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Benzene is different

Benzene benefits from aromatic resonance energy


Sharing of 6 electrons in a cyclic system leads to structural changes
Benzene has different chemistry than alkenes

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Experimental aromatic resonance energy

Heat of hydrogenation data can be used to compare stabilities of systems.

Conjugation in cyclohexadiene is worth ca. 3 kcal/mol of stabilization

Adding another double bond and forming a cyclic system is worth about 29
kcal/mol = aromatic resonance energy
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Not all rings are created equal

+56 kcal
28 kcal

PM A-res-E = 28 kcal/mol A-res-E = 56 kcal/mol 3


The Frost circles

Frost circles are a mnemonic for identifying MOs of mono-cyclic aromatic systems.

Draw the regular polygon standing on its corner within a circle:


vertices represent -MOs energies, with center of the circle serving as
reference energy (E = 0).

In benzene all -MOs are bonding; there are no unpaired electrons.


In cyclobutadiene the HOMO is nonbonding, and there are unpaired electrons.

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Cyclopropenyl system

Cyclopropenyl cations are so stable (A-res-E +25 kcal/mol) that some could be kept in a
bottle, and with some substituents (like 1,2,3-tri-t-butylcyclpropenyl cation) they may be
crystallized from water (i.e. the carbocation is more stable than the alcohol).

Cyclopropenyl anion is so unstable (A-res-E 21 kcal/mol) that it has never been directly
observed (despite numerous attempts).

2 electrons => stable = aromatic 4 electrons => unstable (diradical) = antiaromatic


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Cyclobutadiene

1,3-Cyclobutadiene is destabilized (A-res-E 56 kcal/mol). It minimizes the destabilization


by distortions of its geometry from square to rectangular, with rapid interconversion of the
two rectangular structures (alternating bonds).

It is very reactive; if there are no other reagents, it reacts with itself.

4 electrons => unstable = antiaromatic (avoids being a diradical by geometry distortions)


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Cyclopentadienyl system

The cyclopentadienyl anion is aromatic. The stability (A-res-E +20 kcal/mol) of the anion is
reflected in the pKa of the hydrocarbon. Cyclopentadiene is as acidic as water (pKa= 16).

Cyclopentadienyl cation is antiaromatic (A-res-E 50 kcal/mol). It can only be observed at


very low temperatures. It has two unpaired electrons.

6 electrons => stable = aromatic 4 electrons => unstable (diradical) = antiaromatic

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Cycloheptatrienyl system

The cation is aromatic, stable and its salts can be kept in a bottle. It forms easily
when cycloheptatriene reacts with Br2.

The anion is antiaromatic, it can only be observed at low temperature and it is very reactive.

6 electrons => stable = aromatic 8 electrons => unstable (diradical) = antiaromatic

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Applications of substitution: ethers

To avoid being antiaromatic, cyclooctatetraene takes its bonds


out of conjugation, by bending into a tub shape, with alternating
single and double bonds. It behaves as normal polyene; i.e. it is
non-aromatic. The planar version is estimated to have
A-res-E 33 kcal/mol and is less stable than the tub by about
15 kcal/mol.

8 electrons => unstable (diradical) = antiaromatic

Two electrons can be added to cyclooctatetraene


to give aromatic dianion that is stable in solution.
10 electrons => stable = aromatic
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Hckel rule

Based on the analysis of the electron occupancy:

(4n + 2) e = extra stable: aromatic (4n) e = extra unstable: antiaromatic

The rule strictly applies to mono-cyclic systems, but if applied carefully, it also
covers polycyclic systems.

In general molecules can be divided into:

1. aromatic (extra stabilized): molecules with planar (or nearly planar), cyclic systems
with (4n+2) electrons
2. antiaromatic (extra destabilized): molecules with planar (or nearly planar), cyclic
systems with (4n) electrons
3. non-aromatic: neither of the above category

All molecules that can be aromatic will be aromatic.


All molecules that can avoid being antiaromatic will do so by geometric distortions.

