The document summarizes key concepts in aromatic substitution reactions. It describes the electrophilic aromatic substitution mechanism where an electrophile such as the nitronium ion attacks the aromatic ring. It outlines different electrophiles used such as halogens, acyl groups, and alkyl groups. It discusses the effects of different substituents on the ring in terms of their electronic properties as either activating or deactivating groups, and whether they are ortho/para or meta directors. Examples of industrially important aromatic compounds formed by substitution reactions are also mentioned, such as TNT.

1. Aromatic Substitution
Dr. Nilesh R.Thakare
ElectrophilicAromatic Electrophilic Substitution
Dr. Nilesh R Thakare

2. Sect. 22.1 Nomenclature
benzene
CH3
toluene
Cl
chlorobenzene
OH
phenol
NH2
O
OH
aniline benzoic acid
O
H
benzaldehyde
NO2
nitrobenzene
Aromatic Substitution

3. Nomenclature-- examples
O
OH
benzoic acid
O
H
Group ortho
meta or 3
para or 4
or 2
NO2
3-nitro (IUP AC)
m-nitrobenzoic acid (common)
Cl
4-chlorobenzaldehyde (IUPAC)
p-chlorobenzaldehyde (common)
Aromatic Substitution

4. Chapter 22: Aromatic Substitutions,
Monosubstitution reactions on benzene
Sect. 22.2 Electrophilic aromatic substitution mechanism
Sect. 22.5 Nitration
Sect. 22.6. Halogenation
Sect. 22.7 Friedel-Crafts Reactions
Sect. 22.8 Sulfonation Reactions (skip fall 2006)
Aromatic Substitution

5. Sect. 22.2 Electrophilic aromatic
substitution.
E+
SLOW
E
H
H
E
H
E
H
resonance stabilized cation
E
H
:B
"base"
re-aromatizeE
+ HB
delocalized
cation
Aromatic Substitution

6. Sect. 22.5: Nitration
 conc. HNO3 and H2SO4 react to make electrophile, NO2
+
 nitro aromatics are important intermediates
 reduction of nitro groups give anilines
N OO
nitronium ion
NO2
H
HSO4
NO2
H2SO4
HNO3
H2SO4
NO2
NO2
reduce NH2
reducing agents: LiAlH4 or H2 / Pd(C) or Sn / HCl or Fe / HOAc
+ H2O
Aromatic Substitution

7. Mechanism of Aromatic
Nitration
Step 1: Where does the
electrophile come from?
Aromatic Substitution
HO N
O
O
+ H2SO4
O
H H
+N
Nitronium ion
O O
O N
O
OH
H
O N
O
OH
H
HSO4
Nitronium ion (NO2
+) is the electrophile that reacts
with the benzene ring.

8. Mechanism of Aromatic
Nitration (Step 2)
H
+ NO2
slow
H
NO2
H
NO2
H
NO2
a resonance-stabilized arenium ion
Aromatic Substitution

9. Mechanism of Aromatic
Nitration (Step 3)
H
NO2 + HSO4
fast
NO2
+
this represents the
resonance hybrid
of the arenium ion
H2SO4
H
NO2
O -S
O
O
OH
NO2
S
O
O
OHH-O
Aromatic Substitution

10. Sect. 22.6: Halogenation
 active electrophile is a bromonium or chloronium ion
 need Lewis acid catalyst ( FeX3 ) to activate X2
bomonium ion
Br
H
Br
Br
HBr
Br2
FeBr3
Br
+ HBr
Br
Br2 + FeBr3
Cl2
FeCl3
Cl
+ HCl
(iodination requires special conditions)
mechanism:
Br + FeBr4
Aromatic Substitution

11. Sect. 22.7: Friedel-Crafts Alkylation
 alkyl halide + AlCl3 -->carbocation + AlCl3X-
 watch out for carbocation rearrangements!
 more than one alkylation can occur --> mixtures!
+ Br + HBr
AlCl3 (cat)
CH2Cl2
+ + HBr
AlCl3 (cat)
CH2Cl2
Br
Aromatic Substitution

