Lecture 11 - AROMATIC COMPOUNDS

transcript

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

Reduction of Benzene RingsReduction of Benzene RingsReduction of Benzene RingsReduction of Benzene Rings

HHHH HH

The Birch ReductionThe Birch Reduction

(80%)(80%)

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

COHCOH

OONaNa22CrCr22OO77

HH22SOSO44

HH22OO

heatheat

ExampleExampleExampleExample

NaNa22CrCr22OO77

HH22SOSO44

HH22OO

heatheat

CH(CHCH(CH33))22

CHCH33

(45%)(45%)

COHCOH

OO COHCOH

•hydrogenation

•halogenation

•addition of hydrogen halides

Addition Reactions of Addition Reactions of AlkenylbenzenesAlkenylbenzenes

HydrogenationHydrogenation

(92%)(92%)

CHCH33

CHCHCHCH33

CHCHCHCH22CHCH33

CHCH33

HalogenationHalogenation CHCH22CHCH

BrBr22

CHCH22CHCH

BrBrBrBr

(82%)(82%)

Addition of Hydrogen HalidesAddition of Hydrogen Halides

HClHCl

(75-84%)(75-84%)

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

++ 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

Nitration of BenzeneNitration of BenzeneNitration of BenzeneNitration of Benzene

++ ++ HH22OO

HH22SOSO44

HOHONONO22

NONO22

NitrobenzeneNitrobenzene(95%)(95%)

Sulfonation of BenzeneSulfonation of BenzeneSulfonation of BenzeneSulfonation of Benzene

++ ++ HH22OO

heatheatHOHOSOSO22OHOH

SOSO22OHOH

Benzenesulfonic acidBenzenesulfonic acid(100%)(100%)

Halogenation of BenzeneHalogenation of BenzeneHalogenation of BenzeneHalogenation of Benzene

++ ++ HHBrBr

FeBrFeBr33

BrBr22

BromobenzeneBromobenzene(65-75%)(65-75%)

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

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%)

CHCH33CHCH22CCClCl

CCHCCH22CHCH33

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

HH HHHH HH

EE++ HH HH

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

HH EEHH HH

HH++ HH HH

HH HH EE

highly exothermichighly exothermic

this step restores aromaticity of ringthis step restores aromaticity of ring

Nitration of BenzeneNitration of Benzene

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

HH HHHH HH

NONO22++

HH HH NONO22

HH NONO22

HH++ HH HH

HH HH NONO22

Halogenation of BenzeneHalogenation of Benzene

Halogenation of BenzeneHalogenation of BenzeneHalogenation of BenzeneHalogenation of Benzene

++ ++ HHBrBr

FeBrFeBr33

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 BrBr

BrBr BrBr FeBrFeBr33

––++

+ FeBr+ FeBr44––

HH BrBrHH HH

HH++ HH HH

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 ++

CHCH33

NONO22

CHCH33 ++

NONO22

CHCH33

gives orthogives ortho gives paragives para gives metagives meta

CHCH33

NONO22

CHCH33 ++

NONO22

CHCH33

more stablemore stable less stableless stable

ortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Tolueneortho Nitration of Toluene ++

CHCH33

NONO22

CHCH33

NONO22

CHCH33

NONO22

CHCH33

NONO22

CHCH33

NONO22

CHCH33

NONO22

this resonance this resonance

form is a form is a tertiary tertiary

carbocationcarbocation

CHCH33

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

CHCH33

NONO22

CHCH33

NONO22

para Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluenepara Nitration of Toluene ++

NONO22

CHCH33

NONO22

CHCH33 HH

NONO22

CHCH33

this resonance this resonance form is a tertiary form is a tertiary

NONO22

CHCH33 HH

NONO22

CHCH33

NONO22

CHCH33

this resonance this resonance form is a tertiary form is a tertiary

NONO22

CHCH33 HH

NONO22

CHCH33

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 ++

NONO22

CHCH33

NONO22

CHCH33 HH

NONO22

CHCH33

NONO22

CHCH33 HH

NONO22

CHCH33

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.

CFCF33

NONO22

CFCF33 ++

NONO22

CFCF33

NONO22

CFCF33 ++

NONO22

CFCF33

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

occurs about 1000 times faster than nitration occurs about 1000 times faster than nitration of benzeneof benzene OHOH

HNOHNO33

NONO22

44%44% 56%56%

Nitration of PhenolNitration of PhenolNitration of PhenolNitration of Phenol

FeBrFeBr33 catalyst not necessary catalyst not necessary OCHOCH33

BrBr22

OCHOCH33

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

••••

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 ••••••••

•••• NHNH22 NHCR NHCR ••••

••••NHR NHR •••• NRNR22

Lecture 11 - AROMATIC COMPOUNDS

Documents