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Ch 15 Reactions of Aromatic
Compounds
Intro
• Aromatic hydrocarbons are known generally
as arenes.
• An Aryl group is formed by the removal of a
hydrogen, and is symbolized with Ar• We have already talked about how stable the
double bonds are in arenes due to
conjugation.
• They resist typical addition reactions
Intro
• We have also said that the pi electrons form
clouds above and below the ring
• This makes nucleophilic attack very unlikely as
well
• The most characteristic reactions of arenes
are a new type of reaction called Electrophilic
Aromatic Substitution, (EAS)
EAS
• Generic reaction:
• The electrophiles in these reactions are either
a positive ion (E+) or some other electron
deficient species with a large partial positive
charge
EAS
• Mechanism:
• Aromaticity– Broken in 1st step- reactions usually require high
temps
– Regained in 2nd step- reason for substitution
instead of addition
• Arenium Ion- somewhat stabilized by
resonance; delocalized positive charge
Arenium ion
• Substituents already on the ring can effect the
stability of the arenium ion, and therefore effect the
reaction.
• Substituents on the ring are divided into 2
classification
• The first deals with how the substituents effect the
reactivity of the ring
• The second deals with how the substituents effect
the orientation of the incoming electrophile
Reactivity of the Ring
• Those substituents whose presence make the
ring more reactive than benzene are called
activating groups, or Activators
• Those that make the ring less reactive than
benzene are called De-activating groups, or
Deactivators
Reactivity of the Ring
• If we look at the energy diagram we see that
the 1st step is the RDS and that the Arenium
ion is a true intermediate, not a transition
state.
• By increasing the stability of the arenium ion,
we would be lowering it energy, therefore,
lowering the activation energy for the RDS,
making the reaction occur faster.
Reactivity of the Ring
• This is how Activating groups work
• They help to stabilize the Arenium Ion
• How can the Arenium Ion be stabilized?
Reactivity of the Ring
• Activating groups stabilize the arenium ion by
donating electrons into the cation.
• Strong Activators
• Moderate Activators
• Weak Activators
Reactivity of the Ring
• Deactivating groups have the opposite effect
• They decrease the stability of the arenium ion,
thereby increasing it energy, which increases the
activation energy for the reaction, making the
reaction occur slower.
• Note: Notice I said slower! The reaction will still
occur, just at a slower relative rate compared to
benzene.
Reactivity of the Ring
• Don’t think that just because a ring has a
deactivating group, that it won’t undergo a
reaction.
• For most reactions, it will still react just with a
slower relative rate.
• How would a group deactivate a ring?
Reactivity of the Ring
• Deactivators destabilize the arenium ion by
withdrawing electrons from the cation ion.
• Strong Deactivators
• Moderate Deactivators
• Weak Deactivators
Orientation
• The second classifications groups can be
divided into deals with the way they influence
the orientation of the incoming electrophile
• Some substituents tend to direct the
electrophiles to the ortho and para positions
relative to themselves; while others tend to
direct the electrophile to the meta positions.
Orientation
• To understand how these groups “direct” the
incoming electrophile, we again look at the
arenium ion.
• More specifically, we look at the resonance
structures of the arenium ion once the
electrophile adds to the ring.
Orientation
• Notice with both the ortho and para
positioning of the electrophile, the
carbocation can be shown on the carbon
directly bonded to the substituent
• With the meta positioning of the electrophile,
the carbocation never reaches the carbon
attached to the substituent.
Orientation
• Activators are electron donors, so their
stabilizing effects would be greater with the
carbocation directly bonded to them.
• Thus, all activators are ortho/para directors
• By contrast, deactivator are electron
withdrawing groups, so they want to avoid
being directly bonded to the carbocation
• Thus, strong and moderate deactivators are
meta directors
Exception
• Of course there is an exception!
• Halogens are weakly deactivating due to their
electronegativity, but ortho/para directors due
to an additional resonance structure.
Types of EAS Reactions
• All EAS reactions occur through the same,
basic mechanism.
• The only difference is the way the electrophile
is created/introduced
• Examples:
Halogenation of Benzene
• Benzene does not react with chlorine or
bromine unless a lewis acid catalyst is present
• Examples:
• Mechanism:
Nitration of Benzene
• Examples:
• Mechanism:
Sulfonation of Benzene
• General reaction:
• This reaction is an equilibrium
• We can influence the equilibrium by the
methods we use
• By using conc. H2SO4 or fuming H2SO4
(contains added SO3), the equilibrium is
pushed to the right, increasing the amount of
sulfonated benzene.
