Aromatic Compounds
Early in the history of organic chemistry (late 18th, early 19th century) chemists discovered a class of compounds which were unusually stable
A number of these compounds had a distinct odor
Hence these compounds were called “aromatic”
Today the term aromatic is used regardless of the odor of the compound
Some “aromatic” compounds have little to no odor
The parent aromatic compound was discovered
to have a molecular formula of C6H6
(called benzene)
This 1:1 ratio of carbon to hydrogen is extremely low compared to other known compounds
It was also quickly discovered that these aromatic compounds did not react like other alkene compounds
Structure of Benzene
Before NMR and other spectroscopic tools it was hard to determine the structure of organic compounds
Ultimately the symmetry of the molecule revealed its structure
All carbon atoms, and all carbon-carbon bonds, are symmetrically equivalent
To account for these observations the proposed structure consisted of a cyclic compound stabilized by resonance
Each resonance structure is equal in energy and thus each contributes equally to the overall structure
Stability
The resonance structures imply an extra stability, but the amount of stability in benzene is much more than a typical resonance structure
Consider reactivity:
HBr
Reaction is faster than 1butene due to more stable
carbocation intermediate
Having conjugation in
ring somehow stabilizes
compound
HBr
Br
Br
Br
HBr
No reaction
But the presence of a conjugated ring is not enough to cause this extra stability
HBr
Br
What causes this extra stability in benzene and why is a 6-membered conjugated ring more stable than an 8-membered conjugated ring?
Stability of Aromatic Compounds
Can measure stability by hydrogenation
H2
catalyst
The energy required for this hydrogenation indicates the stability of the alkene
2 Kcal/mol
Conjugation stability
55.4 Kcal/mol
57.4 Kcal/mol
Almost double in energy
49.8 Kcal/mol
? Kcal/mol
28.6 Kcal/mol
How much energy should be in the hydrogenation of Benzene?
Have three double bonds in conjugation, so therefore should expect ~79 Kcal/mol
(~24 Kcal/mol more than 55 Kcal/mol for 1,3-cyclohexadiene)
Benzene is ~ 30 Kcal/mol more stable than predicted!!
Aromatic Stabilization
This ~30 Kcal/mol stabilization is called “aromatic stabilization”
It is the cause of the difference in reactivity between normal alkenes
It would cost ~30 Kcal/mol to break the aromaticity and thus the normal alkene reactions do not occur with benzene
Somehow having these three double bonds in resonance in a cyclic system offers a tremendous amount of energy
Aromatic Stabilization
Cyclic system alone, however, is not sufficient for aromatic stabilization
Consider a four membered ring
Cyclobutadiene also has a ring structure with conjugated double bonds that could resonate
This compound however is highly reactive and does not exist with equivalent single and double bonds
In solution it reacts with itself in a Diels-Alder reaction
Aromatic Stabilization
Why the Difference in Stability?
Can already see in electron density maps that cyclobutadiene is not symmetric
Benzene
6-fold symmetry
Cyclobutadiene
Not symmetric
Molecular Orbitals for Benzene
For benzene there are 6 atomic p orbitals in conjugation, therefore there will be 6 MO’s
-As the number of nodes increase, the energy increases
For lowest energy MO there are zero nodes, therefore bonding interactions between each carbon-carbon bond
Benzene model
Top view with orbitals
Side view
Entire MO Picture for Benzene
6 nodes
4 nodes
4 nodes
E
Nonbonded energy level
2 nodes
2 nodes
Zero nodes
Molecular Orbitals for Benzene
Notice all electrons are in bonding MO’s
All the antibonding MO’s are unfilled
With a cyclic system we obtain degenerate orbitals
(orbitals of the same energy)
Overall this electronic configuration is much more stable than the open chain analog
>
This is now the definition of an aromatic compound (not aroma),
Flat conjugated cyclic system is MORE stable than the open chain analog
Molecular Orbitals for Cyclobutadiene
E
Nonbonded energy level
Unlike benzene, cyclobutadiene has two electrons at the nonbonding energy level
