1. Electrophilic Aromatic Substitution
Electrophile substitutes for a hydrogen on the benzene ring.
=>
Chapter 17

2. Mechanism
=>
Chapter 17

3. Energy Diagram for Bromination
=>
Chapter 17

4. Bromination of Benzene
Requires a stronger electrophile than Br2.
Use a strong Lewis acid catalyst, FeBr3.
Chapter 17

5. Chlorination and Iodination
Chlorination is similar to bromination. Use AlCl3 as the Lewis acid catalyst.
Iodination requires an acidic oxidizing agent, like nitric acid, which oxidizes the iodine to an iodonium ion.
=>
Chapter 17

6. Nitration of Benzene
Use sulfuric acid with nitric acid to form the nitronium ion electrophile.
NO2+ then forms a
sigma complex with
benzene, loses H+ to
form nitrobenzene. =>
Chapter 17

7. Sulfonation
Sulfur trioxide, SO3, in fuming sulfuric acid is the electrophile.
=>
Chapter 17

8. Desulfonation
All steps are reversible, so sulfonic acid group can be removed by heating in dilute sulfuric acid.
This process is used to place deuterium in place of hydrogen on benzene ring.
Benzene-d6
=>
Chapter 17

9. Nitration of Toluene
Toluene reacts 25 times faster than benzene. The methyl group is an activator.
The product mix contains mostly ortho and para substituted molecules.
=>
Chapter 17

10. Sigma Complex
Intermediate is more stable if nitration occurs at the ortho or para position.
=>
Chapter 17

11. Energy Diagram
=>
Chapter 17

12. Activating, O-, P- Directing Substituents
Alkyl groups stabilize the sigma complex by induction, donating electron density through the sigma bond.
Substituents with a lone pair of electrons stabilize the sigma complex by resonance.
=>
Chapter 17

13. NITRATION OF ANISOLE

14. Nitration of Anisole ortho meta para activated ring actual products+
para

15. :
ortho
EXTRA!
meta
para :
EXTRA!

16. Energy Profiles meta ortho para Ea ortho-para director
NITRATION OF ANISOLE
benzenium
intermediate
RECALL:
HAMMOND
POSTULATE Ea
meta
benzenium
intermediates
have more
resonance
ortho
para
ortho-para
director

17. X BENZENIUM IONS GIVE ELIMINATION INSTEAD OF ADDITION
ADDITION REACTION
doesn’t happen
resonance would be lost X
ELIMINATION REACTION
restores aromatic ring
resonance
( 36 Kcal / mole )

18. The Amino Group
Aniline reacts with bromine water (without a catalyst) to yield the tribromide. Sodium bicarbonate is added to neutralize the HBr that’s also formed.
=>
Chapter 17

19. Summary of Activators
=>
Chapter 17

20. Deactivating Meta- Directing Substituents
Electrophilic substitution reactions for nitrobenzene are 100,000 times slower than for benzene.
The product mix contains mostly the meta isomer, only small amounts of the ortho and para isomers.
Meta-directors deactivate all positions on the ring, but the meta position is less deactivated =>
Chapter 17

21. Ortho Substitution on Nitrobenzene
=>
Chapter 17

22. Para Substitution on Nitrobenzene
=>
Chapter 17

23. Meta Substitution on Nitrobenzene
=>
Chapter 17

24. Energy Diagram
=>
Chapter 17

25. Structure of Meta- Directing Deactivators
The atom attached to the aromatic ring will have a partial positive charge.
Electron density is withdrawn inductively along the sigma bond, so the ring is less electron-rich than benzene =>
Chapter 17

26. Summary of Deactivators
=>
Chapter 17

27. More Deactivators
=>
Chapter 17

28. Halobenzenes
Halogens are deactivating toward electrophilic substitution, but are ortho, para-directing!
Since halogens are very electronegative, they withdraw electron density from the ring inductively along the sigma bond.
But halogens have lone pairs of electrons that can stabilize the sigma complex by resonance =>
Chapter 17

29. Sigma Complex for Bromobenzene
Ortho and para attacks produce a bromonium ion and other resonance structures.
=>
No bromonium ion possible with meta attack.
Chapter 17

30. Energy Diagram
=>
Chapter 17

31. Summary of Directing Effects
=>
Chapter 17

32. DIRECTIVITY OF SINGLE GROUPS

33. ortho, para - Directing Groups
Groups that donate
electron density
to the ring.
PROFILE: : E+
increased
reactivity
+I Substituent
+R Substituent ..
These groups also
“activate” the ring, or
make it more reactive.
CH3-O-
CH3- .. .. R-
CH3-N- ..
-NH2 ..
The +R groups activate
the ring more strongly
than +I groups.
-O-H ..

