Level 3 – Case 39
264
IBX
O
I
O
O
HO
O
O
I
O
O O
HO
12
Scheme 39.5
Which is the rate-determining step?
The kinetic experiments were run to decide whether the rate-determining step
of the reaction was the SET (formation of radical cation I) or the radical cyclization step (transformation of II into III). The first set of data was obtained from
aryl-substituted anilides 7 (Fig. 39.1), in order to get information about the influence of the electronic effects on the reaction rate and hence about the possible
formation of a radical cation in the slow step.
N
H
O
IBX
N
H
O
1
SET
slow ?
I
SET step as rate-determining
R
R
The experimental results indicate that the IBX-mediated cyclization of anilides
is sensitive to the electronic character of the substituents in position para of the
anilide ring. In fact the reaction rate increases with the presence of electrondonating groups. These data are indicating a lower electron density in the transition state of the slow step of the reaction, relative to the initial ground state of the
substrate. In addition, the development of positive charge in the transition state is
confirmed by the fact that the Hammett plot shows a negative slope and by the excellent correlation with V
+ parameters (through conjugation).
We can conclude that the sensitivity of the reaction rate to the electronic effects
supports the development of positive charge in the transition state. This is in
agreement with the assumption that the SET from the amide aromatic ring to the
iodine reagent (leading to radical-cation I) is the rate-determining step of the reaction.
However, is this evidence sufficient to discard the radical cyclization step (II to
III) as rate-determining?