(these electrons do not stabilize the electronic structure)
Antiaromatic
Cyclobutadiene is less stable than butadiene
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If a cyclic conjugated system is less stable than the open chain analog
it is called antiaromatic
Part of the reason for cycobutadiene to be antiaromatic
is the presence of two MO’s at the nonbonding level
In butadiene all electrons are in bonding MO’s therefore the electrons are more stable in butadiene relative to cyclobutadiene
Frost Circle
A simple method to determine the relative molecular orbital energy levels for a conjugated ring is called a Frost circle (or Frost Mnemonic)
First just draw a circle
Next draw a polygon with equal length of sides corresponding to the number of atoms in the ring being considered Place the polygon inside the ring having a vertex point directly at the bottom
Wherever a vertex point of the polygon hits the ring corresponds to an energy level
The electronic configuration would be obtained by placing the correct number of electrons in the molecular orbitals
(the relative energy levels are also obtained as the ring drawn initially has a radius of 2β)
Will work for any flat, conjugated ring system to determine energy levels
Hückel’s Rule
In order to determine if a system is aromatic or antiaromatic, without needing to determine the overall electronic energy of the closed form versus the open form, Hückel’s rule was developed
First the cyclic system must have a p orbital on all atoms in a continuous cyclic chain
(if there is an atom without a p orbital in the cycle then the system is nonaromatic)
In practice this means the cyclic system must be flat
(to allow overlap of p orbitals)
If these criteria are met then:
If the system has 4n+2 π electrons, it is aromatic
If the system has 4n π electrons, it is antiaromatic
6 π electrons, 4n+2
Therefore aromatic
4 π electrons, 4n
Therefore antiaromatic
No p orbital on one atom
Therefore nonaromatic
Hückel’s Rule
What is the underlying cause for the symmetry in Hückel’s rule?
Ultimately the stabilization is due to the relative electronic configuration for a flat,
conjugated ring system
The symmetry is also observed with the Frost circle
4 π electron system
6 π electron system
8 π electron system
Obtain 2 electrons at
nonbonding level
All electrons are at bonding level
Obtain 2 electrons at
nonbonding level
4n+2 systems allow all electrons to be in bonding molecular orbitals, therefore more stable
4n systems, however, will place 2 electrons at nonbonding level and thus be less stable
Hückel’s Rule
Remember that the cyclic ring must have overlap of p orbitals to be considered aromatic or antiaromatic by Hückel’s rule
Cyclooctatetraene
If flat this molecule is antiaromatic with the 8 π electrons
Molecule, however, adopts a non-flat low energy conformation top view
side view
This is an example of a rare case where delocalization is avoided to increase stability!
Aromatic Ions
Benzene is a neutral aromatic compound
Any compound with 4n+2 electrons in a continuous loop is considered aromatic regardless of the number of carbons in the loop
There are many aromatic compounds with a different number of electrons than atoms in the loop
Due to this difference usually these compounds are ions, hence aromatic ions
Cyclopentadienyl Anion
Cyclopentadiene is nonaromatic since there is not a p orbital on one of the carbons in the ring
base
nonaromatic
pKa ~15
Extremely low pKa is due to
aromatic stabilization
H
H
Upon removal of a proton, however, there is now a p orbital on each carbon
6 electrons in system, therefore according to Hückel this is aromatic
base
pKa ~50-60
base
pKa ~44
Unactivated alkanes have
much higher pKa
Simple conjugation only
explains small portion of
stability
Aromatic Ions
Any compound that will have 4n+2 electrons in a continuous loop
for planar conjugated compound will be favored due to aromatic nature
OH
H2SO4
K
Tropylium ion
6 π electrons, 4n+2
10 π electrons, 4n+2
Need correct number of conjugated electrons, not all conjugated ions are aromatic
OH
base
H2SO4
Does not form!
