Transcript Electrophilic Aromatic Substitution

Aromatic compounds
• Organic compound that contains a benzene
ring in its molecule is known as an aromatic
compounds.
• Sometimes called arenes.
• Molecular formula: C6H6
• Represented as a regular hexagon containing
an inscribed circle.
Structure of Benzene
• Can be represented in two abbreviated ways.
• The corner of each hexagon represents a carbon and a
hydrogen atom.
Kekulé Structure of Benzene
Molecular formula is C6H6
All the hydrogen atoms are equivalent
Each carbon atom must have four covalent bonds.
Resonance Structure
• Resonance theory: the structure of benzene is a resonance
hybrid structure of two Kekulé cononical forms.
• The hybrid structure is often represented by a hexagon
containing an inscribed circle.
represents a resonance hybrid between the two
• Hexagonal ring – 6 carbon-carbon bonds are
equal.
• Circle – delocalised electrons of the benzene
ring
Naming Aromatic
Compounds
• A substituted benzene is derived by replacing one
or more of benzene’s hydrogen atoms with an
atom or group of atoms.
• A monosubstituted benzene has the formula
C6H5G where G is the group that replaces a
hydrogen atom.
• All hydrogens in benzene are equivalent.
• It does not matter which hydrogen is replaced by
G.
Monosubstituted
Benzenes
• Some monosubstituted benzenes are
named by adding the name of the
substituent group as a prefix to the word
benzene.
• The name is written as one word.
nitro group
nitrobenzene
ethyl group
ethylbenzene
• Certain monosubstituted benzenes have special
names.
• These are parent names for further substituted
compounds.
hydroxy
group
methyl group
toluene
phenol
carboxyl group
amino group
benzoic acid
aniline
• Disubstituted Benzenes
•
Three isomers are possible when two substituents
replace hydrogen in a benzene molecule.
• The prefixes ortho-, meta- and para- (o-, m- and p-)
are used to name these disubstituted benzenes.
ortho disubstituted benzene
substituents on adjacent carbons
ortho-dichlorobenzene
(1,2-dichlorobenzene)
mp –17.2oC, bp 180.4oC
meta disubstituted benzene
substituents on adjacent carbons
meta-dichlorobenzene
(1,3-dichlorobenzene)
mp –24.82oC, bp 172oC
para disubstituted benzene
substituents are on opposite sides
of the benzene ring
para-dichlorobenzene
(1,4-dichlorobenzene)
mp 53.1, bp 174.4oC
When one substituent corresponds to a monosubstituted
benzene with a special name, the monosubstituted
compound becomes the parent name for the
disubstituted compound.
phenol
3-nitrophenol
When one substituent corresponds to a
monosubstituted benzene with a special name, the
monosubstituted compound becomes the parent
name for the disubstituted compound.
toluene
3-nitrotoluene
Tri- and Polysubstituted
Benzenes
• When a benzene ring has three or more
substituents, the carbon atoms in the ring are
numbered.
• Numbering starts at one of the substituent groups.
• The numbering direction can be clockwise or
counterclockwise.
• Numbering must be in the direction that gives the
substituent groups the lowest numbers.
6-chloro
clockwise
numbering
1-chloro
6
4-chloro
5
1
4
2
3
1,4,6-trichlorobenzene
counterclockwise
numbering
chlorine
substituents
have lower
numbers
4-chloro
2-chloro
1-chloro
2
3
1
4
6
5
1,2,4-trichlorobenzene
• When a compound is named as a derivative of
the special parent compound, the substituent of
the parent compound is considered to be C-1 of
the ring.
1
1
2
6
6
2
5
3
4
3
5
4
toluene
2,4,6trinitrotoluene
(TNT)
• When the hydrocarbon chain attached to the
benzene ring is small, the compound is named as
benzene derivative.
• Example:
CH2CH3
ethylbenzene
Benzene’s  electrons participate as a Lewis base
in reactions with Lewis acids
Lewis acid: electron pair acceptor
Lewis base: electron pair donor
Mechanism
E
r.d.s.
slow
E
H
E
H
:B
fast
-H(+)
E
+
(+)
HH-B
Halogenation of Benzene
Requires a Lewis acid catalyst
H
Cl2
FeCl3
H
Br2
FeBr3
Cl
+
Br
+
Reactivity: F2 >> Cl2 > Br2 >> I2
H-Cl
H-Br
Catalyst
Br
Br
Br Br
Br
Fe Br
+
+
Br
Br Fe Br
Br
d+
Br
Br
dBr Fe Br
Br
Mechanism (Cont’d)
H
Br
r.d.s.
