2013 Lect5 Elect_aromatik Substitution

5/28/2018 2013 Lect5 Elect_aromatik Substitution

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1

Reactivity of Benzene


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2

Benzenes Unusual Structure

All its C-C bonds arethe same length: 139 pm between

single (154 pm) and double (134 pm) bonds, which means thatelectron density in all six C-C bonds isidentical

Structure is planar, hexagonal, thus CCC bond angles is 120

Each C issp2 and hasaporbital perpendicular to the plane ofthe six-membered ring


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3

Stability of Benzene

Benzene is a cyclic compound that consists of six carbon atoms

bonded together by bonds and a set of delocalized bonds.

All the electrons associated with those bonds delocalize over all six

carbons.

Delocalized electrons in a cyclic conjugated system have a dramatic

effect on the stability of the molecule.


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4

HEATS OF HYDROGENATION AS INDICATORS OF STABILITY

Therefore C6H6has about 150 kJ more stability than an

isolated set of three double bonds (See Figure 15-2)


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5

Stability of Benzene

In fact, this stability makes aromatic molecules so unreactive that they

do not follow the expected reaction pathways that their structures

suggest they should.


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Electrophilic Aromatic

Substitution


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Substitution Reactions of Benzene

Electrophilic aromatic substitution replaces a

proton on benzene with another electrophile


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Bromination of Aromatic Rings

FeBr3is added asa catalyst to polarizethe brominereagent


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INTERMEDIATE IN BROMINATION

Benzenes electrons participate asa Lewis base (actasa nucleophile) towardBr2(in a complex with FeBr3)

This reaction formsa cationic addition intermediate

The intermediate is notaromatic andtherefore high in energy.


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FORMATION OF PRODUCT

The cationic addition intermediate

transfersa proton to FeBr4-(from

Br-and FeBr3)

This restores aromaticity (in

contrast with addition in alkenes)


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AROMATIC CHLORINATION/IODINATION

Chlorine and iodine (but not fluorine, which is tooreactive) can producearomatic substitution with theaddition ofother reagents to promotethe reaction

Chlorination requiresFeCl3

Iodine must be oxidized to forma more powerful I+

species (with Cu+ or peroxide)


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AROMATIC NITRATION

The combination of nitric acid and sulfuric acidproduces NO2+(nitronium ion)

The reaction with benzene producesnitrobenzene


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AROMATIC SULFONATION

Substitution of H by SO3(sulfonation)

Reaction with a mixture of sulfuric acid and SO3

Reactive species issulfur trioxide or its conjugate acid

Reaction occurs viaWheland intermediate andisreversible


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Alkali Fusion of Aromatic Sulfonic Acids

Sulfonic acids are useful as intermediates

Heating withNaOH at 300 C followed by

neutralization with acid replacesthe SO3H group with

an OH

Exampleis the synthesis ofp-cresol


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AROMATICALKYLATION

The FriedelCrafts Reaction

Aluminum chloridepromotestheformation of thecarbocation

Wheland intermediateforms


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Many ways of

CARBOCATION FORMATION

CH3 CH CH3

Cl

+ AlCl3

CH3C

H3C H

Cl AlCl3+ _

H2C CH CH3HF

H3C CH CH3

F+

_

H3C CH CH3

OHBF3

H3C CH CH3

OH BF3+

H3C CH CH3+

+ HOBF3

_

=>

AROMATIC ALKYLATION


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Formation of Alkyl Benzene

C

CH3

CH3

H+

H

H

CH(CH3)2+

H

H

CH(CH3)2

B

F

F

F

OH

CH

CH3

CH3

+

HF

BF

OHF

=>

+

-

AROMATIC ALKYLATION


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CARBOCATION REARRANGEMENTS

During Alkylation

Similar to those that occurduring electrophilicadditions to alkenes

Can involveH or alkyl shifts


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Carbocation Rearrangements

During Alkylation

Similar to those thatoccurduring electrophilicadditions to alkenes

Can involveH or alkyl shifts


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ACYLATION OF AROMATIC RINGS

Reaction of an acid chloride (RCOCl) and an

aromatic ring in the presence of AlCl3 introduces acyl

group, COR

Benzene with acetyl chloride yields acetophenone


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FRIEDEL-CRAFTS ACYLATION

Similar to alkylation

Reactive electrophile: resonance-stabilized acyl cation

An acyl cation does not rearrange


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FORMYLATIONGatterman-Koch

Formyl chloride is unstable. Usea high

pressure mixture of CO, HCl, and catalyst.

Product is benzaldehyde.

CO + HCl H C

O

ClAlCl3/CuCl

H C O+

AlCl4

_

C

O

H

+ CO

H+ HCl+

=>


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SUMMARY


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Reaksi elektrofilik aromatik

10.27 sampai 10 29

10.48

Soal tantangan


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SUBSTITUENT EFFECTSIN ELECTROFILIC AROMATIC

SUBTITUTION

DEACTIVATOR

ACTIVATOR

Meta-Directing

Ortho- and Para-Directing

Inductive effects

Resonance effect


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EFFECT OF SUBSTITUENT

on Friedel-Crafts Alkylation

Alkylation will not work withrings containing an aminogroup substituent or a strongly electron-withdrawinggroup


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On the other hand multiple alkylations occur

and become a major products


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SUBSTITUENT EFFECTS IN AROMATIC RINGS

Substituents can causea compound to be (much) more or

(much) less reactive than benzene Substituentsaffect the orientation of the reactionthe

positional relationship is controlled

ortho- and para-directing activators, ortho- and para-

directing deactivators, and meta-directing deactivators


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ORIGINS OF SUBSTITUENT EFFECTS

An interplay of inductive effectsand resonance

effects

Inductive effect- withdrawal or donation of electrons

through a sbond Resonance effect- withdrawal or donation of

electrons througha bond due tothe overlap of ap

orbital on the substituent with aporbital on the

aromatic ring

RESONANSI, PERGESERAN ELEKTRON, STRUKTUR RESONANSI

(penyumbang utama, penyumbang tambahan), STABILISASI

RESONANSI (bab 1 hal.70-77)


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32
http://en.wikipedia.org/wiki/File:Ortho_para_directing_substituents.JPG


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Inductive Effects

Controlled byelectronegativity and the polarity ofbonds in functional groups

Halogens, C=O, CN, and NO2withdrawelectrons

throughsbond connectedto ring

Alkyl groups donateelectrons


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Resonance EffectsElectron

Withdrawal

C=O, CN, NO2substituents withdrawelectrons from

the aromatic ring by resonance

electrons flow fromthe rings tothe substituents


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Resonance EffectsElectron Donation

Halogen, OH, alkoxyl (OR), and amino substituentsdonate electrons

electrons flow fromthe substituents tothe ring

Effectisgreatest at ortho and para


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An Explanation of Substituent Effects

Activating groupsdonate electronstothe ring,stabilizingtheWheland

intermediate(carbocation)

Deactivatinggroups withdrawelectronsfrom the

ring, destabilizingthe Whelandintermediate


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Ortho- and Para-Directing Activators:

Alkyl Groups

Alkyl groups activate/directfurther substitution topositions ortho and para to themselves

Alkyl groupis most effective in the ortho and parapositions


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Energy Diagram

=>


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Ortho- and Para-Directing Activators:

OH and NH2

Alkoxyl, and amino groups have a strong, electron-donating resonance effect

Most pronounced at the ortho and para positions


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Summary of

Activators

=>


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Ortho- and Para-Directing

Deactivators: Halogens

Electron-withdrawing inductive effect outweighsweaker electron-donating resonance effect

Resonance effect is only at the ortho and parapositions, stabilizing carbocation intermediate


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Summary of

Activators

=>


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Deactivating Meta-

Directing Substituents

Electrophilic substitution reactions fornitrobenzene are 100,000 times slower thanfor benzene.

The product mix contains mostly the metaisomer, only small amounts of the orthoandpara isomers.

Meta-directors deactivate all positions on the

ring, but the meta position is less deactivated.=>


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Ortho Substitution

on Nitrobenzene

=>

b i i


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Para Substitution

on Nitrobenzene

=>

S b i i


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Meta Substitution

on Nitrobenzene

=>


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Energy Diagram

=>


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Meta-Directing Deactivators

Inductive and resonance effects reinforce each other

Ortho and para intermediates destabilized bydeactivation from carbocation intermediate

Resonance cannot produce stabilization


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Summary of Deactivators

=>


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More Deactivators

=>


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Summary Table:

Effect of Substituents in Aromatic Substitution

S f


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Summary of

Directing Effects

=>


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Soal tantangan

Pengaktifan cincin benzena

10.30

10.34

Pengarahan orto para

10.31

10.32

10.33

Efek dari substituen

10.50


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TRISUBSTITUTED

BENZENESBr

CH2CH3

NO2

OH

Cl

Br

T i b i d B Addi i i f


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Trisubstituted Benzenes: Additivity of

Effects

If the directing effects of the two groups are the

same, the result is additive


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Substituents with Opposite Effects

If the directing effects of two groups oppose each

other, the more powerful activating group decides the

principal outcome

Often gives mixtures of products

M t Di b tit t d C d A


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Meta-Disubstituted Compounds Are

Unreactive

The reaction site is too hindered To make aromatic rings with three adjacent

substituents, it is best to start with an ortho-disubstituted compound


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Soal tantangan

Substitusi ke 310.36

10.37

10.38

10.39

10.49

10.51

10.52


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Jalur Reaksi mana dipilih?


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Reaksi mana dipilih?


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NUCLEOPHILIC

AROMATICSUBSTITUTION


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NUCLEOPHILIC

AROMATIC SUBSTITUTIONA nucleophile replaces a leaving group on the

aromatic ring.

Electron-withdrawing substituents activate thering for nucleophilic substitution.

Ar l Halides and N cleophilic


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Aryl Halides and Nucleophilic

Aromatic Substitution

Simple aryl and vinyl halides do not undergo nucleophilic substitution

Back-side attack required for SN2 reaction is blocked in

aryl halides


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SN2 reaction also doesnt occur in aryl (and vinyl

halides) because the carbon-halide bond is

shorter and stronger than in alkyl halides

Bonds to sp2-hybridized carbons are shorter, and

therefore stronger, than to

sp3-hybridized carbons

Resonance gives the carbon-halogen bond some

double bond character

Nucleophilic Aromatic Substitution by


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Nucleophilic substitutioncan occur on benzene

rings when strong

electron-withdrawing

groups are ortho or para

to the halogen atom

The more electron-

withdrawing groups

on the ring, the lower

the temperaturerequired for the

reaction to proceed

p y

Addition-Elimination: The SNAr Mechanism

ddi i li i i h i


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The carbanion is stabilized by electron-withdrawing groups

in the ortho and para positions

addition-elimination mechanism

A Meisenheimer complex, which is a delocalized carbanion, is an intermediate

Addi i Eli i i


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Addition-Elimination

Mechanism

=>

NUCLEOPHILIC AROMATIC


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NUCLEOPHILIC AROMATIC

SUBSTITUTION

Aryl halides withelectron-withdrawingsubstituents ortho andpara react withnucleophiles

Form additionintermediate(Meisenheimercomplex) that isstabilized by electron-

withdrawal Halide ion is lost to

give aromatic ring


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Soal tantangan

Substitusi nukleofilik

10.14

Sintesis

10.45

10.46

10.47

Sintesis

10.53

10.54

10.55

10.5610.57

10.58

Documents

2013 Lect5 Elect_aromatik Substitution