High pKa
Benzene Derivatives
The IUPAC name of 1,3,5-cyclohexatriene is never used
The common name of benzene dominates naming of these structures
In addition, another common naming tool for benzene derivatives
is for disubstituted compounds (ortho, meta, para)
ortho-
dimethylbenzene
meta-
dimethylbenzene
para-
dimethylbenzene
Benzene Derivatives
Number along ring to give lowest number
First priority substituent is at the 1-position
Other common names
O
CH3
toluene
OH
OH
phenol
benzoic acid
If benzene group is being considered as a Another common name used for a substituted
substituent, instead of root name, then use
toluene is called “benzyl” group
“phenyl” prefix, from phenol name
OH
Br
Benzyl bromide
4-phenyl-2-butanol
OH
Benzyl alcohol
Heterocyclic Aromatic Compounds
Compounds that contain atoms besides carbon can also be aromatic
Need to have a continuous loop of orbital overlap and follow Hückel’s rule for the number of electrons in conjugation
Common noncarbon atoms to see in aromatic compounds include oxygen, nitrogen, and sulfur
N
pyridine
H
N
pyrrole
O
S
furan
thiophene
N
N
pyrimidine
All of these compounds have 6 electrons conjugated in ring
Consider where the lone pair(s) are located for each heteroatom
N
NH
imidazole
Pyridine
One common aromatic compound with nitrogen is pyridine
N
One carbon atom of benzene has been replaced with nitrogen
Consider the placement of electrons
N
Lone pair is orthogonal to conjugated electrons in ring
The number of electrons in conjugation is 6
(don’t include lone pair that is orthogonal to ring)
therefore pyridine follows Hückel’s rule and is aromatic
Pyridine can be protonated in acidic conditions and it will still be aromatic, protonation occurs at lone pair
Pyrrole
A similar aromatic compound is pyrrole
H
N
N H
With pyrrole the lone pair is included in the conjugated ring
Have 6 electrons in loop and therefore this compound is aromatic
If protonated, however, pyrrole will become nonaromatic since the nitrogen would thus be sp3 hybridized without a p orbital for conjugation
Heterocyclic Aromatic Compounds
Difference in electron placement affects properties
pyridine
pyrrole
Excess electron density of lone pair is localized orthogonal to ring in pyridine while the electron density is conjugated in ring with pyrrole
Fused Rings
Compounds with more than one fused ring can also be aromatic
Naphthalene
The simplest two ring fused system is called naphthalene
Like benzene, naphthalene is an aromatic compound
with 10 electrons in a continuous ring around the cyclic system (one p orbital on each carbon is conjugated)
Consider one electron
Electron can resonate in p orbitals
Will occur with all 10 electrons
Fused Rings
The reactivity of naphthalene is similar to benzene
It is unreactive toward normal alkene reactions because any addition would lower the aromatic stabilization
If it did react, however, there would still be one benzene ring intact
HBr
Br
Hypothetical reaction – does not occur
With larger fused ring systems normal alkene reactions start to occur
Anthracene
Br
Br2
Br
Two intact benzene rings
Reactions occur at central ring due to large aromatic stabilization remaining
Two intact benzene rings
NO2
NO2
Diels-Alder reactions can also occur about this central ring
The dienophile approaches the central ring from top or bottom
And then Diels-Alder reaction occurs to leave two intact benzene rings
Fused Heterocyclics
Fused ring systems with heterocyclics can also be aromatic
Extremely important compounds biologically and medicinally
NH2
N
N
N
H
O
N
NH
N
H
N
Adenine (A)
10 π electrons
N
NH2
Guanine (G)
10 π electrons
Two of the four constituents of base pairs in DNA consist of fused aromatic rings, the other two bases, cytosine (C) and thymine (T), are one ring aromatic base pairs
NH2
O
CH3
HN
O
N
H
Thymine (T)
N
O
N
H
Cytosine (C)
Aromatic Base Pairing
The four bases shown in the preceding page (A, G, C, T) are the bases used in DNA
The bases are attached to a sugar through the NH group on each ring and the sugars are linked through a phosphate backbone
π stacking
O
Hydrogen O P O
bonding
O
O
Sugar Base Base
O
O P O
O
O
Sugar Base Base
O
O P O
O
O
O
P O
O
Sugar
O
P O
O
Sugar
O
P O
O
Sugar
N
N
N
HN
H
N
H
O
Sugar
G
N
O
H
NH
N
C
