Chapter 17 Aromatic Reactions - San Diego Miramar Collegefaculty.sdmiramar.edu/choeger/Chapter 17...

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Chapter 17Reactions of

Aromatic Compounds

Chapter 17: Aromatics 2-Reactions Slide 17-2

Electrophilic Aromatic Substitution

Electrophile substitutes for a hydrogen on the benzene ring.

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Mechanism

Step 1: Attack on the electrophile forms the sigma complex.

=>

Step 2: Loss of a proton gives the substitution product.


Bromination of Benzene

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

Br

HBr+

Br Br FeBr3 Br Br FeBr3

+ -

Br Br FeBr3

H

H

H

H

H

H

H

H

H

H

HH

Br+ + FeBr4

_+ -

=>

3


Comparison with Alkenes

• Cyclohexene adds Br2, ΔH = -121 kJ• Addition to benzene is endothermic, not normally seen.• Substitution of Br for H retains aromaticity, ΔH = -45 kJ.• Formation of sigma complex is rate-limiting.

=>


Energy Diagramfor Bromination

=>

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Chlorinationand Iodination

• Chlorination is similar to bromination. Use AlCl3 as theLewis 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 ionelectrophile.

NO2+ then forms a sigma complex with benzene,

loses H+ to form nitrobenzene.

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Sulfonation

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

S

O

O O

S

O

O O

S

O

O O

S

O

O O

+ + +

_

_ _


Desulfonation• All steps are reversible, so sulfonic acid group can be

removed by heating in dilute sulfuric acid.• This process is used to place deuterium in place of hydrogen

on benzene ring.

Benzene-d6

D

D

D

D

D

D

D2SO4/D2O

large excess

H

H

H

H

H

H

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Nitration of Toluene

• Toluene reacts 25 times faster than benzene. The methyl group isan activating group.

• The product mix contains mostly ortho and para substitutedmolecules.

=>


Sigma Complex

Intermediate is morestable if nitrationoccurs at the orthoor para position.

=>

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Energy Diagram

=>


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 sigmacomplex by resonance.

OCH3

H

NO2

+

OCH3

H

NO2

+

=>

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Substitution on Anisole

=>


The Amino Group

Aniline, like anisole, reacts with bromine water (without acatalyst) to yield the tribromide. Sodium bicarbonate isadded to neutralize the HBr that’s also formed.

=>

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Summary ofActivators

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Deactivating Meta-Directing Substituents

• Electrophilic substitution reactions for nitrobenzene are100,000 times slower than for benzene.

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

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

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Ortho Substitution on Nitrobenzene

=>


Para Substitution on Nitrobenzene

=>

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Meta Substitution on Nitrobenzene

=>


Energy Diagram

=>

12


Structure of Meta-Directing Deactivators

• The atom attached to the aromatic ring will have a partialpositive charge.

• Electron density is withdrawn inductively along the sigmabond, so the ring is less electron-rich than benzene.

=>


Summary of Deactivators

=>

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More Deactivators

=>


Halobenzenes

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

• Since halogens are very electronegative, they withdrawelectron density from the ring inductively along the sigmabond.

• But halogens have lone pairs of electrons that can stabilizethe sigma complex by resonance.=>

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Sigma Complex for Bromobenzene

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

=>

No bromonium ionpossible with meta attack.


Energy Diagram

=>

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Summary of Directing Effects

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Multiple Substituents

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

OCH3

O2N

SO3

H2SO4

OCH3

O2N

SO3H

OCH3

O2N

SO3H

+

=>

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Friedel-Crafts Alkylation

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

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

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

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Examples 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

_

=>

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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

=>

+

-


Limitations of Friedel-Crafts

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

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

• The alkylbenzene product is more reactive than benzene, sopolyalkylation occurs. =>

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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

C

O

R

+

H

C

H

O

R

+

Cl AlCl3

_C

O

R +

HCl

AlCl3

=>

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Clemmensen Reduction

Acylbenzenes can be converted to alkylbenzenes by treatmentwith aqueous HCl and amalgamated zinc. Works for non-aromatic ketones as well; rearrangements can occur.