slow
Br
H
Br
H
Br
H
+
Br
Br Fe Br
Br
Br
+
FeBr3
+
HBr
Nitration of Benzene
⊕
Electrophile = NO2 (nitronium ion)
Mechanism
H O
N O + O S O
O
O H
H
O
O
H
O
H
H
O
+
N
O
O
O
N
-H(+)
+
N O
O
O S O
O H
O
H
O
N O
O
N O
O
N O
H
H
H
Sulfonation
H O H
O S O +
H
O
O
+
O S
O
H
H O
H
O
O S O
H
O
+
H O
H O
O S O + O S O
O H
O H
O
O S O
H
O
r.d.s
O
S
O
O
H
O
S
O
O
H
repeat next slide
O
S
O
O
H
S
O
O
S
O
O
S
H
H
H
other (p,o)
resonance
structures
O
O
O
O
O
S
O
H
O
H
+
O
+
repeat
H
O
H
O
O S O
O H
O
S O
O H
H O
O S O
O H
H
H O
H
Sulfonation & Desulfonation-useful!
(heat)
Friedel–Crafts Alkylation
Electrophile = R
R = 2o or 3o
(not vinyl or aryl)
Non-reactive
46
Friedel–Crafts Acylation
O
Acyl group:
R
⊕
Electrophile is R–C≡O (acylium ion)
RX and Mechanism
O
O
+
d+
d+
Cl
Al4AlCl
Cl Cl
Cl
Cl
Cl
Al
d-
Cl
Cl
O
+
O
Cl
Cl
Al
Cl
Cl
O
O
-H(+)
R
R
R
R
H
O
H
O
H
Acid chlorides (or acyl chlorides)
Prep
Ch. 15 - 33
Limitations of Friedel–Crafts Reactions
(not formed)
Cl3Al
carbocations rearrangement
Ch. 15 - 35
Reason
1o cation (not stable)
3o cation
Ch. 15 - 36
Questions?
Ch. 15 - 3
Problems: Friedel–Crafts alkylations, acylations,
etc. with withdrawing groups & amines (basic)
generally give poor yields
deactivating gps
Basic amino groups (–NH2,–NHR, & –NR2) form
strong electron withdrawing gps with acids
Not Friedel-Crafts
reactive
Another problem: polyalkylations can occur
More common with activated aromatic rings
Electrophilic Aromatic
Substitution
Activating and Directing effects of
substituents already on the ring
Substituents effect reactivity &
regiochemistry of substitution
possibilities
Y
Y
Y
Y
E
E+
E
ortho
o
meta
m
E
para
p
Y = EDG (electron-donating group) or
EWG (electron-withdrawing group)
Ch. 15 - 48
Products of Nitration
ortho
CH3
eta
m
CH3
HNO3
63%
H2SO4
pa
ra
CH3
+
CH3
+
3%
NO2
34%
O2N
1 hr
NO2
CN
CN
HNO3
17%
H2SO4
CN
+
CN
+
81%
NO2
2%
O2N
48 hr
NO2
OH
OH
HNO3
50%
H2SO4
OH
+
0%
NO2
OH
+
50%
O 2N
NO2
0.0003 hr
relative to benzene
Ring is electron rich;
Ring reacts faster than
benzene with E+
Ring is electron poor;
Ring reacts slower
than benzene with E+
Ch. 15 - 50
Reactivity towards electrophilic
aromatic substitution
Regiochemistry: directing effect
General aspects
Either o-, p- directing or m-directing
Rate-determining-step:
aromatic ring p-electrons attacking the E
Y
Y
Y
E+
E
Y
E
E
ortho
Ch. 15 - 57
Y
Y
Y
Y
E
E
E
E+
para
Y
Y
Y
Y
E+
meta
E
E
E
Ch. 15 - 59
Effect of Electron-Donating (releasing) and
Electron-Withdrawing Groups
If G is electron-donating group
then reaction is faster than with benzene
G
G
G
G
d+
+
E(+)
d+
E
H
t.s.
stabilized
E
H
E
H
arenium ion
stabilized
Ch. 15 - 67
If G is an electron-withdrawing
then reaction is slower than with benzene
G
G
G
G
d+
+
E(+)
d+
E
H
t.s.
destabilized
E
H
E
H
arenium ion
destabilized
Ch. 15 - 68
Inductive and Resonance Effects: Orientation
Two types of EDG
(1)
(2)
resonance donation
of e(-)s into the
benzene ring
e(-)-inductive donation
(through σ bond)
Ch. 15 - 70
Two types of EDG
Positive resonance effect is stronger than positive inductive effect
(if the atom directly attacked to the benzene
is in the same row as carbon)
O
CH3
Ch. 15 - 71
EWG negative resonance (mesomeric)
or by negative inductive effect
O
Deactivate the ring by
resonance effect
Deactivate the ring by
negative inductive effect
Ch. 15 - 72
Meta-Directing Groups
EWG
EWG
E(+)
E
EWG = –COOR, –COR, –CHO, –CF3, –NO2, etc.
(EWG ≠ halogen)
Ch. 15 - 73
For example “if” ortho or para
CF3
CF3
NO2
O N O
CF3
CF3
NO2
NO2
etc.
