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General
Organic ChemistryTwo credits
Second Semester 2009
King Saud bin Abdulaziz University for Health Science
Reference Book: Organic Chemistry: A Brief Course, by Robert C. Atkins and Francis A. CareyThird Edition
Instructor: Rabih O. Al-Kaysi, PhD.
Chapter 6Chapter 6
AROMATIC COMPOUNDSAROMATIC COMPOUNDS
Lecture 11
Reactions of Arenes:Reactions of Arenes:
A PreviewA Preview
1. Some reactions involve the ring.1. Some reactions involve the ring.
2. In other reactions the ring is a substituent.2. In other reactions the ring is a substituent.
a) Reductiona) Reduction
Catalytic hydrogenation Catalytic hydrogenation
Birch reduction Birch reduction
b) Electrophilic aromatic substitutionb) Electrophilic aromatic substitution
c) Nucleophilic aromatic substitutionc) Nucleophilic aromatic substitution
1. Reactions involving the ring1. Reactions involving the ring
2. The ring as a substituent 2. The ring as a substituent
catalytic catalytic hydrogenationhydrogenation
Birch reductionBirch reduction HH
HH
HH HH
HHHH
HH HH
HH
HH HH
HH
HH HH
Reduction of Benzene RingsReduction of Benzene RingsReduction of Benzene RingsReduction of Benzene Rings
HHHH
HHHH HH
HH
HH
HHHH
HH HH
HH
The Birch ReductionThe Birch Reduction
(80%)(80%)
HH
HH
HH HH
HHHH
HH HH
HH
HH HH
HH
HH HH
Na, NHNa, NH33
CHCH33OHOH
Birch Reduction of BenzeneBirch Reduction of BenzeneBirch Reduction of BenzeneBirch Reduction of Benzene
Product is non-conjugated diene.Product is non-conjugated diene.
Reaction stops here. There is no further reduction.Reaction stops here. There is no further reduction.
Reaction is not hydrogenation. HReaction is not hydrogenation. H22 is not involved in any way. is not involved in any way.
Oxidation of AlkylbenzenesOxidation of Alkylbenzenes
Site of Oxidation is Benzylic CarbonSite of Oxidation is Benzylic CarbonSite of Oxidation is Benzylic CarbonSite of Oxidation is Benzylic Carbon CHCH33 CHCH22RR CHRCHR22
oror
oror
COHCOH
OONaNa22CrCr22OO77
HH22SOSO44
HH22OO
heatheat
ExampleExampleExampleExample
NaNa22CrCr22OO77
HH22SOSO44
HH22OO
heatheat
CH(CHCH(CH33))22
CHCH33
(45%)(45%)
COHCOH
OO COHCOH
OO
•hydrogenation
•halogenation
•addition of hydrogen halides
Addition Reactions of Addition Reactions of AlkenylbenzenesAlkenylbenzenes
HydrogenationHydrogenation
HH22
PtPt
(92%)(92%)
BrBr
CC
CHCH33
CHCHCHCH33
BrBr
CHCHCHCH22CHCH33
CHCH33
HalogenationHalogenation CHCH22CHCH
BrBr22
CHCH22CHCH
BrBrBrBr
(82%)(82%)
Addition of Hydrogen HalidesAddition of Hydrogen Halides
HClHCl
(75-84%)(75-84%)
ClCl
Polymerization of Polymerization of StyreneStyrene
Polymerization of StyrenePolymerization of Styrene
HH22CC CHCHCC66HH55
CHCH22 CHCH
CC66HH55
CHCH22 CHCH
CC66HH55
CHCH22 CHCH
CC66HH55
polystyrenepolystyrene
Reactions of Arenes:Reactions of Arenes:Electrophilic Aromatic SubstitutionElectrophilic Aromatic Substitution
HH
EE
++ EE YY ++ HH YY++ ––
HH
EE
++ EE YY ++ HH YY++ ––
Electrophilic aromatic substitutions include:Electrophilic aromatic substitutions include:Electrophilic aromatic substitutions include:Electrophilic aromatic substitutions include:
NitrationNitration
SulfonationSulfonation
HalogenationHalogenation
Friedel-Crafts AlkylationFriedel-Crafts Alkylation
Friedel-Crafts AcylationFriedel-Crafts Acylation
HH
