Bruylants reaction
In organic chemistry, the Bruylants reaction (sometimes misspelled Bruylant) is a substitution reaction in which a Grignard reagent replaces a nitrile on a carbon that also has an amino group. It is useful for synthesizing phenylcyclidine and related dissociative anesthetics.[1]
Unlike a traditional Grignard reaction where the nucleophile attacks the nitrile carbon, here the nitrile itself is lost as a leaving group. The reaction is named for Pierre Bruylants (1855–1950),[2] who first reported it in 1924.[3]
The reaction mechanism appears to involve ejection of the nitrile to form an iminium that is then attacked by the Grignard rather than a direct displacement such as an SN2 reaction. This accounts for the importance of the alpha amino group and the absence of stereoselectivity on chiral reaction sites.[4]
Modifications
[edit]1,2,3-Triazole and related heterocycles have been used as safer alternatives to the nitrile, as they avoid the typical use of cyanide to form the nitrile.[5]
Organolithium reagents can be used instead of the magesium-halide Grignard reagents, though they are more prone than Grignards to attack the nitrile itself.[6]
References
[edit]- ^ Morris, Hamilton; Wallach, Jason (2014). "From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs". Drug Testing and Analysis. 6 (7–8): 614–632. doi:10.1002/dta.1620. PMID 24678061.
- ^ Brother of Albert Bruylants, who was also a chemist
- ^ Bruylants, P. (1924). Bull. Soc. Chim. Belg. 33: 467–478.
{{cite journal}}: Missing or empty|title=(help) - ^ Mattalia, Jean-Marc Robert (2021). "The Bruylants and related reactions". Arkivoc: 1–19. doi:10.24820/ark.5550190.p011.349.
- ^ Prashad, Mahavir; Liu, Yugang; Har, Denis; Repič, Oljan; Blacklock, Thomas J. (2005). "1,2,3-Triazole as a safer and practical substitute for cyanide in the Bruylants reaction for the synthesis of tertiary amines containing tertiary alkyl or aryl groups". Tetrahedron Letters. 46 (33): 5455–5458. doi:10.1016/j.tetlet.2005.06.066.
- ^ Kalir, Asher; Edery, Habib; Pelah, Zvi; Balderman, D.; Porath, Gila (1969). "1-Phenylcycloalkylamine derivatives. II. Synthesis and pharmacological activity". Journal of Medicinal Chemistry. 12 (3): 473–477. doi:10.1021/jm00303a030. PMID 4977945.
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