+ CH3CH2C

O

Cl1) AlCl3

2) H2O

C

O

CH2CH3Zn(Hg)

aq. HCl

CH2CH2CH3

=>


Wolff-Kishner Reduction

Acylbenzenes can be also converted to alkylbenzenes by treatmentwith aqueous NH2NH2 and hydroxide (mechanism next chapter).Works for non-aromatic ketones as well.

O H H

NH2NH2

KOHaq. ethylene glycol

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Gatterman-Koch Formylation

• Formyl chloride is unstable. Use a high pressure mixture ofCO, HCl, and catalyst.

• Product is benzaldehyde.

CO + HCl H C

O

ClAlCl3/CuCl

H C O+

AlCl4

_

C

O

H

+C

O

H

+ HCl+


Nucleophilic Aromatic Substitution

• A nucleophile replaces a leaving group on the aromaticring.

• Electron-withdrawing substituents activate the ring fornucleophilic substitution.

=>

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Examples of Nucleophilic Substitution

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Addition-Elimination Mechanism

=>

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Benzyne Mechanism• Reactant is halobenzene with no

electron-withdrawing groups on the ring.• Use a very strong base like NaNH2.

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Benzyne Intermediate

=>

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Chlorination of Benzene• Addition to the benzene ring may

occur with high heat and pressure(or light).

• The first Cl2 addition is difficult, but the next 2 moles addrapidly.

• The product, benzene hexachloride, is an insecticide.

=>


Catalytic Hydrogenation

• Elevated heat and pressure is required.• Possible catalysts: Pt, Pd, Ni, Ru, Rh.• Reduction cannot be stopped at an intermediate stage.

=>

CH3

CH3Ru, 100°C

1000 psi3H2,

CH3

CH3

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Birch Reduction: Regiospecific

• A carbon bearing an e--withdrawing group is reduced.

• A carbon bearing an e--releasing group is not reduced.

C

O

OH Na, NH3

CH3CH2OH

C

O

O

H

_

OCH3 Li, NH3

(CH3)3COH, THF

OCH3

=>


Birch Mechanism

=>

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Side-Chain Oxidation

Alkylbenzenes are oxidized to benzoic acid by hot KMnO4 orNa2Cr2O7/H2SO4.

CH(CH3)2

CH CH2

KMnO4, OH-

H2O, heat

COO

COO_

_


Side-Chain Halogenation

• Benzylic position is the most reactive.• Chlorination is not as selective as bromination, results in

mixtures.• Br2 reacts only at the benzylic position.

CHCH2CH3

Br

h!Br2,

CH2CH2CH3

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SN1 Reactions

• Benzylic carbocations are resonance-stabilized, easily formed.• Benzyl halides (even primary!) undergo SN1 reactions.

CH2BrCH3CH2OH, heat

CH2OCH2CH3

=>


SN2 Reactions

• Benzylic halides are 100 times more reactive than primaryhalides via SN2.

• Transition state is stabilized by ring.

=>

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Reactions of Phenols

• Some reactions like aliphatic alcohols:phenol + carboxylic acid → esterphenol + aq. NaOH → phenoxide ion

• Oxidation to quinones: 1,4-diketones.

OH

CH3

Na2Cr2O7, H2SO4

CH3

O

O

=>


Quinones

• Hydroquinone is used as a developer for film. It reacts withlight-sensitized AgBr grains, converting it to black Ag.

• Coenzyme Q is an oxidizing agent found in the mitochondriaof cells. =>

OH

OH

+ 2 AgBr

O

O

+ 2 Ag + 2 HBr

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Electrophilic Substitution of Phenols

• Phenols and phenoxides are highly reactive.• Only a weak catalyst (HF) required for Friedel-Crafts reaction.• Tribromination occurs without catalyst.• Even reacts with CO2.

O_

CO2, OH-

O

C

O

O_

_

H+

OH

C

O

OH

salicylic acid

=>


End of Chapter 17

Homework: 44, 46, 47, 49, 52, 53,56, 57, 61, 63, 64, 67

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