Post on 19-Dec-2015
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Aromatic Substitution Aromatic Substitution
Electrophilic
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Sect. 22.1 NomenclatureSect. 22.1 Nomenclature
benzene
CH3
toluene
Cl
chlorobenzene
OH
phenol
NH2
O
OH
aniline benzoic acid
O
H
benzaldehyde
NO2
nitrobenzene
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Nomenclature-- examples Nomenclature-- examples
O
OH
benzoic acid
O
H
Group ortho
meta or 3
para or 4
or 2
NO2
3-nitro (IUPAC)
m-nitrobenzoic acid (common)
Cl
4-chlorobenzaldehyde (IUPAC)
p-chlorobenzaldehyde (common)
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Chapter 22: Aromatic Substitutions,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)
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Sect. 22.2 Electrophilic aromatic Sect. 22.2 Electrophilic aromatic substitution.substitution.
E+SLOW
E
HH
E
H
E
H
resonance stabilized cation
E
H
:B
"base"
re-aromatizeE
+ HB
delocalizedcation
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Sect. 22.5: NitrationSect. 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
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Mechanism of Aromatic NitrationMechanism of Aromatic NitrationStep 1: Where does the electrophile Step 1: Where does the electrophile
come from?come from?
HO N
O
O
+ H2SO4
OH 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.
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Mechanism of Aromatic Mechanism of Aromatic Nitration (Step 2)Nitration (Step 2)
H
+ NO2
slow
H
NO2
H
NO2
H
NO2
a resonance-stabilized arenium ion
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Mechanism of Aromatic Mechanism of Aromatic Nitration (Step 3)Nitration (Step 3)H
NO2 + HSO4
fast
NO2
+
this represents theresonance hybridof the arenium ion
H2SO4
H
NO2
O -S
O
O
OH
NO2
S
O
O
OHH-O
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Sect. 22.6: HalogenationSect. 22.6: Halogenation• active electrophile is a bromonium or chloronium ion
• need Lewis acid catalyst ( FeX3 ) to activate X2
bomonium ion
Br
HBr
Br
HBr
Br2
FeBr3
Br
+ HBr
Br
Br2 + FeBr3
Cl2
FeCl3
Cl
+ HCl
(iodination requires special conditions)
mechanism:
Br + FeBr4
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Sect. 22.7: Friedel-Crafts Sect. 22.7: Friedel-Crafts AlkylationAlkylation
• alkyl halide + AlCl3 -->carbocation + AlCl3X-
• watch out for carbocation rearrangements!
• more than one alkylation can occur --> mixtures!
+ Br + HBrAlCl3 (cat)
CH2Cl2
+ + HBrAlCl3 (cat)
CH2Cl2Br
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Friedel-Crafts AcylationFriedel-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
OAlCl3 (cat)
O
+ HCl
Cl
O
AlCl4C OAlCl3
O
an acylium ion
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HO H
O
Two otherresonancestructures
H+_
O
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Aromatic substitution on Aromatic substitution on BenzeneBenzene
• Sect. 22.8: Sulfonation (skip, fall 06)
• Sect. 22.9: Summary
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Sect. 22.10 and 22.11: Directing Sect. 22.10 and 22.11: Directing effectseffects
• methoxy group releases electrons by resonance effect: ortho and para director
• nitro group withdraws electrons by inductive and resonance effect: meta director
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These are These are ortho and paraortho and para directors! All are electron directors! All are electron
releasing!! releasing!!
R = H or alkyl
-O-R
O
-N-C-R
O
H
-O-C-R
-O-H -R -X-NR2
..
..
.. ..
..
..
..
..
..
..
..
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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.
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Why do ortho/para groups direct as Why do ortho/para groups direct as they do? Resonance!!they do? Resonance!!
O CH3
H3C
O
ClAlCl3
H3C
O
AlCl4
_
O
CH3H
HO
CH3
OCH3
HO
CH3
OCH3
HO
CH3
OCH3
HO
CH3
OCH3
Extra resonancestructure from lonepair on oxygen!Ortho would worktoo.
Meta won't work!can't put + nextto O-CH3
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These are These are meta meta directors! All are directors! All are electron withdrawing!!electron withdrawing!!
