One of the most important
reactions of arenes is electrophilic
aromatic substitution, in which an electrophile reacts with the ring,
forming a new bond to a ring carbon with the loss of one hydrogen. In general,
these reactions require a Lewis acid
catalyst, as shown below for the reaction of bromine with benzene, catalyzed by
FeBr3. The role of the FeBr3 is to
complex the bromine to form a bromonium cation-like species (which is often
simply referred to as Br+) which is the actual electrophilic agent.
j(BENCENO) + Br2/
FeBr3 è j-Br
This electrophile first forms a
loose complex with the p-cloud, which rearranges to a cationic sigma-complex,
in which the electrophile is directly bonded to a ring carbon. Since the ring
is a conjugated system, the cationic charge which forms on the adjacent carbon
is delocalized over the ring,
with partial positive charge developing on the carbons which are ortho- and para- to the position where
the electrophile bonded. Loss of H+ from the
sigma-complex regenerates the aromatic p-system (with its associated
stability), and gives bromobenzene and HBr as the final products.
Chlorination proceeds by a
similar mechanism; for iodination, c/CuCl2 is typically
utilized to generate the electrophilic I+ cation.
Arenes can also be nitrated by a
similar mechanism using a mixture of nitric and sulfuric acids to generate the
electrophile NO2+, which adds to the ring to form a sigma complex, and
looses a proton to give the nitro compound.
j (BENCENO) + HNO3
/H2SO4 ==è j- NO2
Fuming sulfuric acid (H2SO4 saturated
with SO3) contains an equilibrium concentration of SO3H+, which is a
strongly electrophilic agent. The final product of the addition of SO3H+ to the ring
is the aryl sulfonic acid.
j + H2SO4 + SO3 è j- SO3 H
Perhaps the most notable (and
useful) example of electrophilic aromatic substitution is the introduction of
alkyl groups using the Friedel-Crafts
reaction. In this reaction, a Lewis acid complexes with an alkyl halide
to give a species with electrophilic character on the carbon of the alkyl
halide. This then reacts by the standard mechanism to give an intermediate
sigma-complex, and the alkylated benzene as the final product.
j(BENCENO) + RCl ==è j-CR + HCl
There are several limitations of
the Friedel-Crafts alkylation reaction, as shown below. Summarizing, only alkyl
halides can be utilized (not aryl- or vinyl halides); the ring must be
activated, since the electrophile is generally less reactive than those
encountered previously; multiple substitutions are possible, and perhaps most
important, since the carbon of the
alkyl halide has carbocation character, rearrangements often occur. In
general this means that an alkyl halide such as 1-bromopropane is not suitable
in this reaction, since it would be prone to rearrange to the more stable
isopropyl carbocation.
LIMITACIONES A LA ALQUILACION DE FRIEDEL-CRAFTS:
(a)
La reacción
se limita a haluros de alquilo, los haluros de arenos o de vinil no reaccionan.
(b)
La reaccion
no ocurre en anillos que contienen grupos atractores fuertes de electrones.
Ej: NO2- , -CN, -SO3H , -CHO, -COR, -COOH , -COOR , -NR3+.
(c)
Ocurren
reagrupamiento de los carbocationes, especialmente los haluros de alquilo
primarios.
REACCIONES DE ACILACION
j(BENCENO) + RCOCl ==è j-COR + HCl
A derivative of the
Friedel-Crafts alkylation is the Friedel-Crafts acylation reaction in which the
arene is converted to an aryl ketone. The electrophile in this reaction is an
acylium ion-like species which is formed by reaction of an acid halide, or an
acid anhydride, with the Lewis acid. Unlike the alkylation reaction,
rearrangements do not occur (the acylium cation is a very stable,
resonance-stabilized carbocation), although an activated ring is still
required.
When electrophilic aromatic
substitution occurs on a ring already bearing one or more substituent, the
nature of that substituent will impact both the rate of the reaction and the regiochemistry of the reaction (where
on the ring the substitution occurs). In the table shown below, activating substituents will react
faster than benzene itself, and deactivating
substituents will react more slowly. Further, substituents are grouped into two
categories; ortho- or para- directing,
and meta-directing.
A substituent is activating if
it releases electron density into the ring either inductively, or through
resonance (the electrophile is, after all, looking for electrons; the more
electron density, the faster the reaction). The orientation effect is seen by
considering the family of resonance forms which can be drawn for a substituent
such as an alkoxy group; these clearly show enhanced electron density localized
ortho- and para- to the point of attachment.
Meta-directing substituents such
as the nitro group can be seen to function by removing electron density from the ring ortho- and para-
to themselves, leaving only the meta-positions
with sufficient electron density to support the electrophilic
(electron-seeking) reaction. Thus, meta-directing
substituents don't really activate the meta-positions
towards substitution, they deactivate
everywhere else.
Halogens are somewhat unique in
that they deactivate inductively (and are therefore less reactive than
benzene), but they direct ortho-
and para- since they enhance
the electron density at these positions by resonance, as shown below.
When there are multiple
substituents on a ring, the effects are generally either cumulative, or the
most strongly activating substituent ultimately directs the regiochemistry.