1. Reactions of Arenes 1

2. Reactions of Arenes
Reactions involving the ring
A. Reduction
a. Catalytic hydrogenation (Chapter 11.4)
b. Birch reduction (Chapter 11.11)
B. Electrophilic aromatic substitution (Chapter 12)
C. Nucleophilic aromatic substitution (Chapter 23)
The ring as a substituent
A. Benzylic halogenation (Chapter 11.12)
B. Benzylic oxidation (Chapter 11.13)
C. Nucleophilic substitution of benzylic halides

3. Catalytic Hydrogenation - Aromatic rings are inert to catalytic
The Birch Reduction
Catalytic Hydrogenation - Aromatic rings are inert to catalytic
hydrogenation under conditions that will reduce alkene double
bonds. Therefore, an alkene double bond can therefore be
selectively reduced in the presence of an aromatic ring
Reduction of an aromatic ring requires forcing reducing
conditions (high pressure and/or highly active catalysts) 3

4. Birch Reduction – dissolving metal reduction of an aromatic ring
Li, Na or K metal in liquid ammonia.
Mechanism is related to the reduction of CC to
trans-alkenes 4

5. 11.12: Free-Radical Halogenation of Alkylbenzenes
The benzylic position (the carbon next to a benzene ring) is
analogous to the allylic position and can stabilize carbocations,
radicals, and anions.
380 kJ/mol •
(CH3)3C
(CH3)3C—H + H•
368 kJ/mol •
CHCH2—H
H2C
CHCH2
H2C + H•
356 kJ/mol •
C6H5CH2—H
C6H5CH2 + H• 5

6. Mechanism is the same as allylic bromination

7. Oxidation of Alkylbenzenes - Benzene rings do not
react with strong oxidants. However, the benzene ring can
activate the benzylic position of alkylbenzene toward oxidation
with strong oxidants such as KMnO4 and Na2Cr2O7 to give
benzoic acids.
Benzoic acid

8. SN1 Reactions of Benzylic Halides
> 600 times
more reactive
Reactivity is reflective of the greater stability of the benzylic
carbocation intermediate

9. SN2 Reactions of Benzylic Halides -
Benzylic halides undergo SN2 reactions faster than a alkyl
halides (similar to allylic halides)
Preparation of Alkenylbenzenes (please read)

10. Addition Reactions of Alkenylbenzenes - alkenyl
substituents on a benzene ring undergo reactions typical of an
alkene. The benzene ring can influence the reactivity.

11. Polymerization of Styrene (please read)
Cyclobutadiene and Cyclooctatetraene
Not all cyclic conjugated systems are aromatic (no special
stability)
Cyclobutadiene: highly reactive
two different C-C bonds

12. Cyclooctatetraene:
Heats of hydrogenation - No special stability for cyclooctatetraene
reactivity similar to normal C=C
Exists in a boat-like conformation:
little overlap between double bonds

13. Cyclic conjugation is necessary, but not sufficient criteria for
aromaticity.
Hückel's Rule:
Aromatic:
Cyclic
Conjugated: “alternating single and double bonds”
Planar: maximum overlap between conjugated  -bonds
Must contain 4n+2 -electrons, where n is an integer
(Hückel’s rule)
Anti-aromatic:
cyclic, conjugated, planar molecules that contain
4n -electrons (where n is an integer).
Destabilized (highly reactive) relative to the
corresponding open-chain conjugated system

14. Frost Circles: relative energies of the molecular orbitals of
cyclic, conjugated systems
Inscribe the cyclic, conjugated molecule into a circle so that a
vertex is at the bottom. The relative energies of the
MO’s are where the ring atoms intersect the circle
benzene:
The bonding MO's will be filled for aromatic compounds, such
as benzene.

15. Cyclobutadiene:
For anti- aromatic compounds, such as cyclobutadiene and
cyclooctatetraene, there will be unpaired electrons in bonding,
non-bonding or antibonding MO's.
Cyclooctatetraene:

16. 11.21: Annulenes - monocyclic, conjugated, planar polyenes
that conform to Hückel's rule.
[10]annulene
[14]annulene
[18]annulene
10 -electrons
4n+2 = 10, n=2.
14 -electrons
4n+2=14, n=3
18 -electrons
4n+2=18, n=4
[16]annulene
16 -electrons
4n=16, n=4

17. 11.22: Aromatic Ions

18. Cyclopropenyl cation
4n+2=2
n=0
aromatic
Cyclopentadienyl cation
4n=4
n=1
anti-aromatic
Cycloheptatrienyl cation
4n+2=6
n=1
aromatic

19. Cyclopropenyl anion
4n=4
n=1
anti-aromatic
Cyclopentadienyl anion
4n+2=6
n=1
aromatic

20. 11.23: Heterocyclic Aromatic Compounds (please read)
Heterocycle: any cyclic compound that contains ring atom(s)
other than carbon (N, O, S, P). Cyclic compounds that contain
only carbon are called carbocycles
11.24: Heterocyclic Aromatic Compounds and Hückel's Rule
Pyridine: -electron structure resembles benzene (6 -electrons)
The nitrogen lone pair electrons are not part of the aromatic
system.
pyridine

21. Pyrrole: 6 -electron system similar to that of cyclopentadienyl
anion. There are four sp2-hybridized carbons with 4 p orbitals
perpendicular to the ring and 4 -electrons and a lone pair of
electrons in an unhybridized p2 orbital that is part of the
aromatic sextet

22. Electrophilic Aromatic Substitution
Background
The characteristic reaction of benzene is electrophilic aromatic substitution—a hydrogen atom is replaced by an electrophile.

