pubs.acs.org/doi/abs/10.1021/jo900324d
[12] https://www.rsc.org/suppdata/d0/nj/d0nj00231c/d0nj00231c1.pdf
[13] https://pubs.acs.org/doi/10.1021/jo900324d
[14] https://escholarship.org/content/qt6394z6nc/qt6394z6nc_noSplash_8b96ea98348f8221255451f35cbda1ed.pdf?t=quwcwd
[15] https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/ejoc.201700868
[16] https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0037-1610171
[17] https://www.merriam-webster.com/dictionary/blas%C3%A9
[18] https://academic-accelerator.com/encyclopedia/blaise-ketone-synthesis
[19] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982458/
[20] https://www.thoughtco.com/name-reactions-in-organic-chemistry-3999996
[21] https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0035-1561973
[22] https://www.sciencedirect.com/topics/chemistry/reformatsky-reaction