Transcript 9 - Wiley

9
Introduction to
Organic
Chemistry
2 ed
William H. Brown
9-1
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9
Aromatic
Compounds
Chapter 9
9-2
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Benzene - Kekulé
• The first structure for benzene was proposed by
August Kekulé in 1872
H
H
H
C
H
C
C
C
C
C
H
H
H
H
C
H
C
C
C
C
C
H
H
H
• this structure, however, did not account for the unusual
chemical reactivity of benzene
9-3
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Benzene - VB Model
• The concepts of hybridization of atomic orbitals
and the theory of resonance, developed in the
1930s, provided the first adequate description of
benzene’s structure
• the carbon skeleton is a regular hexagon, with all
C-C and H-C-C bond angles 120°
H
120°
H
C
1.09 Å
H
120°
C
120°
C
C
C
H
1.39 Å

C-
sp 2 -sp 2
CH
sp 2 -1s
H
9-4
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Benzene - VB Model
• each carbon has one unhybridized 2p orbital containing
one electron
• overlap of the six parallel 2p orbitals forms a
continuous pi cloud
• the electron density of benzene lies in one torus above
the plane of the ring and a second below it
H
H
C
H
C
C
C
C
H
H
C
H
9-5
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Benzene - Resonance
• We often represent benzene as a hybrid of two
equivalent Kekulé structures
• each makes an equal contribution to the hybrid, and
thus the C-C bonds are neither double nor single, but
something in between
9-6
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Benzene - Resonance
• Resonance energy: the difference in energy
between a resonance hybrid and the most stable
of its hypothetical contributing structures in
which electrons are localized on particular atoms
and in particular bonds
• One way to estimate the resonance energy of
benzene is to compare the heats of hydrogenation
of benzene and cyclohexene
9-7
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Benzene - Resonance
Ni
+H2
1-2 atm.
Cyclohexene
+ 3 H2
Benzene
DH° = -28.6 kcal/mol
(-120 kJ/mol)
Cyclohexane
Ni
200-300 atm
Cyclohexane
DH° = -49.8 kcal/mol
(-208 kJ/mol)
• comparing 3 x DH° for cyclohexene with DH° for
benzene, it is estimated that the resonance energy of
benzene is approximately 36 kcal/mol
9-8
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Heterocyclic Aromatics
• Heterocyclic compound: contains one or more
atoms other than carbon in a ring
• Pyridine and pyrimidine are heterocyclic analogs
of benzene. Each is aromatic.
4
4
3
5
6
2
6
••
5
3
N
N1
2
N1
••
Pyridine
Pyrimidine
••
9-9
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Pyridine
• Pyridine has a resonance energy of 32 kcal/mol,
slightly less than that of benzene
this sp2 hybrid orbital is
•
perpendicular to the six
2p orbitals of the pi system
•
•
•
•
•
N
this pair of electrons
is not a part of the
aromatic sextet
9-10
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Furan
• Of the two unshared pairs of electrons on the
oxygen atom of furan, one is and one is not a part
of the aromatic sextet
• the resonance energy of furan is 16 kcal/mol
this pair of electrons
is a part of the
aromatic sextet
•
•
•
• O
this pair of
electrons
is not
9-11
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Other Heterocyclics
CH2 CH2 NH2
HO
N
H
Indole
N
H
Serotonin
(a neurotransmitter)
NH2
N
N
N
H
Purine
N
N
N
N
N
H
Adenine
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9-12
9 Nomenclature
• Monosubstituted alkylbenzenes are named as
derivatives of benzene
• many common names are retained
CH 2 CH 3
Benzene
Ethylbenzene
CH3
Toluene
CH(CH 3 ) 2
Cumene
CH=CH 2
Styrene
9-13
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Nomenclature
• these common names are also retained
OH
Phenol
Aniline
CHO
Benzaldehyde
NH 2
CO 2 H
Benzoic acid
OCH 3
Anisole
9-14
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Nomenclature
• benzyl and phenyl groups
CH 3
Benzene
Phenyl
group
C 6 H5
Benzyl group
CH 3
C C
H3 C
Toluene
CH 2 -
C 6 H5 CH 2 Cl
H
Benzyl chloride
(Z)-2-Phenyl-2-butene
9-15
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Disubstituted Benzenes
• Locate the two groups by numbers or by the
locators ortho (1,2-), meta (1,3-), and para (1,4-)