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Aromatic heterocycles

Ar-res-E (kcal/mol)
(benzene 36 kcal/mol)

Location of lone pars: which pairs participate in aromatic system

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Larger rings and polycyclic aromatics

If criteria for aromaticity are met. Many unusual structures can exhibit aromatic stabilization.

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Aromaticity and structure

Formally non-aromatic structures (odd number of electrons in the ring) have


resonance contributors than can help to stabilize the compound if they are aromatic,
PM or destabilize it if they are antiaromatic. 13
Aromaticity and structure

Diminished double bond character

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Aromatic electrophilic substitutions

Benzene is less nucleophilic than alkene


(lower HOMO).

In the slow step addition of electrophile


gives a carbocation intermediate.

In the second (fast) step proton is lost


(equivalent to E1).

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Substitution vs. addition

1. 1st step is rate limiting: destruction of aromatic stabilization even if the carbocation
is resonance stabilized).
2. Usually, E+ has to be more reactive (positively charged; i.e. more electron deficient)
than in electrophilic additions to alkenes.
3. A proton removal in the second step by X re-establishes aromatic stabilization (no
addition is observed). (E1 is faster than SN1)

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Preparing strong electrophiles

Strong electrophiles are prepared with the help of Lewis or Brnsted acids.
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Substitution: examples

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Nitration of toluene

the major products are


derived from the most stabilized
carbocations

Methyl group is activating and o/p-directing


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Nitration of anisole

Resonance effect dominate inductive effect (the same for O, N, S)


Methoxy group is activating and o/p-directing
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Nitration of benzaldehyde

The product is derived from the least-destabilized carbocation

Formyl group is deactivating and m-directing


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Nitration of chlorobenzene

For chlorine (and halogens in general) inductive effects dominate resonance effects.

Chlorine group is deactivating and o/p-directing

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Substituent effect

EWG EDG

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Substituent effect
(one H in benzene = 1)

Z any atom with a lone pair V and W are any atoms as long
as W is more electronegative than V
o-, p- directing (C=O, N=O, S=O, C=N, CN)

activating for O, N; S m- directing

deactivating for halogens deactivating

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Substituent effect: multiple substituents
sterics
directing effects directing effects in
in agreement disagreement;
EDG will dominate

directing effects
directing effects in disagreement;
In agreement; stronger EDG will
strong activation dominate

directing effects directing effects


in agreement; in disagreement;
strong deactivation strong deactivation

PM Aromatics with two strong EWG rarely participate in substitutions 25


Benzylic oxidations

Oxidation at benzylic positions:


strong oxidant (KMnO4) -> carboxylic acids (oxidative cleavage)
weaker oxidant (DDQ) > ketones; does not work if strong EWG
are present

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Aromatic ring hydrogenation

Aromatic rings can be reduces (hydrogenated) by Pd/H2 at very high pressures


(> 100 atm) or with H2/Rh at atmospheric or elevated pressures.

It is all or nothing process (no partial reduction is possible).

Diastereoselectivity is variable

Any reducible side group are also reduced (C=C, CC, C=O, NO2)
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Substituent reduction

Directly bonded (aromatic) nitro groups (-NO2) and carbonyl groups (-C=O) are easily
reduced (by hydrogenation or otherwise).

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Problems with Friedel-Crafts reactions

+ + +

The products are more reactive than the starting material => multiple alkylations
PM Further complications: carbocation rearrangements 29
Friedel-Crafts acylation

Friedel-Crafts acylation solve the over alkylation problem. The ketone is an EWG
group so no further acylation takes place.

The aromatic ketone can be reduced to methylene group (=> product of alkylations).

Limitation: Friedel-Crafts reactions (acylations and especially alkylations) do


not work for rings with strong EWG group.

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Phenol synthesis

Oxygen electrophiles for aromatic substitution are not know; indirect methods is used.

The sulfonylation is carried out first, followed by fusion with NaOH.

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Aromatic synthesis: substituents

Retrosynthetic analysis: careful sequencing of electrophile-substitution steps to


PM have the correct directing effects of groups introduced in earlier steps. 32
Aromatic synthesis: substituents

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