Nitration of BenzeneNitration of BenzeneNitration of BenzeneNitration of Benzene
++ ++ HH22OO
HH22SOSO44
HOHONONO22
NONO22
NitrobenzeneNitrobenzene(95%)(95%)
HH
Sulfonation of BenzeneSulfonation of BenzeneSulfonation of BenzeneSulfonation of Benzene
++ ++ HH22OO
heatheatHOHOSOSO22OHOH
SOSO22OHOH
Benzenesulfonic acidBenzenesulfonic acid(100%)(100%)
HH
Halogenation of BenzeneHalogenation of BenzeneHalogenation of BenzeneHalogenation of Benzene
++ ++ HHBrBr
FeBrFeBr33
BrBr22
BrBr22
BromobenzeneBromobenzene(65-75%)(65-75%)
HH
Friedel-Crafts Alkylation of BenzeneFriedel-Crafts Alkylation of BenzeneFriedel-Crafts Alkylation of BenzeneFriedel-Crafts Alkylation of Benzene
++ ++ HHClCl
AlClAlCl33
C(CHC(CH33))33
terttert-Butylbenzene-Butylbenzene(60%)(60%)
(CH(CH33))33CCClCl
HH
Friedel-Crafts Acylation of BenzeneFriedel-Crafts Acylation of BenzeneFriedel-Crafts Acylation of BenzeneFriedel-Crafts Acylation of Benzene
++ ++ HHClCl
AlClAlCl33
1-Phenyl-1-propanone1-Phenyl-1-propanone(88%)(88%)
OO
CHCH33CHCH22CCClCl
CCHCCH22CHCH33
OO
Mechanistic PrinciplesMechanistic Principlesofof
Electrophilic Aromatic SubstitutionElectrophilic Aromatic Substitution
Step 1: attack of electrophileStep 1: attack of electrophileon on -electron system of aromatic ring-electron system of aromatic ring
Step 1: attack of electrophileStep 1: attack of electrophileon on -electron system of aromatic ring-electron system of aromatic ring
HH HH
HH HHHH HH
EE++ HH HH
HHHH
HH HH EE
++
highly endothermichighly endothermic
carbocation is allylic, but not aromaticcarbocation is allylic, but not aromatic
Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate
Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate
HH HH
HH EEHH HH
HH++ HH HH
HHHH
HH HH EE
++
highly exothermichighly exothermic
this step restores aromaticity of ringthis step restores aromaticity of ring
Nitration of BenzeneNitration of Benzene
HH
Nitration of BenzeneNitration of BenzeneNitration of BenzeneNitration of Benzene
++ ++ HH22OO
HH22SOSO44
HOHONONO22
NONO22
Electrophile isElectrophile isnitronium ion nitronium ion
OO NN OO••••
++
•••••••• ••••
Step 1: attack of nitronium cationStep 1: attack of nitronium cationon on -electron system of aromatic ring-electron system of aromatic ring
Step 1: attack of nitronium cationStep 1: attack of nitronium cationon on -electron system of aromatic ring-electron system of aromatic ring
HH HH
HH HHHH HH
NONO22++
HH HH
HHHH
HH HH NONO22
++
Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate
Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate
HH HH
HH NONO22
HH HH
HH++ HH HH
HHHH
HH HH NONO22
++
Halogenation of BenzeneHalogenation of Benzene
HH
Halogenation of BenzeneHalogenation of BenzeneHalogenation of BenzeneHalogenation of Benzene
++ ++ HHBrBr
FeBrFeBr33
BrBr22
BrBr22
Electrophile is a Lewis acid-Lewis baseElectrophile is a Lewis acid-Lewis basecomplex between FeBrcomplex between FeBr33 and Br and Br22..
The BrThe Br22-FeBr-FeBr33 Complex ComplexThe BrThe Br22-FeBr-FeBr33 Complex Complex
++••••BrBr BrBr•••••••• ••••
•••• ••••
Lewis baseLewis base Lewis acidLewis acid
FeBrFeBr33
BrBr BrBr•••••••• ••••
•••• ••••FeBrFeBr33
––++
ComplexComplex
The BrThe Br22-FeBr-FeBr33 complex is more electrophilic complex is more electrophilic
than Brthan Br22 alone. alone.