• where one group imparts a special name, name the
compound as a derivative of that molecule
CH3
NH 2
CO2 H
NO2
Cl
Br
4-Bromotoluene
(p-Bromotoluene)
3-Chloroaniline 2-Nitrobenzoic acid
(m-Chloroaniline) (o-Nitrobenzoic acid)
9-16
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Disubstituted Benzenes
• where neither group imparts a special name, locate the
groups and list them in alphabetical order
CH 2 CH 3
4
3
NO 2
2
Br
1
2
1
Cl
1-Chloro-4-ethylbenzene
(p-Chloroethylbenzene)
1-Bromo-2-nitrobenzene
(o-Bromonitrobenzene)
9-17
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Polysubstituted Derivs
• if one group imparts a special name, name the molecule
as a derivative of that compound
• if no group imparts a special name, list them in
alphabetical order, giving them the lowest set of
numbers
NO 2
OH
4
Br 6 1 2 Br
5
3
3
5
4
Br
2,4,6-Tribromophenol
2
6
1
Br
CH 2 CH 3
2-Bromo-1-ethyl-4-nitrobenzene
9-18
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 PAHs
• Polynuclear aromatic hydrocarbons (PAHs)
contain two or more aromatic rings, each pair of
which shares two ring carbons
Naphthalene
Anthracene
Phenanthrene
9-19
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 PAHs
Benzo[a]pyrene
Coronene
9-20
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Phenols
• The functional group of a phenol is an -OH group
bonded to a benzene ring
OH
OH
OH
OH
OH
CH 3
OH
Phenol 3-Methylphenol 1,2-Benzenediol 1,4-Benzenediol
(m-Cresol)
(Catechol)
(Hydroquinone)
9-21
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Acidity of Phenols
• Phenols are significantly more acidic than
alcohols, compounds that also contain the -OH
group
Phenol: pKa = 9.95
-
OH + H2 O
O
Ethanol: pKa = 15.9
CH 3 CH 2 OH + H2 O
CH 3 CH 2 O
+ H 3 O+
-
+ H 3 O+
9-22
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Acidity of Phenols
• We account for the increased acidity of phenols
relative to alcohols in the following way
• delocalization of the negative charge on a phenoxide
ion stabilizes it relative to an alkoxide ion
• because a phenoxide ion are more stable than an
alkoxide ion, phenols are stronger acids than alcohols
• Note that while this reasoning helps us to
understand why phenols are more acidic than
alcohols, it does not give us any way to predict
how much stronger they are
9-23
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Acidity of Phenols
••
O
••
••
••
••
••
O
O
••
••
••
O
••
••
H
••
••
These 2 Kekulé structures
are equivalent
O
••
H
H ••
These three contributing structures
delocalize the negative charge onto
carbon atoms of the ring
9-24
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Acidity of Phenols
• Ring substituents, particularly halogen and nitro
groups, have marked effects on the acidity of
phenols
OH
Phenol
pKa 9.95
OH
Cl
p-Chlorophenol
pKa 9.18
OH
NO2
p-Nitrophenol
pKa 7.15
9-25
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Acidity of Phenols
• Phenols are weak acids and react with strong
bases to form water-soluble salts
• water-insoluble phenols dissolve in NaOH(aq)
OH
Phenol
pKa = 9.95
(stronger acid)
+
NaOH
Sodium
hydroxide
(stronger base)
O- Na + +
H2 O
Water
Sodium phenoxide pKa = 15.7
(weaker base) (weaker acid)
9-26
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Acidity of Phenols
• most phenols do not react with weak bases such as
NaHCO3; they do not dissolve in aqueous NaHCO3
OH +
Phenol
pKa = 9.95
(Weaker acid)
NaHCO 3
Sodium
bicarbonate
(Weaker base)
O Na + +
H2 CO3
Carbonic acid
Sodium phenoxide
pKa = 6.36
(Stronger base)
(Stronger acid)
9-27
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Benzylic Oxidation
• Benzene is unaffected by strong oxidizing agents
such as H2CrO4 and KMnO4
• halogen and nitro substituents are unaffected by these
reagents
• an alkyl group with at least one hydrogen on the
benzylic carbon are oxidized to a carboxyl group
O2 N
Cl
CH 3
2-Chloro-4-nitrotoluene
K2 Cr 2 O7
H 2 SO4
O2 N
Cl
CO2 H
2-Chloro-4-nitrobenzoic acid
9-28
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Benzylic Oxidation
• if there is more than one alkyl group, each is oxidized to
a -CO2H group
H3 C
CH3
K2 Cr 2 O7
1,4-Dimethylbenzene
(p-xylene)
H2 SO4
O
HOC
O
COH
1,4-Benzenedicarboxylic acid
(terephthalic acid)
9-29
