Bruylants reaction

Last updated

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 (c.f. cyanohydrin). It is useful for synthesizing phencyclidine 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

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 magnesium-halide Grignard reagents, though they are more prone than Grignards to attack the nitrile itself. [6]

References

  1. ↑ 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.
  2. ↑ Brother of Albert Bruylants  [ fr ], who was also a chemist
  3. ↑ Bruylants, P. (1924). Bull. Soc. Chim. Belg. 33: 467–478.{{cite journal}}: Missing or empty |title= (help)
  4. ↑ Mattalia, Jean-Marc Robert (2021). "The Bruylants and related reactions". Arkivoc: 1–19. doi: 10.24820/ark.5550190.p011.349 .
  5. ↑ 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.
  6. ↑ 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.


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.