Page 335 - Mechanism and Theory in Organic Chemistry

oximes (112) are allowed to rearrange in 180-enriched solvent, the product
amide contains the same percentage of 180 as the s01vent.l~~ Alkyl or aryl
migration, on the other hand, must be intramolecular, since a chiral migrating
group retains its chirality during the migration.158

The Hofmann Rearrangement159
In 1882 Hofmann discovered that when amides are treated with bromine in
basic solution, they are converted to amines with one carbon less than the
starting amide.160 He also isolated the N-bromo amine (114) and the isocyanate
(115) as intermediates on the reaction path. The mechanism in Equation 6.56
accounts for the products and the intermediates. This reaction (or the analogous
rearrangement of the N-chloro amine) is now known as the Hofmann rearrange-
ment or, because of its synthetic usefulness in eliminating a carbon atom, the
Hofmann degradation.

I I
Br- + 0--C=N-R HO-C-NHR - H2NR + C02 (6.56)
115
In a most convincing demonstration of the intramolecularity of the migra-
tion step, Wallis and Moyer carried out the Hofmann degradation on chiral
116. This compound can be prepared in optically active form because the groups
in the ortho position of the phenyl ring hinder the rotation that would convert
116 to its mirror image 117. During rearrangement 116 would lose chirality if the

116 117
migrating bond simply stretched enough to allow rotation about itself. However,
loss of chirality is not observed : 116 rearranges with retention of configuration.161
There is a question whether Equation 6.56 shows all the intermediates on
the reaction path. If, instead of rearrangement being concerted with loss of
halide ion as shown in Equation 6.56, the halide ion departed first, then a
nitrene162 would be formed as shown in Equation 6.57. To date no nitrene inter-

15' See note 149, p. 320.
158 (a) A. Campbell and J. Kenyon, J. Chem. Soc., 25 (1946); (b) J. Kenyon and D. P. Young, J.
Chem. Soc., 263 (1941).
159 E. S. Wallis and J. F. Lane, Org. Reactions, 3, 267 (1946).
160 A. W. Hofmann, Ber. Deut. Chem. Ges., 15, 762 (1882).
E. S. Wallis and W. W. Moyer, J. Amer. Chem. Soc., 55, 2598 (1933).
lB2 A "nitrene" is a nitrogen-containing compound in which the nitrogen has only a sextet of elec-
trons. Such a species is neutral but electron-deficient; cf. carbenes (Section 5.6).