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Rexns of Benzene
• The most characteristic reaction of aromatic
compounds is substitution at a ring carbon
Halogenation:
H + Cl 2
FeCl 3
Cl
+
HCl
Chlorobenzene
Nitration:
H + HNO 3
H2 SO 4
NO2
+ H2 O
Nitrobenzene
9-30
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Rexns of Benzene
Sulfonation:
H2 SO 4
H + SO 3
SO 3 H
Benzenesulfonic acid
Alkylation:
AlX 3
H + RX
R
+
HX
An alkylbenzene
Acylation:
O
H
+ RCX
O
A lX3
CR + HX
An acylbenzene
9-31
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Rexns of Benzene - EAS
• Electrophilic aromatic substitution: a reaction in
which a hydrogen atom of an aromatic ring is
replaced by an electrophile
H
+
+ E
E
+
H
+
• We study
• several common types of electrophiles,
• how each is generated, and
• the mechanism by which it replaces hydrogen
9-32
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Chlorination
• Halogenation requires a Lewis acid catalyst, such
as AlCl3 or FeCl3
• Step 1: formation of a chloronium ion
Cl
Cl
Cl
••
••
••
••
••
••
+
Fe
Cl
chloronium
ion
Cl
Cl
••
••
Cl
Fe
+
Cl Fe Cl4
••
Cl
••
••
••
+
••
Cl
••
Cl
9-33
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Chlorination
• Step 2: attack of the chloronium ion on the ring to give
a resonance-stabilized cation intermediate
+ Cl
+
+
rate-limiting
step
H
H
H
+
Cl
Cl
+ Cl
Resonance-stabilized cation intermediate
9-34
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Chlorination
• Step 3: proton transfer to regenerate the aromatic
character of the ring
Cl FeCl3
+
H
fast
Cl + HCl + FeCl3
Cl
Cation
Chlorobenzene
intermediate
• The mechanism for bromination is the same as
that for chlorination
9-35
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 EAS: General Mechanism
• A general mechanism
Step 1:
+
H + E
ratelimiting step
Electrophile
+
Step 2:
H
E
fast
+
H
E
Resonance-stabilized
cation intermediate
E + H+
• General question: what is the electrophile in an
EAS and how is it generated?
9-36
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Nitration
• The electrophile is NO2+, generated as follows
H
+
H O NO 2 + HSO 4
••
••
H O NO2 + H O SO 3 H
••
Nitric acid
H O
••
••
NO2
+ ••
+ O=N=O
Nitronium ion
••
••
••
H
••
H
H +O
9-37
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Nitration
• The particular value of nitration is that the nitro
group can be reduced to a 1° amino group
O2 N
CO 2 H + 3 H 2
Ni
(3 atm)
4-Nitrobenzoic acid
H2 N
CO2 H + 2 H2 O
4-Aminobenzoic acid
9-38
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Friedel-Crafts Alkylation
• Friedel-Crafts alkylation forms a new C-C bond
between a benzene ring and an alkyl group
CH3
+
Benzene
CH3 CHCl
AlCl 3
2-Chloropropane
(Isopropyl chloride)
CH( CH 3 ) 2 +
HCl
Cumene
(Isopropylbenzene)
9-39
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Friedel-Crafts Alkylation
• Step 1: formation of an alkyl cation as an ion pair
Cl
••
R
••
Cl
••
+
Al
Cl
Cl
+
••
R
Cl
-
Cl Al Cl
••
Cl
+
-
R A lCl4
An ion pair
containing
a carbocation
9-40
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Friedel-Crafts Alkylation
• Step 2: attack of the alkyl cation on the aromatic ring
+ R+
+
H
R
+
H
H
R
+ R
The positive charge is delocalized onto
three atoms of the ring
9-41
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Friedel-Crafts Alkylation
• Step 3: proton transfer to regenerate the aromatic
character of the ring
+
Cl A lCl 3
H
R
R + A lCl 3
+ HCl
9-42
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Friedel-Crafts Acylation
• Friedel-Crafts acylation forms a new C-C bond
between a benzene ring and an acyl group
O
O
+ CH3 CCl
Benzene
Acetyl
chloride
AlCl3
CCH3
+ HCl
Acetophenone
9-43
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Friedel-Crafts Acylation
• the electrophile is an acylium cation
O
••
••
R- C Cl
••
+
Cl
A l- Cl
Cl
O
R- C
+
••
Cl
-
Cl A l Cl
••
Cl
O
R- C+ A lCl 4 An ion pair
containing
an acylium ion
9-44
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Other Alkylations
• Carbocations are generated by
• treatment of an alkene with a protic acid, most
commonly H2SO4, H3PO4, or HF/BF3
+
Benzene
CH3 CH= CH2
Propene
(Propylene)
H3 PO4
CH( CH3 ) 2
Isopropylbenzene
(Cumene)
9-45