23. Benzene does not undergo addition reactions like other unsaturated hydrocarbons, because addition would yield a product that is not aromatic.
Substitution of a hydrogen keeps the aromatic ring intact.
There are five main examples of electrophilic aromatic substitution.

25. Regardless of the electrophile used, all electrophilic aromatic substitution reactions occur by the same two-step mechanism—addition of the electrophile E+ to form a resonance-stabilized carbocation, followed by deprotonation with base, as shown below:

26. The first step in electrophilic aromatic substitution forms a carbocation, for which three resonance structures can be drawn. To help keep track of the location of the positive charge:

27. The energy changes in electrophilic aromatic substitution are shown below:

28. Friedel-Crafts alkylation (variations)
Ar-H R-X, AlCl3  Ar-R HX
Ar-H R-OH, H+  Ar-R H2O
c) Ar-H Alkene, H+  Ar-R

30. toluene
faster than the same reactions with benzene

31. nitrobenzene
slower than the same reactions with benzene

32. Substituent groups on a benzene ring affect electrophilic aromatic substitution reactions in two ways:
reactivity
activate (faster than benzene)
or deactivate (slower than benzene)
orientation
ortho- + para- direction
or meta- direction

33. -CH3
activates the benzene ring towards EAS
directs substitution to the ortho- & para- positions
-NO2
deactivates the benzene ring towards EAS
directs substitution to the meta- position

34. Common substituent groups and their effect on EAS:
-NH2, -NHR, -NR2
-OH
-OR
-NHCOCH3
-C6H5 -R -H -X
-CHO, -COR
-SO3H
-COOH, -COOR
-CN
-NR3+
-NO2
ortho/para directors
increasing reactivity
meta directors

36. If there is more than one group on the benzene ring:
The group that is more activating (higher on “the list”) will direct the next substitution.
You will get little or no substitution between groups that are meta- to each other.

38. Orientation and synthesis. Order is important!
synthesis of m-bromonitrobenzene from benzene:
synthesis of p-bromonitrobenzene from benzene:
You may assume that you can separate a pure para- isomer from an ortho-/para- mixture.

39. note: the assumption that you can separate a pure para isomer from an ortho/para mixture does not apply to any other mixtures.

40. synthesis of benzoic acids by oxidation of –CH3

41. nitration +
HO-NO H2SO4  H2O-NO HSO4-
H2O-NO2  H2O NO2
H2SO H2O  HSO H3O+
HNO H2SO4  H3O HSO NO2+

42. nitration:
electrophile

43. resonance

44. Mechanism for nitration:

45. Mechanism for sulfonation:

46. Mechanism for halogenation:

47. Mechanism for Friedel-Crafts alkylation:

48. Mechanism for Friedel-Crafts with an alcohol & acid

49. Mechanism for Friedel-Crafts with alkene & acid:
electrophile in Friedel-Crafts alkylation = carbocation

50. “Generic” Electrophilic Aromatic Substitution mechanism:

51. Why do substituent groups on a benzene ring affect the reactivity and orientation in the way they do?
 electronic effects, “pushing” or “pulling” electrons by the substituent.
Electrons can be donated (“pushed”) or withdrawn (“pulled”) by atoms or groups of atoms via:
Induction – due to differences in electronegativities
Resonance – delocalization via resonance

54. X—

57. Common substituent groups and their effect on reactivity in EAS:
-NH2, -NHR, -NR2
-OH
-OR
-NHCOCH3 electron donating
-C6H5 -R -H -X
-CHO, -COR
-SO3H
-COOH, -COOR electron withdrawing
-CN
-NR3+
-NO2
increasing reactivity

58. Electron donating groups activate the benzene ring to electrophilic aromatic substitution.
electron donating groups increase the electron density in the ring and make it more reactive with electrophiles.
electron donation stabilizes the intermediate carbocation, lowers the Eact and increases the rate.

59. Electron withdrawing groups deactivate the benzene ring to electrophilic aromatic substitution.
electron withdrawing groups decrease the electron density in the ring and make it less reactive with electrophiles.
electron withdrawal destabilizes the intermediate carbocation, raising the Eact and slowing the rate.

64. If G is an electron donating group, these structures are especially stable.

66. Electron donating groups stabilize the intermediate carbocations for ortho- and para- in EAS more than for meta-. The Eact’s for ortho-/para- are lower and the rates are faster.
Electron donating groups direct ortho-/para- in EAS

67. If G is an electron withdrawing group, these structures are especially unstable.

69. Electron withdrawing groups destabilize the intermediate carbocations for ortho- and para- in EAS more than for meta-. The Eact’s for ortho-/para- are higher and the rates are slower.
Electron withdrawing groups direct meta- in EAS

70. Halogens are electron withdrawing but are ortho/para directing in EAS.
The halogen atom is unusual in that it is highly electronegative but also has unshared pairs of electrons that can be resonance donated to the carbocation.

72. Common substituent groups and their effect on EAS:
-NH2, -NHR, -NR2
-OH
-OR
-NHCOCH3
-C6H5 -R -H -X
-CHO, -COR
-SO3H
-COOH, -COOR
-CN
-NR3+
-NO2
ortho/para directors
increasing reactivity
meta directors