Electrophilic Attack

Electrophilic Aromatic Substitution

Electrophile substitutes for a hydrogen on the benzene ring.

Mechanism

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Bromination of Benzene• Requires a stronger electrophile than Br2.• Use a strong Lewis acid catalyst, FeBr3.

Br Br FeBr3 Br Br FeBr3

Br Br FeBr3

H

H

H

H

H

H

H

H

H

H

H H

Br+ + FeBr4

_

Br

HBr+

Energy Diagram for Bromination

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Chlorination and Iodination

• Chlorination is similar to bromination. Use AlCl3 as the Lewis acid catalyst.

• Iodination requires an acidic oxidizing agent, like nitric acid, which oxidizes the iodine to an iodonium ion.

H+ HNO3 I21/2 I+ NO2 H2O+ ++ +

Nitration of Benzene

Use sulfuric acid with nitric acid to form the nitronium ion electrophile.

H O N

O

O

H O S O H

O

O+ HSO4

_H O N

OH

O+

H O N

OH

O+

H2O + N

O

O

+NO2

+ then forms asigma complex withbenzene, loses H+ toform nitrobenzene. =>

Sulfonation

Sulfur trioxide, SO3, in fuming sulfuric acid is the electrophile.

S

O

O OS

O

O OS

O

O OS

O

O O

+ + +

_

_ _

S

O

O O

H

SO

OOH

+

_S

HOO

O

benzenesulfonic acid

Nitration of Toluene• Toluene reacts 25 times faster than benzene.

The methyl group is an activator.• The product mix contains mostly ortho and

para substituted molecules.

Sigma Complex

Intermediate is more stable if nitration occurs at the ortho or para position.

Energy Diagram

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Friedel-Crafts Alkylation

• Synthesis of alkyl benzenes from alkyl halides and a Lewis acid, usually AlCl3.

• Reactions of alkyl halide with Lewis acid produces a carbocation which is the electrophile.

• Other sources of carbocations: alkenes + HF or alcohols + BF3.

Examples of Carbocation Formation

CH3 CH CH3

Cl

+ AlCl3

CH3C

H3C HCl AlCl3

+ _

H2C CH CH3HF

H3C CH CH3

F+

_

H3C CH CH3

OHBF3

H3C CH CH3

OH BF3+

H3C CH CH3+ + HOBF3

_

=>

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

+

-

Limitations of Friedel-Crafts

• Reaction fails if benzene has a substituent that is more deactivating than halogen.

• Carbocations rearrange. Reaction of benzene with n-propyl chloride and AlCl3 produces isopropylbenzene.

• The alkylbenzene product is more reactive than benzene, so polyalkylation occurs.

Friedel-Crafts Acylation

• Acyl chloride is used in place of alkyl chloride.• The acylium ion intermediate is resonance

stabilized and does not rearrange like a carbocation.

• The product is a phenyl ketone that is less reactive than benzene.

Mechanism of Acylation

R C

O

Cl AlCl3 R C

O

AlCl3Cl+ _

R C

O

AlCl3Cl+ _

AlCl4 +_ +

R C O R C O+

C

O

R

+

H

C

H

O

R

+Cl AlCl3

_C

O

R +HCl

AlCl3

Clemmensen Reduction

Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc.

+ CH3CH2C

O

Cl1) AlCl3

2) H2O

C

O

CH2CH3Zn(Hg)

aq. HCl

CH2CH2CH3

Gatterman-Koch Formylation

• 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+

Activating, O-, P-Directing Substituents

• Alkyl groups stabilize the sigma complex by induction, donating electron density through the sigma bond.

• Substituents with a lone pair of electrons stabilize the sigma complex by resonance.

OCH3

HNO2

+

OCH3

HNO2

+

The Amino Group

Aniline reacts with bromine water (without a catalyst) to yield the tribromide. Sodium bicarbonate is added to neutralize the HBr that’s also formed.

NH2

Br23

H2O, NaHCO3

NH2

Br

Br

Br

=>

Summary of Activators

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 Substitution on Nitrobenzene

Para Substitution on Nitrobenzene

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Meta Substitution on Nitrobenzene

Energy Diagram

Structure of Meta-Directing Deactivators• The atom attached to the aromatic ring

will have a partial positive charge.• Electron density is withdrawn

inductively along the sigma bond, so the ring is less electron-rich than benzene.

Summary of Deactivators

More Deactivators

Halobenzenes

• Halogens are deactivating toward electrophilic substitution, but are ortho, para-directing!

• Since halogens are very electronegative, they withdraw electron density from the ring inductively along the sigma bond.

• But halogens have lone pairs of electrons that can stabilize the sigma complex by resonance.

Sigma Complex for Bromobenzene

Br

E+

BrH

E

(+)

(+)(+)

Ortho attack

+ Br

E+

Br

H E

+

(+)

(+)(+)

Para attack

Ortho and para attacks produce a bromonium ionand other resonance structures.

Meta attack

Br

E+

Br

H

H

E

+

(+)

(+)No bromonium ion possible with meta attack.

Energy Diagram

Summary of Directing Effects

Multiple Substituents

The most strongly activating substituent will determine the position of the next substitution. May have mixtures.

OCH3

O2N

SO3

H2SO4

OCH3

O2N

SO3H

OCH3

O2N

SO3H

+

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II. Electrophilic Addition

“Loose” p electrons are nucleophilic (Lewis bases), react with electrophiles (Lewis acids).

C C

Y Z

C C

Y

C C

Y ZZ

+ -

nucleophile

electrophile

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C C

H XH X+C C

II. Electrophilic AdditionA. Addition of hydrogen halides

(X = Cl, Br, I)

Reactivity: HI > HBr > HCl >> HF (stronger acid = better electrophile)

-+

X

C C

H X

C C

HH X

C CRLS fast

Br

HBr

IHI

39

II. Electrophilic AdditionA. Addition of hydrogen halides

1. Markovnikov’s rule

In the addition of HX to an alkene, the H goes to the carbon with more H’s.

CH3 CH CH2 CH3 CH

Br

CH3CH3 CH2 CH2 Brbut not

HBr

HI

HCl

HBr

HI

Question 6-2. Draw the products. Click on the arrow to check answers.

Check Answer

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II. Electrophilic AdditionA. Addition of hydrogen halides

1. Markovnikov’s rule

In the addition of HX to an alkene, the H goes to the carbon with more H’s.

CH3 CH CH2 CH3 CH

Br

CH3CH3 CH2 CH2 Brbut not

HBr

HI

HCl

HBr

HI

Answer 6-2.

I

Cl

BrI

I

and

41

II. Electrophilic Addition

A. Addition of hydrogen halides

2. mechanism

Mechanistic interpretation of Markovnikov’s rule: The reaction proceeds through the more stable carbocation intermediate.

CH3 CH CH2

CH3 CH CH3

CH3 CH2 CH2

H Br Br Br

Br Br

2º carbocationmore stable

1º carbocationless stable

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II. Electrophilic AdditionA. Addition of hydrogen halides

2. mechanism

+ HBr

Br

Brlower Ea faster rate offormation

Br

Br