12. Friedel-Crafts Acylation
 acid chloride + AlCl3 --> acylium ion + AlCl4
-
 cation rearrangements are NOT observed!
 acylation will only occur ONCE...
 reaction VERY sensitive to substituents-- an acyl group
prevents further reaction
+
Cl
O
AlCl3 (cat)
O
+ HCl
Cl
O
AlCl4C O
AlCl3
O
an acylium ion
Aromatic Substitution

13. Aromatic Substitution
H
O H
O
Two other
resonance
structures
H+_
O

14. Aromatic substitution on
Benzene
 Sect. 22.8: Sulfonation (skip, fall 06)
 Sect. 22.9: Summary
Aromatic Substitution

15. Sect. 22.10 and 22.11:
Directing effects
 methoxy group releases electrons by resonance effect:
ortho and para director
 nitro group withdraws electrons by inductive and
resonance effect: meta director
Aromatic Substitution

16. These are ortho and para
directors! All are electron
releasing!!
Aromatic Substitution
R = H or alkyl
-O-R
O
-N-C-R
O
H
-O-C-R
-O-H -R -X-NR2
..
..
.. ..
..
..
..
..
..
..
.
.

17. Aromatic Substitution
All ortho/para directing groups have pairs of
electrons next to the benzene ring!
The only exception are alkyl groups. They are also
ortho/para directors.

18. Why do ortho/para groups direct as
they do? Resonance!!
O CH3
H3C
O
Cl
AlCl3
H3C
O
AlCl4
_
O
CH3
H
H
O
CH3
O
CH3
H
O
CH3
O
CH3
H
O
CH3
O
CH3
H
O
CH3
O
CH3
Extra resonance
structure from lone
pair on oxygen!
Ortho would work
too.
Meta won't work!
can't put + next
to O-CH3
Aromatic Substitution

19. These are meta directors! All
are electron withdrawing!!
R
O
H
O
O-R
O
NH2
O
N
CH3
CH3
CH3
C
F
F
F
N
O
O
S
O
O
OH
Notice! These groups have electronegative elements next to the
benzene ring! There are NO non-bonded electrons next to the ring!
C N
Aromatic Substitution

20. Now let’s look at a meta
directing group
C
O
O
CH3
+ HNO3
H2SO4
15°C
C
O
O
CH3
+ H2O
NO2H
Aromatic Substitution
This is an example of Electrophilic Aromatic
Substitution (EAS).

21. Why does the nitration reaction take
place preferentially at the meta
position?
Aromatic Substitution
Let’s ask a “what if” question.

22. WWU-Chemistry
ortho
meta
para
BAD!
BAD!
H
NO2
C
O OCH3
H
NO2
C
O OCH3
H
NO2
C
O OCH3

C
O OCH3
C
O OCH3
C
O OCH3
H
NO2
H
NO2
H
NO2
C
O OCH3
C
O OCH3
C
O OCH3
H NO2 H NO2 H NO2



23. meta substitution
preferred because the +
charge is never next to the
CO2R group
Aromatic Substitution

24. Activation during substitution
All ortho and para directing groups are
activating relative to benzene, except
halogen substituents. Halogens are weakly
deactivating but are still o, p- directors.
G
H E
+
Electron releasing groups (G) help stabilize
the + in the ring introduced by the electrophile.
This increases the rate of substitution!
Aromatic Substitution

25. Deactivation during substitution
 All meta directors are strongly
deactivating relative to benzene.
G
H E
+
Electron withdrawing groups (G) intensify
the + in the ring introduced by the electrophile.
This slows the substitution reaction!
Aromatic Substitution

