Chapter 18 Reactions of
Aromatic molecules
•Benzene is aromatic: a cyclic conjugated
compound with 6  electrons
•Reactions of benzene lead to the retention
of the aromatic core
Types of Reactions
• Electrophilic substitution
• Diazonium chemistry
• Nucleophilic substitution
• Misc. modification of substituents
Electrophilic Substitution Reactions of
Benzene and Its Derivatives
Electrophilic Substitution versus addition
Arenium ion: Wheland intermediate
Also called sigma complex
Energy diagram comparison of electrophilic
substitution versus electrophilic addition
Is this kinetic or thermodynamic
control?
Electrophilic Bromination of Aromatic Rings
toluene
para-bromotoluene
ortho-bromotoluene
meta-bromonitrobenzene
Regiochemistry (ortho, para, meta) will depend on relative
stability of resonance structures for carbocation intermediates
Mechanism for Electrophilic Bromination of
Aromatic Rings
para carbocation
ortho carbocation
ortho carbocation
Electrophilic substitution of
Bromobenzene
Halogens are ortho para directors, but are still deactivating compared with benzene
Transformations of Aryl bromides
Aromatic Nitration
• The combination of nitric acid and sulfuric acid produces
NO2+ (nitronium ion)
• The reaction with benzene produces nitrobenzene
Gun solvent
Nitration of toluene: an electron rich
monomer
ortho & para Regioselectivity explained
Kinetics are more favorable for ortho and para isomers with electron donating
substitutent on benzene
Too corrosive for artillery shells
•High explosive: Shock wave
•Secondary explosive: requires primer (primary explosive) to
detonate
•Nitroaromatics are harmful: aplastic anemia and liver
toxicity
Reactions of nitroaromatics
• Nitro is deactivating (destabilizes the Wheland
intermediate & slows reactions).
• Reactions are 100,000 slower than with benzene
• Meta directing
More polynitration
mono-bromination
Reduction to anilines and azo compounds
Nucleophilic aromatic substitution
Meta selective: electron
withdrawing groups
•electron withdrawing group inductively destabilizes
adjacent carbocations in ortho and para cases.
• No adjacent carbocation in meta regiochemistry
resonance structures
Reduction of Nitroaromatics to Aryl amines
Amine group is electron donating: changes subsequent regiochemistry from meta to
ortho-para
Aromatic Sulfonation
•
•
•
•
Substitution of H by SO3 (sulfonation)
Reaction with a mixture of sulfuric acid and SO3
Reactive species is sulfur trioxide or its conjugate acid
Reaction occurs via Wheland intermediate and is
reversible
Alkali Fusion of Aromatic Sulfonic Acids
• Sulfonic acids are useful as intermediates
• Heating with NaOH at 300 ºC followed by neutralization
with acid replaces the SO3H group with an OH
• Example is the synthesis of p-cresol
Alkylation of Aromatic Rings: The Friedel–Crafts
Reaction
• Aromatic substitution of a R+ for H
• Aluminum chloride promotes the formation of
the carbocation
• Rearrangement of carbocation can occur
Friedel Craft alkylation mechanism
Friedel Craft alkylation with
rearrangements
Limitations of the Friedel-Crafts Alkylation
• Only alkyl halides can be used (F, Cl, I, Br)
• Aryl halides and vinylic halides do not react (their
carbocations are too hard to form)
• Will not work with rings containing an amino group
substituent or a strongly electron-withdrawing group
Control Problems
• Multiple alkylations can occur because the first alkylation
is activating
Acylation of Aromatic Rings
• Reaction of an acid chloride (RCOCl) and an aromatic ring
in the presence of AlCl3 introduces acyl group, COR
– Benzene with acetyl chloride yields acetophenone
Friedel Craft Acylation Mechanism
Acylation – No rearrangement of
acylium ions
Ortho- and Para-Directing Deactivators:
Halogens
• Electron-withdrawing inductive effect outweighs weaker
electron-donating resonance effect
• Resonance effect is only at the ortho and para positions,
stabilizing carbocation intermediate
Strongly Activating o,p directors: Multiple additions
Reduce reactivity with acetyl groups
Summary of activation versus deactivation
and ortho & para versus meta direction
With multiple substitutents there can
be antagonistic or reinforcing effects
Antagonistic or Non-Cooperative
Reinforcing or Cooperative
D = Electron Donating Group (ortho/para-directing)
W = Electron Withdrawing Group (meta-directing)
Multiple Substituents in
antagonistic systems
The most strongly activating substituent will
determine the position of the next
substitution. May have mixtures.
