Download aryl halides

Aryl Halides
Ar-X
Organic compounds with a halogen atom attached to an
aromatic carbon are very different from those compounds
where the halogen is attached to an aliphatic compound.
While the aliphatic compounds readily undergo
nucleophilic substitution and elimination reactions, the
aromatic compounds resist nucleophilic substitution, only
reacting under severe conditions or when strongly
electron withdrawing groups are present ortho/para to the
halogen.
Aryl halides, syntheses:
1. From diazonium salts
Ar-N2+ + CuCl  Ar-Cl
Ar-N2+ + CuBr  Ar-Br
Ar-N2+ + KI
 Ar-I
Ar-N2+ + HBF4  Ar-F
2. Halogenation
Ar-H + X2, Lewis acid  Ar-X + HX
X2 = Cl2, Br2
Lewis acid = FeCl3, AlCl3, BF3, Fe…
reactions of alkyl halides
Ar-X
1. SN2
NR
2. E2
NR
3.  organo metallic compounds
similar
4. reduction
similar
Ag+
-OH
X
-OR
aryl halide
NH3
C C X
vinyl halide
-CN
ArH
AlCl3
NO REACTION
Bond Lengths (Å)
C—Cl
C—Br
CH3—X
1.77
1.91
C2H5—X
1.77
1.91
(CH3)3C—X
1.80
1.92
CH2=CH—X
1.69
1.86
C6H5—X
1.69
1.86
sp3
sp2
In aryl halides, the carbon to which the halogen is attached
is sp2 hybrizided. The bond is stronger and shorter than the
carbon-halogen bond in aliphatic compounds where the
carbon is sp3 hybridized. Hence it is more difficult to break
this bond and aryl halides resist the typical nucleophilic
substitution reactions of alkyl halides.
The same is true of vinyl halides where the carbon is also
sp2 hybridized and not prone to nucleophilic substitution.
In a manner analogous to the phenols & alcohols, we have
the same functional group in the two families, aryl halides
and alkyl halides, but very different chemistries.
Aryl halides, reactions:
1. Formation of Grignard reagent
2. EAS
3. Nucleophilic aromatic substitution (bimolecular displacement)
(Ar must contain strongly electron withdrawing groups ortho
and/or para to X)
4. Nucleophilic aromatic substitution (elimination-addition)
(Ring not activated to bimolecular displacement)
1)  Grignard reagent
Br
Mg
anhyd. Et2O
Mg
Cl
THF
MgBr
MgCl
2) EAS
The –X group is electron-withdrawing and
deactivating in EAS, but is an ortho/para director.
Br
Br
Br
NO2
+
HNO3, H2SO4
NO2
Br
SO3H
+ Br
H2SO4,SO3
Br
SO3H
Br
Br
Br2,Fe
+
Br
Br
CH3CH2-Br, AlCl3
CH2CH3
+
Br
CH2CH3
3) Nucleophilic aromatic substitution (bimolecular
displacement)
Ar must contain strongly electron withdrawing groups
ortho and/or para to the X.
Cl
NH2
NO2
NO2
+ NH3
NO2
NO2
Br
O2N
O2N
NO2
OCH3
NO2
+ NaOCH3
NO2
NO2
Cl
+ NaOH
NR
OH
350oC, 4500 psi
H+
OH
Cl
15% NaOH, 160oC
H+
NO2
NO2
OH
Cl
O2N
NO2
NO2
warm water
O2N
NO2
NO2
NH2
Cl
NH3, Cu2O, 200oC, 900 psi
NH2
Cl
NO2
NH3, 170oC
NO2
NO2
NO2
NH3
Cl
O2N
NO2
NO2
NH3, room temp.
O2N
NO2
NO2
bimolecular displacement (nucleophilic aromatic substitution)
mechanism:
Z
1)
2)
RDS
X + :Z
Z
X
X
Z
+ :X
Z
X
Z
Z
Z
X
X
X
Z
X
Z
G
X
G
If G is an electron withdrawing group in the ortho and
para positions, it will stabilize the intermediate anion.
evidence for the bimolecular displacement mechanism:
no element effect : Ar-I  Ar-Br  Ar-Cl  Ar-F
(the C—X bond is not broken in the RDS)
4) Elimination-Addition, nucleophilic aromatic substitution.
When the ring is not activated to the bimolecular
displacement and the nucleophile is an extremely good
one.
NH2
Br
+ NaNH2, NH3
Li
F
+
Li
H2O
Elimination-Addition mechanism (nucleophilic aromatic
substitution)
X
X
H
:
+ :NH2
1)
+ NH3
elimination
X
:
+ :X
2)
benzyne
:
3)
NH2
+ :NH2
addition
H
:
4)
NH2
NH2
+ NH3
+ :NH2
While the concept of “benzyne” may appear to be strange,
there is much evidence that this mechanism is correct.
NH2
Cl
*
NaNH2
*
+
*
NH2
NH3
47%
* = 14C
53%
Br
H3C
OCH3
NaNH2
NR
NH3
Cl
Cl
H
D
+ :NH2
benzyne intermediate has been trapped in a Diels-Alder
condensation:
+