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 (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 S_N2 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]