Step 1: attack of BrStep 1: attack of Br22-FeBr-FeBr33 complex complex
on on -electron system of aromatic ring-electron system of aromatic ring
Step 1: attack of BrStep 1: attack of Br22-FeBr-FeBr33 complex complex
on on -electron system of aromatic ring-electron system of aromatic ring HH HH
HH HHHH HH
HH HH
HHHH
HH HH BrBr
++
BrBr BrBr FeBrFeBr33
––++
+ FeBr+ FeBr44––
Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate
Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate
HH HH
HH BrBrHH HH
HH++ HH HH
HHHH
HH HH BrBr
++
Rate and Regioselectivity in Rate and Regioselectivity in Electrophilic Aromatic SubstitutionElectrophilic Aromatic Substitution
A substituent already present on the ring A substituent already present on the ring can affect both the can affect both the raterate and and regioselectivityregioselectivityof electrophilic aromatic substitution.of electrophilic aromatic substitution.
ActivatingActivating substituents increase the rate substituents increase the rate of EAS compared to that of benzene.of EAS compared to that of benzene.
DeactivatingDeactivating substituents decrease substituents decrease the rate of EAS compared to benzene. the rate of EAS compared to benzene.
Effect on RateEffect on RateEffect on RateEffect on Rate
Toluene undergoes nitration Toluene undergoes nitration 20-25 times faster than 20-25 times faster than benzene.benzene.
A methyl group is an A methyl group is an activatingactivating substituent. substituent.
Methyl GroupMethyl GroupMethyl GroupMethyl Group CHCH33
(Trifluoromethyl)benzene (Trifluoromethyl)benzene undergoes nitration 40,000 undergoes nitration 40,000 times more slowly than benzene .times more slowly than benzene .
A trifluoromethyl group is aA trifluoromethyl group is adeactivatingdeactivating substituent. substituent.
Trifluoromethyl GroupTrifluoromethyl GroupTrifluoromethyl GroupTrifluoromethyl Group CFCF33
Ortho-para directors Ortho-para directors direct an incoming direct an incoming electrophile to positions ortho and/or electrophile to positions ortho and/or para to themselves.para to themselves.
Meta directors Meta directors direct an incoming direct an incoming electrophile to positions meta to electrophile to positions meta to themselves.themselves.
Effect on RegioselectivityEffect on RegioselectivityEffect on RegioselectivityEffect on Regioselectivity
Nitration of TolueneNitration of TolueneNitration of TolueneNitration of Toluene CHCH33
HNOHNO33
aceticaceticanhydrideanhydride
CHCH33
NONO22
CHCH33
NONO22
CHCH33
NONO22
++ ++
34%34%3%3%63%63%
oo- and - and pp-nitrotoluene together comprise 97% -nitrotoluene together comprise 97% of the productof the product
a methyl group is an ortho-para directora methyl group is an ortho-para director
Nitration of (Trifluoromethyl)benzeneNitration of (Trifluoromethyl)benzeneNitration of (Trifluoromethyl)benzeneNitration of (Trifluoromethyl)benzene CFCF33 CFCF33
NONO22
CFCF33
NONO22
CFCF33
NONO22
++ ++
3%3%91%91%6%6%
mm-nitro(trifluoromethyl)benzene comprises -nitro(trifluoromethyl)benzene comprises 91% of the product91% of the product
a trifluoromethyl group is a meta directora trifluoromethyl group is a meta director
HNOHNO33
HH22SOSO44
Rate and RegioselectivityRate and Regioselectivityin thein the
Nitration of TolueneNitration of Toluene
Carbocation Stability Controls RegioselectivityCarbocation Stability Controls RegioselectivityCarbocation Stability Controls RegioselectivityCarbocation Stability Controls Regioselectivity ++
HH
HH
HH
CHCH33
HH
HH
NONO22
++
HH
HH
HH
HH
HH
NONO22
CHCH33 ++
HH
HH
HH
HH
HH
NONO22
CHCH33
gives orthogives ortho gives paragives para gives metagives meta
Carbocation Stability Controls RegioselectivityCarbocation Stability Controls RegioselectivityCarbocation Stability Controls RegioselectivityCarbocation Stability Controls Regioselectivity ++
HH
HH
HH
CHCH33
HH
HH
NONO22
++
HH
HH
HH
HH
HH
NONO22
CHCH33 ++
HH
HH
HH
HH
HH
NONO22
CHCH33
gives orthogives ortho gives paragives para gives metagives meta
more stablemore stable less stableless stable
ortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Toluene ++
HH
HH
HH
CHCH33
HH
HH
NONO22
ortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Toluene ++
HH
HH
HH
CHCH33
HH
HH
NONO22
HH
HH
HH
CHCH33
HH
HH
NONO22
++
ortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Toluene ++
HH
HH
HH
CHCH33
HH
HH
NONO22
HH
HH
HH
CHCH33
HH
HH
NONO22
HH
HH
HH
CHCH33
HH
HH
NONO22
++
++
this resonance this resonance
form is a form is a tertiary tertiary
carbocationcarbocation
ortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Toluene ++
HH
HH
HH
CHCH33
HH
HH
NONO22
the rate-determining intermediate in the orthothe rate-determining intermediate in the orthonitration of toluene has tertiary carbocation nitration of toluene has tertiary carbocation charactercharacter
HH
HH
HH
CHCH33
HH
HH
NONO22
HH
HH
HH
CHCH33
HH
HH
NONO22
++
++
para Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluene ++
HH
HH
HH
HH
HH
NONO22
CHCH33
para Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluene ++
HH
HH
HH
HH
HH
NONO22
CHCH33 HH
HH
HH
HH
HH
NONO22
CHCH33
++
this resonance this resonance form is a tertiary form is a tertiary
carbocationcarbocation
para Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluene ++
HH
HH
HH
HH
HH
NONO22
CHCH33 HH
HH
HH
HH
HH
NONO22
CHCH33
HH
HH
HH
HH
HH
NONO22
CHCH33
++
++
this resonance this resonance form is a tertiary form is a tertiary
carbocationcarbocation
para Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluene ++
HH
HH
HH
HH
HH
NONO22
CHCH33 HH
HH
HH
HH
HH
NONO22
CHCH33
HH
HH
HH
HH
HH
NONO22
CHCH33
++
++
the rate-determining intermediate in the parathe rate-determining intermediate in the paranitration of toluene has tertiary carbocation nitration of toluene has tertiary carbocation charactercharacter
meta Nitration of Toluenemeta Nitration of Toluenemeta Nitration of Toluenemeta Nitration of Toluene ++
HH
HH
HH
HH
HH
NONO22
CHCH33
meta Nitration of Toluenemeta Nitration of Toluenemeta Nitration of Toluenemeta Nitration of Toluene ++
HH
HH
HH
HH
HH
NONO22
CHCH33 HH
HH
HH
HH
HH
NONO22
CHCH33
++
meta Nitration of Toluenemeta Nitration of Toluenemeta Nitration of Toluenemeta Nitration of Toluene ++
HH
HH
HH
HH
HH
NONO22
CHCH33 HH
HH
HH
HH
HH
NONO22
CHCH33
HH
HH
HH
HH
HH
NONO22
CHCH33
++
++
all the resonance forms of the rate-all the resonance forms of the rate-determining intermediate in the meta nitration determining intermediate in the meta nitration of toluene have their positive charge on a of toluene have their positive charge on a secondary carbonsecondary carbon
Nitration of Toluene: InterpretationNitration of Toluene: InterpretationNitration of Toluene: InterpretationNitration of Toluene: Interpretation
• The rate-determining intermediates for ortho and The rate-determining intermediates for ortho and para nitration each have a resonance form that is para nitration each have a resonance form that is a tertiary carbocation. All of the resonance forms a tertiary carbocation. All of the resonance forms for the rate-determining intermediate in meta for the rate-determining intermediate in meta nitration are secondary carbocations.nitration are secondary carbocations.
• Tertiary carbocations, being more stable, are Tertiary carbocations, being more stable, are formed faster than secondary ones. Therefore, formed faster than secondary ones. Therefore, the intermediates for attack at the ortho and para the intermediates for attack at the ortho and para positions are formed faster than the intermediate positions are formed faster than the intermediate for attack at the meta position. This explains why for attack at the meta position. This explains why the major products are the major products are o- o- and and pp-nitrotoluene.-nitrotoluene.
Nitration of Toluene: Partial Rate FactorsNitration of Toluene: Partial Rate FactorsNitration of Toluene: Partial Rate FactorsNitration of Toluene: Partial Rate Factors
• The experimentally determined reaction rate can The experimentally determined reaction rate can be combined with the ortho/meta/para distribution be combined with the ortho/meta/para distribution to give to give partial rate factors partial rate factors for substitution at the for substitution at the various ring positions.various ring positions.
