The Neber rearrangement is a base-induced rearrangement of O-acylated ketoximes to the corresponding α-amino ketones. It was discovered in 1926 by Neber and Friedolsheim during their investigation of the Beckmann rearrangement. The Neber rearrangement has since become an important synthetic tool for synthesizing heterocycles that use amino ketones as intermediates. It proceeds through an alkoxide-induced rearrangement of the O-acylated ketoxime to form an α-amino ketone product. There are some limitations in that aldoximes do not undergo the rearrangement and substrates generally require a methylene group in the α-position.

1. BY
Dr. Gurumeet.C.Wadhawa
DEPARTMENT OF CHEMISTRY
K. B. P. College,Vashi,Navimumbai
Neber Rearrangement

2. In 1926, during the investigation of the Beckmann rearrangement, P.W. Neber
and A. Friedolsheim reported that the successive treatment of ketoxime
tosylates with potassium ethoxide, acetic acid, and hydrochloric acid yielded
the hydrochloride salts of α-amino ketones.
The base-induced rearrangement of O-acylated ketoximes to the
corresponding α-amino ketones is known as the Neber rearrangement. Since
its discovery, the rearrangement has become an important synthetic tool in the
synthesis of heterocycles in which amino ketones are used as key
intermediates.

5. 1) acylated ketoximes derived from both acyclic and cyclic ketones can be
used;
2) the required oximes are readily prepared from the ketones by reacting
them with hydroxylamine under acidic conditions;
3) O-acylation of the oximes is conducted using acyl halides or anhydrides
in the presence of a mild base (e.g., pyridine);
4) the rearrangement is usually carried out in an alcohol solution containing
equimolar quantities of an alkali alkoxide;
5) when two methylene groups are available at the α- and α'- positions, the
rearrangement mainly gives rise to a product in which the amino group is
located on the more electrophilic carbon;
6) the rearrangement is not stereospecific, since the stereochemistry of the
substrate (syn or anti) usually does not influence the outcome of the
reaction, and this is in sharp contrast with the stereospecificity of the
Beckmann rearrangement; and
7) the product amino ketones have a tendency to dimerize, so they often
need to
be prepared in a protected form as their amino acetals or hydrochloride
salts (e.g., the amino acetals are prepared from the 2H-azirine
intermediates by treatment with acidic alcohols).
General
Features

6. There are a few limitations to the Neber rearrangement:
1) O-acylated aldoximes do not yield α-amino ketones upon treatment
with base, but rather undergo E2 elimination to afford the
corresponding nitriles or isonitriles; and
2) the substrate must have a methylene group in the α-position in the
overwhelming majority of the cases. Other types of compounds
having at least one α-hydrogen atom also undergo the Neber
rearrangement upon treatment with base: 1) ketone
dimethylhydrazonium halides;20 2)
N,N-dichloro-sec-alkyl amines;21,22 3) N-chloroimines;12 and 4) N-
chloroimidates

14. References
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