Page 398 - Mechanism and Theory in Organic Chemistry

Electrophilic Aromatic Substitution 385
the electrophile first forms some sort of intermediate complex with the aromatic
ring and subsequently a proton is lost (Equation 7.70).

complex

66
In experiments of major importance, first published in 1950, Melander
found that in the nitration and bromination of a number of benzene derivatives
the tritium isotope effect (k,/k,) is not 10-20 as is to be expected if carbon-
hydrogen bond breaking occurs in the rate-determining step, but rather is less
than 1.3. The direct displacement mechanism was thus ruled out, and the two-
step mechanism of Equation 7.70 with the first step rate-determining was
imp1i~ated.l~~
Examination of the rate equation for the mechanism of Equation 7.70
reveals the probable origin of the small isotope effects observed by Melander.
Using the steady-state approximation for the concentration of the intermediate
complex (66), the observed rate is calculated to be

rate = [Ar][E +I kl(k,[Bllk-1)
1 + (kzBlk-1)
When the second step is very fast compared to the reverse of the first step-that
is, when k,[B]/k- , >> 1-Equation 7.71 can be simplified to
rate = k, [Ar] [E +] (7.72)
In this case a primary isotope effect of I .O would be expected, since only the rate
constant for the first step, in which no bond breaking occurs, is involved in the
rate equation. When the reverse of the first step is very fast compared to the
second step-that is, k,[B]/k-, << 1-then the observed rate is linear with k, as
shown in Equation 7.73.
k~kz[B]
rate = [Ar] [E +I -
k- 1
In this case a large isotope effect would be expected. If, however, k,[B] z k-,,
then Equation 7.71 cannot be simplified, and the magnitude of k, will affect the
overall rate albeit in a less than linear way. Then, even if k, > k,, some isotope
effect should be observed. The small isotope effect of Melander's experiments
make it appear that the first step is slower than the second, but that k-, competes
favorably with k,. When the second step becomes kinetically important in spite
of the first step being the slow step, we have an example of the partitioning efect-
so-called because the kinetic significance of the second step arises from the way
in which the intermediate partitions itself. Since 1950 a very large number of
electrophilic substitutions have been examined for isotope effects; in the absence
of special circumstances (see below), the isotope effects found are usually very
~ma11.l~~

'" 7. Melander, Ark. Kemi, 2, 211 (1950).
158 For reviews, see note 130(c) and H. Zollinger, Adv. Phys. Org. Chem., 2, 163 (1964).