• Expressed as a numerical value, a partial rate Expressed as a numerical value, a partial rate factor tells you by how much the rate of factor tells you by how much the rate of substitution at a particular position is faster (or substitution at a particular position is faster (or slower) than at a single position of benzene.slower) than at a single position of benzene.
Rate and RegioselectivityRate and Regioselectivityin thein the
Nitration of (Trifluoromethyl)benzeneNitration of (Trifluoromethyl)benzene
A Key PointA Key PointA Key PointA Key Point
CC ++HH33CC CC ++FF33CC
A methyl group is electron-donating and A methyl group is electron-donating and stabilizes a carbocation.stabilizes a carbocation.
Because F is so electronegative, a CFBecause F is so electronegative, a CF33 group group
destabilizes a carbocation.destabilizes a carbocation.
Carbocation Stability Controls RegioselectivityCarbocation Stability Controls RegioselectivityCarbocation Stability Controls RegioselectivityCarbocation Stability Controls Regioselectivity ++
HH
HH
HH
CFCF33
HH
HH
NONO22
++
HH
HH
HH
HH
HH
NONO22
CFCF33 ++
HH
HH
HH
HH
HH
NONO22
CFCF33
gives orthogives ortho gives paragives para gives metagives meta
Carbocation Stability Controls RegioselectivityCarbocation Stability Controls RegioselectivityCarbocation Stability Controls RegioselectivityCarbocation Stability Controls Regioselectivity ++
HH
HH
HH
CFCF33
HH
HH
NONO22
++
HH
HH
HH
HH
HH
NONO22
CFCF33 ++
HH
HH
HH
HH
HH
NONO22
CFCF33
gives orthogives ortho gives paragives para gives metagives meta
less stableless stable more stablemore stable
Substituent Effects in ElectrophilicSubstituent Effects in ElectrophilicAromatic Substitution:Aromatic Substitution:Activating SubstituentsActivating Substituents
Table 12.2Table 12.2Table 12.2Table 12.2
Very strongly activatingVery strongly activating
Strongly activatingStrongly activating
ActivatingActivating
Standard of comparison is HStandard of comparison is H
DeactivatingDeactivating
Strongly deactivatingStrongly deactivating
Very strongly deactivatingVery strongly deactivating
Classification of Substituents in Electrophilic Classification of Substituents in Electrophilic Aromatic Substitution ReactionsAromatic Substitution Reactions
1. All activating substituents are 1. All activating substituents are ortho-para directors.ortho-para directors.
2. Halogen substituents are slightly 2. Halogen substituents are slightly deactivating but ortho-para directing.deactivating but ortho-para directing.
3. Strongly deactivating substituents are 3. Strongly deactivating substituents are meta directors.meta directors.
GeneralizationsGeneralizationsGeneralizationsGeneralizations
are ortho-para directing and activatingare ortho-para directing and activating ERGERG
ERGs include —R, —Ar, and —C=CERGs include —R, —Ar, and —C=C
Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)
are ortho-para directing and strongly activatingare ortho-para directing and strongly activating ERGERG
ERGs such as —OH, and —OR areERGs such as —OH, and —OR arestrongly activatingstrongly activating
Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)
occurs about 1000 times faster than nitration occurs about 1000 times faster than nitration of benzeneof benzene OHOH
HNOHNO33
OHOH
NONO22
OHOH
NONO22
++
44%44% 56%56%
Nitration of PhenolNitration of PhenolNitration of PhenolNitration of Phenol
FeBrFeBr33 catalyst not necessary catalyst not necessary OCHOCH33
BrBr22
OCHOCH33
BrBr
90%90%
aceticaceticacidacid
Bromination of AnisoleBromination of AnisoleBromination of AnisoleBromination of Anisole
ERGs with a lone pair on the atom directlyERGs with a lone pair on the atom directlyattached to the ring are ortho-para directingattached to the ring are ortho-para directing
and strongly activatingand strongly activating
ERGERG
Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)Electron-Releasing Groups (ERGs)
••••
All of these are ortho-para directingAll of these are ortho-para directingand strongly to very strongly activatingand strongly to very strongly activating
ExamplesExamplesExamplesExamples
ERG = ERG = •••• ••••OH OH ••••
OR OR ••••••••
OCR OCR ••••••••
OO
•••• NHNH22 NHCR NHCR ••••
OO
••••NHR NHR •••• NRNR22