26. Sect. 22.12 and 22.17:
Some synthetic examples
involving aromatic
substitution
Aromatic Substitution

27. Aromatic Substitution
• ortho/para directors can work together with
meta directors. They reinforce each other.
O-CH3
HNO 3
O-CH3
NO2
HNO 3
O-CH3
NO2
NO2
H2SO4
H2SO4
ortho/ para director
ortho/para
meta

28. Aromatic Substitution
Strong o/ p directors win over weak o, p
and meta directors.
OH
CH3
Br2
FeBr3
OH
CH3
Br

29. Aromatic Substitution
Substitution RARELY occurs in-between two
substituents--too hindered!
CH3
CH3
H3C
O
Cl
AlCl3
CH3
CH3
O
CH3
nothing here!

30. Aromatic Substitution
Some groups can be modified to change their
directing effects.
CH3
ortho/para
director
KMnO4
O OH
meta directorBr2
FeBr3
CH3
Br
CH3
Br
Br2
FeBr3
O OH
BrKMnO4 KMnO4
Br
O OH O OH
Br
3-bromobenzoic acid
2-bromobenzoic acid 4-bromobenzoic acid

31. Good stuff! Order of reaction is critical!
CH3
KMnO4
O OH
CH3
NO2
CH3
NO2
HNO 3
H2SO4
O OH
NO2
HNO 3
H2SO4
O OH
O OH
NO2
NO2
2-nitrobenzoic acid
4-nitrobenzoic acid 3-nitrobenzoic acid
KMnO4
KMnO4
Aromatic Substitution

32. Some more good stuff!
Aromatic Substitution
H3C
O
Cl
AlCl3
O CH3
Br2
FeBr3
Br
O CH3
O CH3
Br
Br2
FeBr3
Br
H3C
O
Cl
AlCl3
meta director
ortho/para director

33. An explosive!
CH3
NO2
NO2
O2N
2,4,6-trinitrotoluene (TNT)
Aromatic Substitution

34. CH3
HNO 3
H2SO4
CH3
NO2
CH3
NO2
Easy!
HNO 3
H2SO4
CH3
NO2
NO2
more difficult
Heat it!
HNO 3
H2SO4
Even more difficult
so really heat it!
CH3
NO2
NO2
O2N
Aromatic Substitution
2,4,6-Trinitrotoluene = TNT

35. Some miscellaneous examples
 Nitration of 3-nitrobenzoic acid
 Acylation of 1,3-dimethylbenzene
 Acylation of 1,4-dimethylbenzene
 Make 2-methyl-1-phenylpropane
Aromatic Substitution

36. Sect. 22.16 Aromaticity and
Huckel’s Rule
+ _
Cation Anion
Aromatic Substitution
Aromatic compounds 4n + 2 pi electrons
n = 1 6 pi electrons systems
:

37. Aromatic Substitution
H
H
H
Empty
p-orbital
6-pi electrons
This is a n = 1
with 6 pi electrons
Aromatic!

38. Other n = 1 aromatics
N OS
H
Aromatic Substitution
: : : : :
6 electrons 6 electrons, one pair
not involved!
6 electrons, one
pair not involved!
All are aromatic!

39. Aromatic Substitution
O
Oxygen has two pairs, but only one pair is in the
pi system (p-orbital).
rehydridize the oxygen
atom from sp3
to sp2
This system is a n = 1 system, with 6 pi electrons
This compound is AROMATIC!

40. n = 0 aromatic: 2 pi electrons
+
Aromatic Substitution

41. Aromatic Substitution
HH
H
2 pi electrons
Aromatic!
H
H
H
H
Cyclopropene is not aromatic, you
need p orbital at all positions!

42. Some Antiaromatic
compounds
4 electrons 8 electrons
_
4 electrons
Aromatic Substitution
:
Not aromatic!

43. Diazonium ions, Azo Dyes and the
Sandmeyer Reaction- from Chapter 23
(not covered 06)
Aromatic Substitution
Sect 23.16: Diazonium ion formation
Sect 23.17: Sandmeyer reaction
Sect 23.19: Azo dyes