Sulfonation of Benzene
• By using dilute acid and steam, we can push
the equilibrium to the left, removing the
sulfonyl group.
• The steam helps remove the volatile aromatic
compound as it forms
• Mechanism:
Sulfonation of Benzene
• The control of this equilibrium is fairly simple
and is therefore very useful!
• Often, we may introduce a sulfonic acid group
to influence other reactions, then remove it
later.
• Example:
Friedal-Crafts Alkylation
• Discovered in 1877 as a new method of
making alkyl benzenes, (Ar—R)
• General Reaction:
• Mechanism:
Friedal-Crafts Alkylation
• Friedel-Craft alkylations are not restricted to alkyl
halides and aluminum chloride
• Many other pairs of reagents that form a
carbocation or species like carbocations, can be
used.
• Examples:
• There are several important limitations of FC
reactions.
• We will discuss these after the FC acylations
Friedal-Crafts Acylation
• The acyl group is basically half a ketone, it’s an
alkyl bonded to a carbonyl
• A reaction which introduces an acyl group is
an acylation
• There are two common acyl groups:
• The F.C. Acylation reaction is an effective
means of introducing an acyl group onto an
aromatic ring
Friedal-Crafts Acylation
• FC Acylations are often carried out using an
aromatic ring and an acyl chloride in the presence
of a lewis acid
• Examples
• The acyl chloride, aka acid chlorides, can be
prepared by adding thionyl chloride, SOCl2 or
phosphorus pentachloride, PCl5, to carboxylic acids
• Examples:
Friedal-Crafts Acylation
• FC acylations can also be carried out using
carboxylic acid anhydrides as the electrophile
• Example
• In most FC acylations, the electrophile is the
acylium ion
• Mechanism:
Limitations to FC Reactions
• As we said, there are several restrictions that
limit the usefulness of FC alkylations and
acylations
– 1) When the carbocation formed from the alkyl
halide, alkene, or alcohol can rearrange to a more
stable carbocation, it usually does so and the
major product obtained from the reaction is
usually the one from the more stable carbocation.
– Example:
Limitations to FC Reactions
• 2) Friedel-Crafts reactions usually give poor
yields when powerful electron withdrawing
groups are present on the aromatic ring or
when the ring bears an –NH2, -NHR, or –NR2
group.
• This includes all meta directing groups plus
the amine groups
• The deactivated rings are too electron
deficient to undergo a FC reaction
Limitations to FC Reactions
• As for the amines, they become deactivating
groups due to their reaction with the lewis
acid.
• Example
Limitations to FC Reactions
• 3) Aryl and vinylic halides cannot be used as the
halide component because they do not form
carbocations
• Examples
• 4) Polyalkylations often occur
– When putting activating groups on, in general, such as
alkyl groups, the product after the first addition is more
reactive than the starting material
– Example
– Polyacylations do not occur since the acyl group is a
deactivating group
Synthetic Applications
• Applications of the Friedel-Crafts Acylation reaction
followed by the Clemmensen Reduction
• Acylations have the advantage of not rearranging
due to the resonance stabilized acylium ion.
• Since they do not rearrange, FC Acylations followed
by reductions provide a better way for producing
unbranched alkyl benzenes.
• Examples
Clemmenson Reduction
• A Clemmenson reduction is used to reduce
the ketone adjacent to the aromatic ring down
to the methylene group.
• Example
• The clemmenson reduction only reduces the
carbonyl adjacent to the aromatic ring!