(highly unstable,
negative inductive
effect of –CF3)
CF3
CF3
CF3
CF3
etc.
O N O
NO2
NO2
NO2
Ch. 15 - 74
meta
CF3
CF3
CF3
CF3
O N O
H
NO2
NO2
NO2
-H(+)
positive charge never
on a carbon adjacent
to the EWG
CF3
NO2
Ch. 15 - 76
Ortho–Para-Directing Groups
EDG
EDG
EDG
E(+)
E
+
E
EDG = –NR2, –OR, –OH, etc.
Ch. 15 - 77
EDG - para
extra resonance
structure, positive
resonance effect
O
H
O
H
N
(-)AlCl
N
H
N
O
O
O
H
H
N
N
4
Cl(+)
Cl
H
Cl
Cl
O
H
Cl
-H(+)
N
Cl
Ch. 15 - 78
EDG - ortho
(extra resonance)
O
H
N
H
Cl(+)
(-)AlCl
4
O
O
O
H
N
Cl
H
N
O
H
N
H
Cl
Cl
N
Cl
-H(+)
O
H
N
Cl
Ch. 15 - 79
EDG - (if meta: no extra stabilization)
O
H
O
O
H
N
(-)AlCl
Cl(+)
H
N
O
H
N
N
4
Cl
Cl
H
Cl
-H(+)
O
H
N
Cl
Ch. 15 - 80
halogens, two opposing effects
X
negative inductive
effect
X
X
X
X
positive resonance effect
halogens - weak deactivating
negative inductive effect > positive resonance
Ch. 15 - 81
But regiochemistry -o,p
Cl
Cl
H
O N O
Cl
NO2
Cl
NO2
Cl
NO2
-H(+)
Cl
Cl
NO2
NO2
extra
resonance
NO2
Cl
Cl
Cl
NO2
NO2
-H(+)
Cl
Cl
O N O
H NO
2
NO2
Ch. 15 - 83
Cl
Cl
Cl
Cl
O N O
NO2
meta: (no extra stabilization
resonance, higher
energy rx path)
NO2
H
NO2
-H(+)
Cl
NO2
Ch. 15 - 85
Ortho–Para Direction and
Reactivity of Alkylbenzenes
Ortho attack
Relatively
stable
contributor
Meta attack
Para attack
Relatively
stable
contributor
Classification of Substituents
Benzene
NO2
SO3H CO2H CHO
Br
R
F
more deactivating
+
NR 3
CN
OR
NH2
more activating
CR
COR
O
O
m-directing
deactivators
I
Cl
H Ar
o,p-directing
deactivators
NHCOCH3 OH
o,p-directing
activators
Product Distribution in Nitration
X
(Percent %)
ortho
meta
para
X
(meta-directing Deactivators)
ortho
meta
(Percent %)
para
(ortho- and para-directing Deactivators)
-N(CH3)3
2
89
11
-NO2
7
91
-CO2H 22
77
2
-CN
17
81
2
-CO2CH2CH3
28
72
2
-COCH3
26
72
2
-CHO 19
72
9
2
-F
13
1
86
-Cl
35
1
64
1
56
45
1
-Br
43
-I
54
(ortho- and para-directing Activators)
-CH3
-OH
50
63
3
0
50
-NHCOCH3 19
2
34
79
Summary
-NO2 or -CO2H, ortho- and para-NO2 or -CO2H, meta-
Deactivators
-Cl or -Br, meta-Cl or -Br, ortho- and para-H (unsubstituted)
-R or -Ar, meta-R or -Ar, ortho- and para-
Energy
-NH2 or -OH, meta-NH2 or -OH, ortho- and para[Carbocation
Intermediate]
Reactants
Reaction Progress
Activators
Additivity of substituent
effects in disubstituted
aromatic rings
• Rule 1: If the directing effects of two substituents
reinforce each other, the predicted product
predominates.
CH3 (o,p)
CH3
NO2
HNO3
H2SO4
CO2H (m)
CO2H
Additivity of substituent
effects…
• Rule 2: If the directing effects of two substituents oppose
each other, the more activating group dominates, but
mixtures often result.
NH2 (o,p; STRONG activator)
NH2
Br
Br2
CH3 (o,p;
(FeBr3 cat
not needed)
weak activator)
CH3
Additivity of substituent
effects…
• Rule 3: Substitution almost never occurs between two
substituents meta to each other.
CH3 (o,p)
X (too crowded)
CH3
CH3
HO3S
SO3
Cl
(o,p)
+
H2SO4
Cl
SO3H
Cl
CH3
SO3H
but not:
Cl
Additivity of substituent
effects…
• Rule 4: With a bulky o,p- director and/or a bulky
electrophile, para substitution predominates.
O
O
OCCH3 (o,p; BULKY)
OCCH3
SO3
H2SO4
(HSO3+ is a
BULKY electrophile)
SO3H