LECTURE 1
3. Reactions: Electrophilic Substitution
The general equation for this reaction is:
+ EX + HX
Fig. 1
The ready availability of the π-electrons makes benzene rings
nucleophilic i.e. they are susceptible to attack by electrophiles, despite
the stability of the ring.
(a) Arenium Ion Mechanism:
The reaction passes through an intermediate which is variously called
the σ-complex, the Wheland intermediate or the arenium ion:
H
E E
E -H
Fig. 2
Although the Wheland intermediate is stabilised by resonance
H H H H
E E E E
Fig. 3
we have clearly lost the aromatic stabilisation of the starting material
and hence the addition of the electrophile is going to be the slow step
(rds = rate determining step). The second step will be fast since we
regenerate the aromatic system by loss of the proton.
The evidence for the arenium ion mechanism is
• No deuterium/hydrogen isotope effect in most cases. If the
hydrogen departed before the electrophile added or if the arrival of
the electrophile and the departure of the proton were simultaneous
then we would expect an isotope effect on the rate of reaction if we
replace H by its more massive isotope D (deuterated substrates
undergo substitution more slowly than protonated species when C
– H(D) is involved in the rate determining step because the C – H
bond is weaker than the C – D bond). Thus the lack of an isotope
effect means that the proton is lost after the rds.
• Isolation of an arenium ion. For example:
H
EtF, BF3 warm
Et Et
o
-80 C -HBF4
m.p. -15oC
Fig. 4
Even the simplest arenium ion from benzene has been detected by
NMR at low temperatures (-134 oC).
The most common types of electrophile are illustrated in the table on
the following page. The last reaction on the list, namely sulphonation,
is reversible. Heating benzene-sulphonic acid in dilute sulphuric acid
or water converts it back to benzene.
Product Electrophilic Species (boxed) Reaction Name
O O
NO2 H2SO4
HO N H2O N O N O Nitration
O O HSO4
HSO4
Br
Bromination
Br Br FeBr3 Br FeBr4
R
R Cl AlCl3 R AlCl4 Friedel-Crafts
Alkylation
O O
Friedel-Crafts
Cl AlCl3 R C O AlCl4
R Acylation
R
O H
Vilsmaier-Haack
Cl Formylation
H Me2NCHO + POCl3
Me2N
Cl
HgOAc
AcO HgOAc Mercuration
D DSO4 Deuteration
SO3H
SO3 Sulphonation
The mechanism for the formation of the Vilsmaier-Haack formylating
agent is as follows:
Cl
N N
O O
Cl2P(O)
Cl2P(O) Cl
Cl
Cl
N
N
OP(O)Cl2 O
Cl2P(O)
Fig. 5
(b) Reactivity and Orientation: definitions
What do we mean by these terms? If we have a mono-substituted
benzene instead of benzene itself then attack by the electrophile can
occur in four possible positions (ipso, ortho, meta and para):
R
ipso
ortho(o) ortho (o)
meta (m) meta (m)
para (p)
Fig. 6
Which of these sites is attacked is called the Orientation of the
reaction.
When compared with benzene, the rate of the reaction of a mono-
substituted benzene may be slower or faster. This is the Reactivity of
the reaction. If the reaction is slower the substituent is said to
deactivate the ring; if faster it activates it. The following illustrate the
differences in orientation and reactivity that we may observe:
NO2
Relative Rate
HNO3 ,
H2SO4 1
Me Me Me
NO2
HNO3 ,
+ 23
H2SO4
NO2 NO2 NO2
HNO3 ,
6 x 10-8
H2SO4
NO2
Fig. 7
Thus toluene reacts 23 times faster than benzene and gives a mixture of
ortho and para products whereas nitrobenzene is very much less
reactive and only gives the meta product.
(c) Reactivity and Orientation: ortho / para – and meta – directors
We must now attempt to classify the groups, R, according to their
influence on both reactivity and orientation. Two properties of R have
a major influence, namely, inductive (I) effects and resonance
(sometimes known by the older term, mesomeric)(Re or M) effects.
The groups, R, fall into the following categories:
• O-, NR2, NHR, NH2, OH, OR, NHCOR, OCOR
• NO2, CN, SO3H, CHO, COR, CO2H, CONH2
• R
• CO2-
• +NR3, +NH3, CCl3, CF3
• F, Cl, Br, I
We will now discuss each of these categories in turn.
Category 1: O-, NR2, NHR, NH2, OH, OR, NHCOR, OCOR
In each case the atom directly attached to the benzene ring is more
electronegative than carbon and, therefore, each group has a inductive
electron withdrawing, -I, effect (the only exception to this is the O-
group where the negative charge repels electrons in the C – O bond).
However, countering that effect is a strong +Re effect because each
group has a lone pair of electrons which it is able to donate to the ring
by resonance:
X X X X
For O-, NR2, NHR, NH2, OH, OR +Re >> -I
Fig. 8 For NHCOR, OCOR +Re > -I
Every one of these groups, therefore, makes the ring more electron rich
than benzene and thereby makes the ring more susceptible to attack by
electrophiles i.e. aromatics bearing these groups react faster then
benzene and the groups are said to be activating, strongly so for O-,
NR2, NHR, NH2, OH, OR and moderately so for NHCOR, OCOR. The
latter are less activating than the former because the lone pairs on N or
O are to some extent also being delocalised into the carbonyls:
X R X = NH or O
Fig. 9
With regard to the orientation we may explain the product distribution
by the charge build up in the starting aromatic, by the stabilisation of
the Wheland intermediate or by both. In these cases the resonance
effect builds up negative charge only on the ortho and para positions
in the starting material as shown above and, therefore, we would
expect the electrophile to attack those positions selectively.
The same conclusion is reached if we look at the stabilisation of the
Wheland intermediate after such attack compared to attack at the meta
position (see next page).
Notice that in the attack at either ortho or para positions the Wheland
intermediate has an extra canonical form in which the positive charge
may be delocalised onto the atom X by involvement of the lone pair on
X; this is not possible on attack at the meta position and hence this
latter intermediate is less stable than those from either ortho or para
attack. Thus this category of groups is ortho / para (o/p) directing as
well as activating.
