Reactivity of Benzene

Benzenes 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 CCC bond angles is 120 Each C is sp2 and has a p orbital perpendicular to the plane of the six-membered ring
2

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.
3

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)

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.

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
Benzenes 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 C followed by

neutralization with acid replaces the SO3H group with an OH Example is the synthesis of p-cresol

AROMATICALKYLATION
The FriedelCrafts Reaction

Aluminum chloride

promotes the formation of the carbocation

Wheland intermediate

forms

AROMATIC ALKYLATION
Many ways of CARBOCATION FORMATION

Cl CH3 CH CH3 + AlCl3

_ CH3 + C Cl AlCl3 H3C H

_ H2C CH CH3 HF F + H3C CH CH3

OH H3C CH CH3

BF3

+ BF3 H O H3C CH CH3

_ + H3C CH CH3 + HOBF3

=>

AROMATIC ALKYLATION
Formation of Alkyl Benzene
CH3 +C H CH3 + H CH(CH3)2 H

F H
+

B OH F

CH3 CH + CH3 F F

HF B OH

CH(CH3)2 H

=>

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

FORMYLATION
Gatterman-Koch

Formyl chloride is unstable. Use a high

pressure mixture of CO, HCl, and catalyst. Product is benzaldehyde.

O CO + HCl
O + C+ H

H C

Cl

AlCl3/CuCl
O C H

_ + H C O AlCl4

HCl

=>

SUMMARY

Soal tantangan
Reaksi elektrofilik aromatik 10.27 sampai 10 29 10.48

SUBSTITUENT EFFECTS IN ELECTROFILIC AROMATIC SUBTITUTION

ACTIVATOR
DEACTIVATOR
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 paradirecting 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 s 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 s 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 of Activators

=>

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 of Activators

=>

Deactivating MetaDirecting 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 Substitution on Nitrobenzene

=>

Para Substitution on Nitrobenzene

=>

Meta Substitution on 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 benzena 10.30 10.34

Efek dari substituen 10.50

Pengarahan orto para 10.31 10.32 10.33

TRISUBSTITUTED BENZENES
Br OH Cl CH2CH3 NO2 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 orthodisubstituted compound

Soal tantangan
Substitusi ke 3 10.36 10.37 10.38 10.39 10.49

10.51 10.52

Jalur Reaksi mana dipilih?

Reaksi mana dipilih?

NUCLEOPHILIC AROMATIC SUBSTITUTION

NUCLEOPHILIC AROMATIC 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 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 Addition-Elimination: The SNAr Mechanism

Nucleophilic substitution can occur on benzene rings when strong electron-withdrawing groups are ortho or para to the halogen atom The more electronwithdrawing groups on the ring, the lower the temperature required for the reaction to proceed

addition-elimination mechanism
A Meisenheimer complex, which is a delocalized carbanion, is an intermediate

The carbanion is stabilized by electron-withdrawing groups in the ortho and para positions

Addition-Elimination Mechanism

=>

NUCLEOPHILIC AROMATIC SUBSTITUTION

Aryl halides with

electron-withdrawing substituents ortho and para react with nucleophiles Form addition intermediate (Meisenheimer complex) that is stabilized by electronwithdrawal Halide ion is lost to give aromatic ring

Soal tantangan
Substitusi nukleofilik 10.14

Sintesis 10.45 10.46 10.47

Sintesis 10.53 10.54 10.55 10.56 10.57 10.58