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Other Alkylations
• by treating an alkene with a Lewis acid
A lCl 3
+
Benzene
Cyclohexene
Phenylcyclohexane
• and by treating an alcohol with H2SO4 or H3PO4
H 3 P O4
C( CH3 ) 3 + H2 O
+ ( CH3 ) 3 COH
Benzene
tert-Butyl
alcohol
tert-Butylbenzene
9-46
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Disubstitution
• Existing groups on benzene ring influence further
substitution in both orientation and rate
• Orientation:
• certain substituents direct preferentially to ortho & para
positions; others direct preferentially to meta positions
• substituents are classified as either
ortho-para directing or meta directing
9-47
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Disubstitution
• Rate:
• certain substituents cause the rate of a second
substitution to be greater than that for benzene itself;
others cause the rate to be lower
• substituents are classified as
• activating toward further substitution, or
• deactivating
9-48
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Disubstitution
• -OCH3 is ortho-para directing
OCH 3
Br 2
CH 3 CO2 H
Anisole
OCH 3
OCH 3
Br
+
o-Bromoanisole
(4%)
+
HBr
Br
p-Bromoanisole
(96%)
9-49
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Disubstitution
• -NO2 is meta directing
NO2
+ HNO 3
H2 SO4
NO2
NO2
NO2
NO2
Nitrobenzene
+
+
NO2
m-Dinitrobenzene
(93%)
o-Dinitrobenzene
NO2
p-Dinitrobenzene
Less than 7% combined
9-50
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
Strongly
activating
Moderately
activating
Weakly
activating
••
NH 2
••
NHR
O
••
NR2
NHCR
••
••
••
OH
O
O
••
••
••
••
••
••
OCAr
OCR
R
••
Br
••
••
I
••
Cl
••
••
••
••
••
••
Weakly
deactivating ••F
OR
Impotance in Directing
Ortho-para Directing
9 Disubstitution
••
9-51
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
O
O
O
O
CR
COH COR
Moderately CH
O
deactivating O
SOH C N
CNH 2
O
Strongly
deactivating NO2
NH 3
+
CF3
CCl3
Impotance in Directing
Meta Directing
9 Disubstitution
9-52
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Disubstitution
• From the information in Table 9.2, we can make
these generalizations
• alkyl groups, phenyl groups, and all groups in which
the atom bonded to the ring has an unshared pair of
electrons are ortho-para directing. All other groups are
meta directing
• all ortho-para directing groups except the halogens are
activating toward further substitution. The halogens
are weakly deactivating
9-53
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Disubstitution
CH 3
CO2 H
HNO 3
K 2 Cr 2 O7
H 2 SO 4
H 2 SO 4
CH 3
NO2
NO2
p-Nitrobenzoic
acid
CO2 H
CO 2 H
K 2 Cr 2 O7
HNO 3
H 2 SO 4
H 2 SO 4
NO2
m-Nitrobenzoic
acid
9-54
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Theory of Directing Effects
• The rate of EAS is limited by the slowest step in
the mechanism
• for almost every EAS, the rate-limiting step is attack of
E+ on the aromatic ring to form a resonance-stabilized
cation intermediate
• the more stable this cation intermediate, the faster the
rate-limiting step and the faster the overall reaction
9-55
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Theory of Directing Effects
• For ortho-para directors, ortho-para attack forms
a more stable cation than meta attack
• ortho-para products are formed faster than meta
products
• For meta directors, meta attack forms a more
stable cation than ortho-para attack
• meta products are formed faster than ortho-para
products
9-56
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Theory of Directing Effects
• -OCH3; assume meta attack
OCH 3
+ NO 2
+
OCH 3
+
H
NO 2
(a)
slow
OCH 3
OCH 3
OCH 3
+
H
H
NO 2
(b)
+ NO 2
(c)
fast
-H +
NO 2
9-57
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Theory of Directing Effects
• -OCH3: assume ortho-para attack
9-58
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Theory of Directing Effects
• -NO2; assume meta attack
NO 2
+ NO 2
+
NO 2
NO 2
+
H
NO 2
(a)
slow
NO 2
NO 2
+
H
H
NO 2
(b)
+ NO 2
(c)
fast
-H +
NO 2
9-59
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9 Theory of Directing Effects
• -NO2: assume ortho-para attack
9-60
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
9
Aromatic
Compounds
End Chapter 9
9-61
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.