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: Br HBr
Reaction is faster than 1- Br HBr butene due to more stable Br carbocation intermediate Having conjugation in HBr ring somehow stabilizes No reaction compound
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
57.4 Kcal/mol Almost double in energy 55.4 Kcal/mol 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 Cyclobutadiene 6-fold symmetry 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
Nonbonded E 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
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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 4 π electrons, 4n No p orbital on one atom Therefore aromatic Therefore antiaromatic 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 All electrons Obtain 2 electrons at nonbonding level are at bonding level 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 Extremely low pKa is due to aromatic stabilization pKa ~15 nonaromatic
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 Unactivated alkanes have much higher pKa pKa ~50-60 base Simple conjugation only explains small portion of pKa ~44 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 Tropylium ion 6 π electrons, 4n+2
K 10 π electrons, 4n+2
Need correct number of conjugated electrons, not all conjugated ions are aromatic
OH
H2SO4 base
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- meta- para- dimethylbenzene dimethylbenzene dimethylbenzene Benzene Derivatives
Number along ring to give lowest number First priority substituent is at the 1-position
Other common names
O CH OH 3 OH
toluene 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 OH
Benzyl bromide Benzyl alcohol 4-phenyl-2-butanol 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 H N O S N N N NH pyridine pyrrole furan thiophene pyrimidine imidazole
All of these compounds have 6 electrons conjugated in ring Consider where the lone pair(s) are located for each heteroatom 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
Br HBr
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 O N N N NH
N N N N NH H H 2
Adenine (A) Guanine (G) 10 π electrons 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
O NH2 CH HN 3 N
O N O N H H Thymine (T) 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
O Hydrogen O Sugar O P O O P O N bonding N O O N G Sugar Base Base Sugar π stacking O O HN N O O P O O P O H H H O O O N NH Sugar Base Base Sugar O O N C Sugar O P O O P O O O
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 NH N N NH2 Sugar
O P450 P450
HO HO O 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 CH3ONa OCH3 SN2 Transition State
Br Cl
Cl I S 1 S 2 I N N I Intermediate: 2˚ cation 2˚ cation resonance T.S.: 1˚ 1˚ in resonance 1˚ in resonance Relative 1 100,000 Relative 1 33 78 rate: rate: 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 1. KMnO4 2. H+,H2O 2. H+,H2O O 1. KMnO4 1. KMnO4 CH3 2. H+,H2O OH 2. H+,H2O
1. KMnO 4 CO2H 2. H+,H2O
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 Na+
This electron is called a “solvated” electron 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 ROH
H H 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 X X NH3(l), Na ROH
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 O NH3(l), Na O CH3OH
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
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