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AROMATIC & HETEROCYCLIC CHEMISTRY
Aromatic Chemistry
Aromaticity
This confers an energetic stability over the equivalent double bond system. This can be
explained from an MO point of view. The Huckel Rule states that planar monocyclic
conjugated hydrocarbons are aromatic when the ring contains (4n+2)π electrons.
Huckel MO Theory (HMO) is used for conjugated planar molecules, both cyclic and
acyclic. It is based on the approximation that the σ framework does not interact with the
π-orbitals (orthogonal), and it can be used to calculate relative energies of MOs.
Aromaticity –
• Planar, fully conjugated, cyclic polyenes.
• Generally more stable than their acyclic analogues.
• As the number of π electrons increases, generally get more reactive.
• Bonds normally of nearly the same length.
• In a magnetic field, a ring current is set up (observable by NMR).
• Ability to undergo electrophilic substitutions.
Electrophilic Substitution
Evidence for this mechanism lies in the isolation of intermediates, and also kinetic
isotope effects (Step 1 is usually rate determining).
Nitration – HNO3 + 2H2SO4 forms NO2+.
Sulphonation – H2SO4 forms SO3 at 80oC.
Halogenation – X2 + Lewis Acid.
Alkylation and Acylation – Friedel-Crafts Reaction. Alkyl/Acyl Chloride + AlCl3.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -2-
Note that alkylation typically runs to completion by substituting three times, whereas
acylation shows less tendency to do this.
Formylation can be effected by adding HCl and CO with catalytic AlCl3. Other methods
include:
Vilsmeier Reaction
Hoesch Synthesis
Regiochemistry
From a purely statistical point of view we might expect the ratio of ortho:meta:para
products to be 2:2:1 based on the number of available sites. However, the nature of the
substituent group has a major effect on the ratio of products.
Electron-withdrawal by a halide (Inductive Effect, -I) has a slight effect, but it diminishes
rapidly with distance, and is typically outweighed by mesomeric (resonance) effects. The
same is true for electron-donation (slight with alkyls).
Mesomeric effects can be electron donating or electron withdrawing as well.
We see that for electron withdrawing groups, this favours meta.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -3-
A positive charge is placed next to the ortho and para positions, so the internal energies
for these intermediates will be higher (i.e. the reaction profile has higher energy
transition states) than that of the meta, and they are formed more slowly.
In contrast, mesomerically donating groups share the positive charge at the ortho and
para positions more effectively than at the meta, so their energy profiles are lower in
energy than for the meta, and so favoured.
Ipso Substitution
Summary of Substituent Effects
For EDG – generally ortho/para directing. All activated wrt benzene.
For EWG – meta directing. Deactivating wrt benzene.
Steric Factors
All things being equal, a third group is least likely to enter between two meta groups.
Ortho Rule: when an m-directing group is meta to an o/p-directing group, then
electrophile goes ortho to the m-directing group rather than para.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
AROMATIC & HETEROCYCLIC CHEMISTRY
Aromatic Chemistry
Aromaticity
This confers an energetic stability over the equivalent double bond system. This can be
explained from an MO point of view. The Huckel Rule states that planar monocyclic
conjugated hydrocarbons are aromatic when the ring contains (4n+2)π electrons.
Huckel MO Theory (HMO) is used for conjugated planar molecules, both cyclic and
acyclic. It is based on the approximation that the σ framework does not interact with the
π-orbitals (orthogonal), and it can be used to calculate relative energies of MOs.
Aromaticity –
• Planar, fully conjugated, cyclic polyenes.
• Generally more stable than their acyclic analogues.
• As the number of π electrons increases, generally get more reactive.
• Bonds normally of nearly the same length.
• In a magnetic field, a ring current is set up (observable by NMR).
• Ability to undergo electrophilic substitutions.
Electrophilic Substitution
Evidence for this mechanism lies in the isolation of intermediates, and also kinetic
isotope effects (Step 1 is usually rate determining).
Nitration – HNO3 + 2H2SO4 forms NO2+.
Sulphonation – H2SO4 forms SO3 at 80oC.
Halogenation – X2 + Lewis Acid.
Alkylation and Acylation – Friedel-Crafts Reaction. Alkyl/Acyl Chloride + AlCl3.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -2-
Note that alkylation typically runs to completion by substituting three times, whereas
acylation shows less tendency to do this.
Formylation can be effected by adding HCl and CO with catalytic AlCl3. Other methods
include:
Vilsmeier Reaction
Hoesch Synthesis
Regiochemistry
From a purely statistical point of view we might expect the ratio of ortho:meta:para
products to be 2:2:1 based on the number of available sites. However, the nature of the
substituent group has a major effect on the ratio of products.
Electron-withdrawal by a halide (Inductive Effect, -I) has a slight effect, but it diminishes
rapidly with distance, and is typically outweighed by mesomeric (resonance) effects. The
same is true for electron-donation (slight with alkyls).
Mesomeric effects can be electron donating or electron withdrawing as well.
We see that for electron withdrawing groups, this favours meta.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -3-
A positive charge is placed next to the ortho and para positions, so the internal energies
for these intermediates will be higher (i.e. the reaction profile has higher energy
transition states) than that of the meta, and they are formed more slowly.
In contrast, mesomerically donating groups share the positive charge at the ortho and
para positions more effectively than at the meta, so their energy profiles are lower in
energy than for the meta, and so favoured.
Ipso Substitution
Summary of Substituent Effects
For EDG – generally ortho/para directing. All activated wrt benzene.
For EWG – meta directing. Deactivating wrt benzene.
Steric Factors
All things being equal, a third group is least likely to enter between two meta groups.
Ortho Rule: when an m-directing group is meta to an o/p-directing group, then
electrophile goes ortho to the m-directing group rather than para.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