34. meta - Directing Groups
Groups that withdraw
electron density from
the ring.
PROFILE: d+ d- E+
decreased
reactivity
-I Substituent
-R Substituent
These groups also
“deactivate” the ring,
or make it less reactive. + + -
-SO3H

35. Halides - o,p Directors / Deactivating
THE EXCEPTION
Halides - o,p Directors / Deactivating
Halides represent a special case: .. : :
They are o,p directing groups
that are deactivating E+
They are o,p directors (+R effect )
They are deactivating ( -I effect )
Most other other substituents fall
into one of these four categories:
+R / -I / o,p / deactivating
1) +R / o,p / activating -F
-Cl
-Br -I
2) +I / o,p / activating
3) -R / m / deactivating
4) -I / m / deactivating

36. PREDICT !
o,p m
o,p m

37. DIRECTIVITY OF MULTIPLE GROUPS

38. GROUPS ACTING IN CONCERT
steric
crowding
o,p director
m-director
very
little
formed
HNO3
H2SO4
When groups direct to the
same positions it is easy to
predict the product.
major
product

39. GROUPS COMPETING X o,p-directing groups win over m-directing groups
too
crowded X
HNO3 +
H2SO4

40. RESONANCE VERSUS INDUCTIVE EFFECT
HNO3
H2SO4
major
product +I
resonance effects are more
important than inductive effects

41. SOME GENERAL RULES 1) Activating (o,p) groups (+R, +I) win over
deactivating (m) groups (-R,-I).
2) Resonance groups (+R) win over inductive (+I) groups.
3) 1,2,3-Trisubstituted products rarely form due to
excessive steric crowding.
4) With bulky directing groups, there will usually be more
p-substitution than o-substitution.
5) The incoming group replaces a hydrogen, it will not
usually displace a substituent already in place.

42. HOW CAN YOU MAKE ...
only,
no para

43. BROMINE - WATER REAGENT
PHENOLS AND ANILINES

44. BROMINE IN WATER .. .. .. .. .. .. - : : : : : .. .. .. .. .. .. : ..
This reagent works only with highly-activated rings
such as phenols, anisoles and anilines. .. .. .. .. .. .. - : : : : : .. .. .. .. + .. .. : + .. +
bromonium
ion
etc

45. PHENOLS AND ANILINES REACT
Br2
H2O
All available
positions are
bromiated.
Br2
H2O

46. Friedel-Crafts Alkylation
Synthesis of alkyl benzenes from alkyl halides and a Lewis acid, usually AlCl3.
Reactions of alkyl halide with Lewis acid produces a carbocation which is the electrophile.
Other sources of carbocations: alkenes + HF or alcohols + BF =>
Chapter 17

47. Examples of Carbocation Formation
=>
Chapter 17

48. Formation of Alkyl Benzene
=> + -
Chapter 17

49. Limitations of Friedel-Crafts
Reaction fails if benzene has a substituent that is more deactivating than halogen.
Carbocations rearrange. Reaction of benzene with n-propyl chloride and AlCl3 produces isopropylbenzene.
The alkylbenzene product is more reactive than benzene, so polyalkylation occurs =>
Chapter 17

50. Friedel-Crafts Acylation
Acyl chloride is used in place of alkyl chloride.
The acylium ion intermediate is resonance stabilized and does not rearrange like a carbocation.
The product is a phenyl ketone that is less reactive than benzene =>
Chapter 17

51. Mechanism of Acylation
=>
Chapter 17

52. Clemmensen Reduction
Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc.
=>
Chapter 17

53. Gatterman-Koch Formylation
Formyl chloride is unstable. Use a high pressure mixture of CO, HCl, and catalyst.
Product is benzaldehyde.
=>
Chapter 17

54. Chlorination of Benzene
Addition to the benzene ring may occur with high heat and pressure (or light).
The first Cl2 addition is difficult, but the next 2 moles add rapidly.
The product, benzene hexachloride, is an insecticide.
=>
Chapter 17

55. Catalytic Hydrogenation
Elevated heat and pressure is required.
Possible catalysts: Pt, Pd, Ni, Ru, Rh.
Reduction cannot be stopped at an intermediate stage.
=>
Chapter 17

56. Birch Reduction: Regiospecific
A carbon with an e--withdrawing group
is reduced.
A carbon with an e--releasing group
is not reduced.
=>
Chapter 17

57. Birch Mechanism
=>
Chapter 17

58. Side-Chain Oxidation
Alkylbenzenes are oxidized to benzoic acid by hot KMnO4 or Na2Cr2O7/H2SO4.
=>
Chapter 17

59. Side-Chain Halogenation
Benzylic position is the most reactive.
Chlorination is not as selective as bromination, results in mixtures.
Br2 reacts only at the benzylic position.
=>
Chapter 17