O C H3
O C H3
S O 3H
SO 3
O 2N
H2S O 4
O C H3
+
O 2N
O 2N
S O 3H
=>
Sulfonic acid blocking groups
?
?
Electrophilic substitution reaction used
to make plastics
Acid or base catalyzed reactions
Acid catalyzed reaction of phenol with formaldehyde
Bakelite, Novolac
Electrophilic substitution reaction used
to make plastics
Acid catalyzed reaction of phenol with formaldehyde
Electrophilic substitution reaction used
to make plastics
Base catalyzed reaction of phenol with formaldehyde
Nucleophilic Aromatic Substitution
• While protons attached to electron-rich aromatics can be
displaced by electrophiles, halogens attached to electrondepleted aromatics can be displaced by nucleophies
• Nucleophilic aromatic substitution is similar to SN1/SN2 in its
outcome, but follows completely different mechanisms
Substitution Nucleophilic Aromatic (SNAr), the Benzyne Mech,
and reaction of diazonium salts
SNAr Mechanism: Electron EWG’s
Addition-Elimination Reactions
• Typical for aryl halides
with nitro groups in
ortho or para position
• Addition to form
intermediates
(Meisenheimer
complexes) by electronwithdrawal
• Halide ion is then lost by
elimination
Chlorobenzene is unreactive under
ordinary laboratory conditions…
…but brute force will do the job!
However, this can’t be the same mechanism
Nucleophilic substitution aromatic
Strong EWG ortho or para to leaving group (F, Cl, Br, I, OTf)
Strong nucleophile (HO-, RO-, Amide, thiolate, carbanions)
SNAr used in making polymers (plastics)
Elimination-Addition: Benzynes
• The reaction involves an elimination reaction that gives a
triple bond, followed by rapid addition of water
• The intermediate is called benzyne
Evidence for Benzyne as an Intermediate
• Bromobenzene with 14C only at C1 gives substitution
product with label scrambled between C1 and C2
• Reaction proceeds through a symmetrical intermediate in
which C1 and C2 are equivalent— must be benzyne
Structure of Benzyne
• Benzyne is a highly distorted alkyne
• The triple bond uses sp2-hybridized carbons, not the usual
sp
• The triple bond has one  bond formed by p–p overlap
and by weak sp2–sp2 overlap
Another Nucleophilic Like reaction using
Diazonium Salts (made from Anilines)
ArNH2 is easily made from reduction of nitrobenzenes. Permits preparation of molecules
impossible to make otherwise
Mechanism for formation of Diazonium Salts
from Anilines
Three possible reaction mechanisms for
Nucleophilic substitution reactions with
Diazonium salts
Thermal ionization (like SN1)
e.g. Formation of phenol
Redox (radical intermediate)
Organometallic
e.g. Sandmeyer reaction
Diazonium chemistry
62
16.10 Oxidation of Aromatic Compounds
• Alkyl side chains can be oxidized to CO2H by strong
reagents such as KMnO4 and Na2Cr2O7 if they have a C-H
next to the ring
• Converts an alkylbenzene into a benzoic acid, ArR 
ArCO2H
Bromination of Alkylbenzene Side Chains
• Reaction of an alkylbenzene with N-bromo-succinimide
(NBS) and benzoyl peroxide (radical initiator) introduces Br
into the side chain
Mechanism of NBS (Radical) Reaction
• Abstraction of a benzylic hydrogen atom generates an
intermediate benzylic radical
• Reacts with Br2 to yield product
• Br· radical cycles back into reaction to carry chain
• Br2 produced from reaction of HBr with NBS
16.11 Reduction of Aromatic Compounds
• Aromatic rings are inert to catalytic hydrogenation under
conditions that reduce alkene double bonds
• Can selectively reduce an alkene double bond in the
presence of an aromatic ring
• Reduction of an aromatic ring requires more powerful
reducing conditions (high pressure or rhodium catalysts)
Summary of reactions not involving aromatic
substitution
• Reduction of nitrobenzenes to anilines
• Conversion of benzenesulfonic acids to phenols
• Side chain oxidation of alkylbenzenes to benzoic
acids
• Side chain halogenation of alkylbenzenes
• Reduction of benzenes to cyclohexanes
• Reduction of aryl ketones to alkyl benzenes