R
O
H
O
O-R
O
NH2
O
N
CH3
CH3
CH3
C
F
FF
NO
OSO
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
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Now let’s look at a meta directing Now let’s look at a meta directing groupgroup
CO
O
CH3
+ HNO3
H2SO4
15°C
CO
O
CH3
+ H2O
NO2H
This is an example of Electrophilic Aromatic Substitution (EAS).
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Why does the nitration reaction take Why does the nitration reaction take place preferentially at the place preferentially at the metameta
position?position?
Let’s ask a “what if” question.
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ortho
meta
para
BAD!
BAD!
H
NO2
CO OCH3
H
NO2
CO OCH3
H
NO2
CO OCH3
CO OCH3
CO OCH3
CO OCH3
H
NO2
H
NO2
H
NO2
CO OCH3
CO OCH3
CO OCH3
H NO2 H NO2 H NO2
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meta substitution preferred because meta substitution preferred because the + charge is never next to the the + charge is never next to the
COCO22R groupR group
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Activation during substitution 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!
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Deactivation during substitutionDeactivation 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!
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Sect. 22.12 and 22.17: Some Sect. 22.12 and 22.17: Some synthetic examples involving synthetic examples involving
aromatic substitutionaromatic substitution
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• ortho/para directors can work together with meta directors. They reinforce each other.
O-CH3HNO3
O-CH3
NO2
HNO3
O-CH3
NO2
NO2
H2SO4H2SO4
ortho/ para directorortho/parameta
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Strong o/ p directors win over weak o, p and meta directors.
OH
CH3
Br2
FeBr3
OH
CH3
Br
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Substitution RARELY occurs in-between two substituents--too hindered!
CH3
CH3
H3C
O
Cl
AlCl3
CH3
CH3
O CH3
nothing here!
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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
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Good stuff! Order of reaction is critical! Good stuff! Order of reaction is critical! CH3
KMnO4
O OH
CH3
NO2
CH3
NO2
HNO3
H2SO4
O OH
NO2
HNO3
H2SO4
O OHO OH
NO2
NO2
2-nitrobenzoic acid4-nitrobenzoic acid 3-nitrobenzoic acid
KMnO4KMnO4
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H3C
O
Cl
AlCl3
O CH3
Br2
FeBr3Br
O CH3
O CH3
Br
Br2
FeBr3
Br
H3CO
Cl
AlCl3
meta director
ortho/para director
Some more good stuff!Some more good stuff!
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An explosive!An explosive!
CH3
NO2
NO2
O2N
2,4,6-trinitrotoluene (TNT)
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CH3
HNO3
H2SO4
CH3
NO2
CH3
NO2
Easy!
HNO3
H2SO4
CH3
NO2
NO2
more difficultHeat it!
HNO3
H2SO4
Even more difficultso really heat it!
CH3
NO2
NO2O2N
2,4,6-Trinitrotoluene = TNT
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Some miscellaneous examplesSome miscellaneous examples
• Nitration of 3-nitrobenzoic acid
• Acylation of 1,3-dimethylbenzene
• Acylation of 1,4-dimethylbenzene
• Make 2-methyl-1-phenylpropane
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Sect. 22.16 Aromaticity and Sect. 22.16 Aromaticity and Huckel’s RuleHuckel’s Rule
Aromatic compounds 4n + 2 pi electronsn = 1 6 pi electrons systems
+ _
Cation Anion
:
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H
H
H
Empty p-orbital
6-pi electrons
This is a n = 1with 6 pi electrons
Aromatic!
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Other n = 1 aromaticsOther n = 1 aromatics
N OS
H
: : : : :
6 electrons 6 electrons, one pairnot involved!
6 electrons, one pair not involved!
All are aromatic!
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O
Oxygen has two pairs, but only one pair is in thepi 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!
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n = 0 aromatic: 2 pi electronsn = 0 aromatic: 2 pi electrons
+
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HH
H
2 pi electrons
Aromatic!
H
H
H
H
Cyclopropene is not aromatic, you need p orbital at all positions!
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Some Antiaromatic compoundsSome Antiaromatic compounds
4 electrons 8 electrons
_
4 electrons
:
Not aromatic!
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Diazonium ions, Azo Dyes and Diazonium ions, Azo Dyes and the Sandmeyer Reactionthe Sandmeyer Reaction- from - from
Chapter 23 (not covered 06)Chapter 23 (not covered 06)
Sect 23.16: Diazonium ion formationSect 23.17: Sandmeyer reaction Sect 23.19: Azo dyes