Page 794 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

is the rate-determining step. When formation of the active electrophile is the rate- 777
determining step, the concentration of the aromatic reactant no longer appears in
the observed rate expression. Under these conditions, different aromatic substrates SECTION 9.1
undergo nitration at the same rate, corresponding to the rate of formation of the active Electrophilic Aromatic
Substitution Reactions
electrophile.
An important general point to be drawn from the specific case of nitration is
that the active electrophile is usually some species that is more reactive than the
added reagents. The active electrophile is formed from the reagents by a subsequent
reaction, often involving a Brønsted or Lewis acid. One goal of mechanistic study is
to determine the identity of the active electrophile, the formation of which may or may
not be the rate-determining step. Scheme 9.1 indicates the structure of some of the
electrophilic species that are involved in EAS processes and the reactions involved in
their formation.
There are several lines of evidence pointing to formation of complexes as inter-
mediates in EAS. One approach involves measurement of isotope effects on the rate
of substitution. If removal of the proton at the site of substitution is concerted with the
introduction of the electrophile, a primary isotope effect is expected when electrophilic
attack on the ring is rate determining. This is not the case for nitration. Nitration of
aromatic substrates partially labeled by tritium shows no selectivity between protium-
7
and tritium-substituted sites. Similarly, the rate of nitration of nitrobenzene is identical
to that of penta-deuterio-nitrobenzene. 8
The lack of a primary isotope effect indicates that the proton is lost in a fast step
following the rate-determining step, which means that proton loss must occur from
some intermediate that is formed before the cleavage of the C−H bond begins. The
-complex intermediate fits this requirement. There are some electrophilic aromatic
substitution reactions that show k /k values between 1 and 2 and there are a few
H D
9
others that are in the range indicating a primary isotope effect. The existence of these
isotope effects is compatible with the general mechanism if the proton removal is
rate limiting (or partially rate limiting). Many of the modest kinetic isotope effects
(k /k ∼ 1 2−2 0) have been interpreted in terms of comparable rates for formation
H D
and deprotonation of the -complex intermediate.
The case for the cyclohexadienylium ion intermediates is further strengthened by
numerous studies showing that such cations can exist as stable entities under suitable
conditions. Substituted cyclohexadienylium ions can be observed by NMR under stable
ion conditions. They are formed by protonation of the aromatic reactant. 10

F F
SO + –
+ HF – SbF 5 2 SbF 6
H H
Ref. 11

7 L. Melander, Acta Chem. Scand., 3, 95 (1949); Arkiv Kemi., 2, 211 (1950).
8 T. G. Bonner, F. Bower, and G. Williams, J. Chem. Soc., 2650 (1953).
9
H. Zollinger, Adv. Phys. Org. Chem., 2, 163 (1964).
10 G. A. Olah, R. H. Schlosberg, R. D. Porter, Y. K. Mo, D. P. Kelly, and G. Mateescu, J. Am. Chem.
Soc., 94, 2034 (1972).
11
G. A. Olah and T. E. Kiovsky, J. Am. Chem. Soc., 89, 5692 (1967).