• Example
Reactions of the Side Chain of Alkyl
Benzenes
• Compounds that have both aromatic and
aliphatic groups are also called arenes
• Toluene, ethyl benzene, and isopropylbenzene
are alkylbenzenes
• Phenylethene, commonly known as styrene, is
an example of an alkenylbenzene
• The aliphatic portion of these compounds is
commonly called the side chain
Benzylic Radicals and Cations
• The carbon directly attached to the aromatic
ring in a alkyl benzene is the benzylic carbon
• Hydrogen abstraction from this carbon creates
the benzyl radical
• Example
• Departure of a leaving group from the benzylic
position produces a benzylic carbocation
• example
Benzylic Radicals and Cations
• Both radicals and cations are conjugated
unsaturated systems and both are unusually
stable
• They have approximately the same stability as
the allylic radical and cation
• This can be show with resonance
• example
Halogenation of the Side Chain
• Reaction via benzylic Radicals
• Earlier we saw we could add bromine and chlorine
to the actual ring with a lewis acid present
• This is done by creating an electrophile out of the
bromine and/or chlorine
• We can add a bromine and/or chlorine to a benzylic
carbon by promoting radical conditions and not
using a lewis acid catalyst
• Examples:
• Mechanism:
Halogenation of the Side Chain
• Because of the stability of the benzylic radical,
it forms faster than other radicals, therefore,
halogenation at the benzylic site is always the
major product
• Example:
Alkenyl Benzenes
• Alkenyl benzenes that have their double
bonds conjugated with the benzene ring are
more stable than those that do not:
• This is proven by the acid catalyzed
dehydration reaction which is known to give
the most stable alkene:
Alkenyl Benzenes
• Although the conjugated double bond is more
stable, the same reactions are still seen:
– HBr addition in presence of peroxides:
– HBr addition with no peroxides:
Oxidation of the Side Chain
• Strong oxidizing agents oxidize the alkyl
groups of alkyl benzenes to benzoic acid using
potassium permanganate:
• Example
• The first step in this process is the abstraction
of a benzylic hydrogen! (meaning there has to
be one there!!)
Oxidation of the Side Chain
• In order for the oxidation to take place, there
must be a benzylic hydrogen or the benzylic
carbon must be unsaturated
• Examples:
Oxidation of the Benzene Ring
• Conversely, the benzene ring of alkylbenzenes
can be oxidized to the carboxylic acid by using
ozone followed by peroxide
• General reaction:
• Example:
• Note: Must watch for other functional groups
Synthetic Applications
• The substitution reaction of aromatic rings
and the reactions of side chains of alkyl and
alkenyl benzenes, when taken together, offer
us a powerful set of reactions for organic
synthesis with great regio-control
• Part of the skill is using these reactions is
deciding the order in which reactions should
be carried out
Examples
• Synthesize o-bromonitrobenzene from
benzene.
• Synthesize p-nitrobenzoic acid from benzene
Use of Protecting/Blocking Groups
• Very powerful activating groups such as amino
groups and hydroxyl groups cause the
benzene ring to be so reactive, that multiple
and/or undesirable reactions may take place
• These groups may also react with some of the
reagents, such as HNO3 and H2SO4
Use of Protecting/Blocking Groups
• Amino groups must be protected by either
adding acetyl chloride or acetic anhydride to
convert the amino group to an acetamido
group
• The acetamido group is only mildly activating
and can easily be removed with dilute acid
• examples
Use of Protecting/Blocking Groups
• Groups such as the –SO3H, which are easy to put on
and take off, are also used as blocking groups
• For example, say we wanted to make o-nitroaniline:
• Because of the size of the acetamido group, the
ortho sites are sterically hindered, so if we add the
nitro at this point, the major product would be
para.
Use of Protecting/Blocking Groups
• Instead, we add a sulfuric acid group, which
goes para, then the nitro which can only go
ortho to the acetamido group
• The sulfuric acid group can the be removed
along with the acetyl chloride group at the
same time.
Orientation in Disubstituted Benzenes
• When two different groups are present on a
benzene ring, the more powerful activating group
generally determines the outcome of the reaction
• Example
• Because all ortho/para directors are more activating
than meta directors, the ortho/para director
determines the orientation of the incoming group
• Example:
Orientation in Disubstituted Benzenes
• Sterics also play an important role
• Substitution does not occur between meta
substituents if another position is open and
directed
• example
Allylic and Benzylic Halides in
Nucleophilic Substitution Reactions
• Allylic and benzylc halides are classified in the same
way as other halides, just add the allylic or benzylic
• Tertiary allylic and benzylic halides still only undergo
Sn1 reactions due to the steric hinderance.
• The difference is with the primary allylic and
benzylic halides.
• Because they would form a very stabilized
carboncation, primary allylic and benzylic halides
may undergo Sn1 reactions
The Birch Reduction
• Benzene can be reduced to 1,4cyclohexadiene by using an alkali metal (Na, Li,
or K) in a mixture of liquid ammonia and an
alcohol
• Example:
• This reaction is the only example we will see
that combines ionic and radical steps in the
mechanism!
• Mechanism:
The Birch Reduction
• Substituent groups on the ring can affect the
reaction as well
• One very important example of the Birch
reduction includes: