1

Reactivity of Benzene

2

Benzene’s Unusual Structure

All its C-C bonds are the same length: 139 pm — between single (154 pm) and double (134 pm) bonds, which means that electron density in all six C-C bonds is identical

Structure is planar, hexagonal, thus C–C–C bond angles is 120° Each C is sp2 and has a p orbital perpendicular to the plane of

the six-membered ring

3

Stability of Benzene

Benzene is a cyclic compound that consists of six carbon atoms bonded together by σ bonds and a set of delocalized π bonds.

All the electrons associated with those π bonds delocalize over all six carbons.

Delocalized electrons in a cyclic conjugated system have a dramatic effect on the stability of the molecule.

4

HEATS OF HYDROGENATION AS INDICATORS OF STABILITY

Therefore C6H6 has about 150 kJ more “stability” than an isolated set of three double bonds (See Figure 15-2)

5

Stability of BenzeneIn fact, this stability makes aromatic molecules so unreactive that they do not follow the expected reaction pathways that their structures suggest they should.

Electrophilic Aromatic Substitution

Substitution Reactions of Benzene

Electrophilic aromatic substitution replaces a proton on benzene with another electrophile

Bromination of Aromatic Rings

FeBr3 is added as a catalyst to polarize the bromine reagent

INTERMEDIATE IN BROMINATION

Benzene’s electrons participate as a Lewis base (act as a nucleophile) toward Br2 (in a complex with FeBr3)

This reaction forms a cationic addition intermediate

The intermediate is not aromatic and therefore high in energy.

FORMATION OF PRODUCT

The cationic addition intermediate transfers a proton to FeBr4

- (from Br- and FeBr3)

This restores aromaticity (in contrast with addition in alkenes)

AROMATIC CHLORINATION/IODINATION

Chlorine and iodine (but not fluorine, which is too reactive) can produce aromatic substitution with the addition of other reagents to promote the reaction

Chlorination requires FeCl3 Iodine must be oxidized to form a more powerful I+

species (with Cu+ or peroxide)

AROMATIC NITRATION The combination of nitric acid and sulfuric acid

produces NO2+ (nitronium ion)

The reaction with benzene produces nitrobenzene

AROMATIC SULFONATION Substitution of H by SO3 (sulfonation) Reaction with a mixture of sulfuric acid and SO3 Reactive species is sulfur trioxide or its conjugate acid Reaction occurs via Wheland intermediate and is

reversible

Alkali Fusion of Aromatic Sulfonic Acids

Sulfonic acids are useful as intermediates Heating with NaOH at 300 ºC followed by

neutralization with acid replaces the SO3H group with an OH

Example is the synthesis of p-cresol

AROMATICALKYLATION The Friedel–Crafts Reaction

Aluminum chloride promotes the formation of the carbocation

Wheland intermediate forms

Many ways of CARBOCATION FORMATION

CH3 CH CH3

Cl

+ AlCl3

CH3C

H3C H

Cl AlCl3+ _

H2C CH CH3

HFH3C CH CH3

F+

_

H3C CH CH3

OHBF3

H3C CH CH3

OH BF3+

H3C CH CH3+

+ HOBF3

_

=>

AROMATIC ALKYLATION

Formation of Alkyl Benzene

C

CH3

CH3

H+

H

H

CH(CH3)2+

H

H

CH(CH3)2

B

F

F

F

OHCH

CH3

CH3

+

HF

BF

OHF

=>

+

-

AROMATIC ALKYLATION

CARBOCATION REARRANGEMENTS During Alkylation

Similar to those that occur during electrophilic additions to alkenes

Can involve H or alkyl shifts

Carbocation Rearrangements During Alkylation

Similar to those that occur during electrophilic additions to alkenes

Can involve H or alkyl shifts

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

FRIEDEL-CRAFTS ACYLATION

Similar to alkylation Reactive electrophile: resonance-stabilized acyl cation An acyl cation does not rearrange

FORMYLATIONGatterman-Koch

Formyl chloride is unstable. Use a 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

+ C

O

H+ HCl+

=>

SUMMARY

Reaksi elektrofilik aromatik10.27 sampai 10 2910.48

Soal tantangan

SUBSTITUENT EFFECTS IN ELECTROFILIC AROMATIC

SUBTITUTION

DEACTIVATOR

ACTIVATOR

Meta-Directing

Ortho- and Para-Directing

Inductive effects

Resonance effect

EFFECT OF SUBSTITUENT on Friedel-Crafts Alkylation

Alkylation will not work with rings containing an amino group substituent or a strongly electron-withdrawing group

On the other hand multiple alkylations occur and become a major products

SUBSTITUENT EFFECTS IN AROMATIC RINGS

Substituents can cause a compound to be (much) more or (much) less reactive than benzene

Substituents affect the orientation of the reaction – the positional relationship is controlled ortho- and para-directing activators, ortho- and para-directing

deactivators, and meta-directing deactivators

ORIGINS OF SUBSTITUENT EFFECTS

An interplay of inductive effects and resonance effects

Inductive effect - withdrawal or donation of electrons through a bond

Resonance effect - withdrawal or donation of electrons through a bond due to the overlap of a p orbital on the substituent with a p orbital on the aromatic ring

RESONANSI, PERGESERAN ELEKTRON, STRUKTUR RESONANSI (penyumbang utama, penyumbang tambahan), STABILISASI RESONANSI (bab 1 hal.70-77)

32

Inductive Effects Controlled by electronegativity and the polarity of

bonds in functional groups Halogens, C=O, CN, and NO2 withdraw electrons

through bond connected to ring Alkyl groups donate electrons

Resonance Effects – Electron Withdrawal

C=O, CN, NO2 substituents withdraw electrons from the aromatic ring by resonance

electrons flow from the rings to the substituents

Resonance Effects – Electron Donation

Halogen, OH, alkoxyl (OR), and amino substituents donate electrons

electrons flow from the substituents to the ring Effect is greatest at ortho and para

An Explanation of Substituent Effects

Activating groups donate electrons to the ring, stabilizing the Wheland intermediate (carbocation)

Deactivating groups withdraw electrons from the ring, destabilizing the Wheland intermediate

Ortho- and Para-Directing Activators: Alkyl Groups Alkyl groups activate/direct further substitution to positions

ortho and para to themselves Alkyl group is most effective in the ortho and para positions

Energy Diagram

=>

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

Summary ofActivators

=>

Ortho- and Para-Directing Deactivators: Halogens Electron-withdrawing inductive effect outweighs

weaker electron-donating resonance effect Resonance effect is only at the ortho and para

positions, stabilizing carbocation intermediate

Summary ofActivators

=>

Deactivating Meta-Directing Substituents Electrophilic substitution reactions for

nitrobenzene are 100,000 times slower than for benzene.

The product mix contains mostly the meta isomer, only small amounts of the ortho and para isomers.

Meta-directors deactivate all positions on the ring, but the meta position is less deactivated. =>

Ortho Substitutionon Nitrobenzene

=>

Para Substitution on Nitrobenzene

=>

Meta Substitutionon Nitrobenzene

=>

Energy Diagram

=>

Meta-Directing Deactivators

Inductive and resonance effects reinforce each other Ortho and para intermediates destabilized by

deactivation from carbocation intermediate Resonance cannot produce stabilization

Summary of Deactivators

=>

More Deactivators

=>

Summary Table: Effect of Substituents in Aromatic Substitution

Summary of Directing Effects

=>

Soal tantangan

Pengaktifan cincin benzena10.3010.34

Pengarahan orto para10.3110.3210.33

Efek dari substituen10.50

TRISUBSTITUTED BENZENES

Br

CH2CH3

NO2

OH

Cl

Br

Trisubstituted Benzenes: Additivity of Effects If the directing effects of the two groups are the

same, the result is additive

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

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

Soal tantangan

Substitusi ke 310.3610.3710.3810.3910.49

10.5110.52

Jalur Reaksi mana dipilih?

Reaksi mana dipilih?

NUCLEOPHILIC AROMATIC

SUBSTITUTION

NUCLEOPHILICAROMATIC SUBSTITUTION

A nucleophile replaces a leaving group on the aromatic ring.

Electron-withdrawing substituents activate the ring for nucleophilic substitution.

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

SN2 reaction also doesn’t 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 substitution can 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 temperature required for the reaction to proceed

Nucleophilic Aromatic Substitution by Addition-Elimination: The SNAr Mechanism

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

Addition-EliminationMechanism

=>

NUCLEOPHILIC AROMATIC SUBSTITUTION

Aryl halides with electron-withdrawing substituents ortho and para react with nucleophiles

Form addition intermediate (Meisenheimer complex) that is stabilized by electron-withdrawal

Halide ion is lost to give aromatic ring

Soal tantangan

Substitusi nukleofilik10.14

Sintesis10.4510.4610.47

Sintesis10.5310.5410.5510.5610.5710.58