The bases are complementary to each other and bind through hydrogen bonding
(C binds with G and A binds with T)
This complementarity allows genetic information to be passed along as the DNA is replicated
Things that disrupt this complementarity can cause cell death or possibly cancer
Polycyclic Aromatic Hydrocarbons
Polycyclic aromatic hydrocarbons (PAH’s) have been shown to disrupt this base pairing
The PAH is first oxidized by enzymes (these enzymes are essential to remove hydrophobic compounds in the body)
O
N
N
Sugar
NH
N
NH2
O
P450
P450
O
HO
HO
OH
OH
Need PAH to react,
Benzene or naphthalene would
not undergo this reaction
Guanine can react with this epoxide, however, which will destroy its hydrogen-bonding
complementarity in the DNA base pairing, thus causing cells to eventually die
Benzyl Group
The benzyl group behaves similar to the allyl group seen previously, the orbitals on this group are stabilized through resonance with the adjacent benzene group
Cl
OCH3
CH3OH
SN1
Intermediate
NUC
I
SN2
CH3ONa
OCH3
Transition State
Br
Cl
SN1
Cl
Intermediate:
2˚ cation
2˚ cation resonance
Relative
rate:
1
I
SN2
100,000
I
I
T.S.:
1˚
Relative rate:
1
1˚ in resonance
1˚ in resonance
33
78
Benzyl Group
A unique reaction of benzyl groups is that the benzyl carbon can be oxidized with either
potassium permanganate (KMnO4) or dichromic acid (H2Cr2O7) to a carboxylic acid
1. KMnO4
2. H+,H2O
CH3
1. KMnO4
2. H+,H2O
1. KMnO4
2. H+,H2O
O
OH
1. KMnO4
2. H+,H2O
1. KMnO4
2. H+,H2O
CO2H
HO2C
If alkyl chain is longer, then carbon-carbon bonds are broken and left with benzoic acid
Must have hydrogen on benzylic carbon, though, as a t-butyl group will not be oxidized
Realize also this reaction is not selective, any alkyl chain on benzene will be oxidized
Benzyl Group
As seen in chapter 12, halogenation reactions can occur with either chlorine or bromine under photolytic conditions
Reaction proceeds through a radical intermediate
The benzylic radical is more stable due to resonance with aromatic ring
CH2
Remember that chlorination was more reactive, bromination though occurred selectively
Cl
Cl
Cl2, h!
Br
Br2, h!
Realize reaction does not occur on aromatic ring,
do not obtain radical at sp2 hybridized carbon
Birch Reduction
While typical alkene reactions do not occur on benzene, the aromatic ring can be reduced by adding electrons to the system (in essence a nucleophilic addition)
The reduction is similar to the dissolving metal reduction of alkynes to E-alkenes
The electrons need to be generated in situ
NH3(l)
Na
NH3(l)
e
This electron is called a “solvated” electron
Na+
Birch Reduction
In the presence of an aromatic ring this electron will react
e
Addition of one electron thus generates a radical anion
This strongly basic anion will abstract a proton from alcohol solution
ROH
H H
Birch Reduction
The radical will then undergo the same operation a second time
H H
e
H H
ROH
H H
H H
The final product has thus been reduced from benzene to a 1,4-cyclohexadiene
(always obtain a 1,4 relationship of the dienes in a Birch reduction – they are not conjugated)
The aromatic stabilization has been lost
Birch Reduction
What happens if there is a substituent on the aromatic ring before reduction?
X
NH3(l), Na
ROH
X
X
Which regioisomer will be obtained?
Similar to every other reaction studied need to ask yourself, “What is the stability of the intermediate structure?”
The preferred product is a result of the more stable intermediate
Birch Reduction
The intermediate in a Birch reduction is the radical anion formed after addition of electron
With electron withdrawing substituent:
O
O
NH3(l), Na
CH3OH
O
O
Placing negative charge adjacent to carbonyl allows resonance
With electron donating substituent:
NH3(l), Na
OCH3 CH3OH
OCH3
OCH3
Want negative charge as far removed from donating group as possible
Spectroscopy of Aromatic Compounds
We have already seen how aromatic benzene compounds have a relatively large downfield NMR shift due to aromatic ring current
Therefore any of these aromatic systems, which by definition have a ring current, have a large downfield shift
Can use as a characteristic of aromaticity
S
N
Mass Spectrometry
A characteristic peak in a MS for a benzenoid compound
is the presence of a peak at m/z 91 (if formation is possible)
Due to resonance stabilized benzyl cation