CHEMISTRY OF BENZENE:ELECTROPHILIC AROMATIC SUBSTITUTION

Dr. Sheppard

CHEM 2412

Summer 2015

Klein (2nd ed.) sections: 19.1, 19.2, 19.3, 19.4, 19.5, 19.6,

18.6, 19.7, 19.8, 19.9, 19.10,

19.11, 19.12

Benzene Reactivity• Unsaturated, but doesn’t behave like alkene

• Alkenes:

• Benzene:

• Reaction is called electrophilic aromatic substitution

Reactions of Aromatic Compounds

I. Electrophilic aromatic substitution mechanism

II. Halogenation

III. Sulfonation

IV. Nitration

V. Friedel-Crafts Alkylation and Acylation

VI. Reactions of Benzene Substituents

VII. EAS on Substituted Benzenes

VIII. Synthesis

Electrophilic Aromatic Substitution• Aromatic ring (nucleophile) + electrophile

Electrophilic Aromatic Substitution• Mechanism:

Halogenation• Reagents

• X2

• Br2 or Cl2• F2 too reactive, I2 needs additional reagents

• FeX3 or AlX3

• Catalyst• Makes X2 more electrophilic

• Example: brominationBr2

FeBr3

Br

X2

FeX3

X

Halogenation Mechanism

Energy Diagram• Aromatic (substitution) product is more stable than

product from addition across double bond

• See benzene worksheet questions 1-19

• SO3 and H2SO4 = “fuming sulfuric acid”

• Electrophile = SO3 or HSO3+

• Sulfonic acid can be converted into phenol• Not covered in Klein

Sulfonation SO3

H2SO4

SO3H

SO3H

1. NaOH,

2. H3O+

OH

• Electrophile = nitronium ion (NO2+)

Nitration HNO3

H2SO4

NO2

• Nitro group can be reduced to amine• Reagents:

• 1. SnCl2, Zn, or Fe and H+

• H2, metal catalyst• Will also reduce C≡C, C=C, but not benzene

Nitration HNO3

H2SO4

NO2

Friedel-Crafts Alkylation• New carbon-carbon bond between benzene and R group• Example:

• Catalyst makes RX a better electrophile (~R+)

RX

AlX3 or FeX3

R

Limitations to Friedel-Crafts Alkylation

1. RX structure• X = Cl, Br, I• R = alkyl (not aryl or vinylic)

Limitations to Friedel-Crafts Alkylation

2. Reaction fails on benzenes substituted with electron-withdrawing groups (EWGs)

• These groups remove electron-density from the benzene ring (make the nucleophile less nucleophilic)

3. Reaction fails on benzenes substituted with amino groups

• These groups can react with the catalyst• These groups can become protonated and form –NH3

+ (EWG)

Limitations to Friedel-Crafts Alkylation

4. Multiple substitution can occur• Polyalkylation

Limitations to Friedel-Crafts Alkylation

5. Rearrangements can occur• Electrophile is ~R+, so can rearrange to make a more stable R+

Example• Draw the product of the F-C alkylation reaction of

benzene with 1-chloro-2-methylpropane (using the appropriate catalyst)

• New carbon-carbon bond between benzene and acyl group• Example:

• Reaction still does not work with EWG or amine• No polyalkylation

• Reaction only occurs once because product contains EWG

• No rearrangements• Acyl cation stabilized by resonance

Friedel-Crafts Acylation

Example

• Aryl ketones can be reduced to form alkyl benzenes

• This alkyl benzene cannot be made from F-C alkylation• Rearrangement

• Reducing agents• H2, metal catalyst

• Will also reduce C=C, C≡C, NO2

• Zn(Hg), HCl (Clemmensen reduction)

AlCl3

O

Cl

O

+ HCl

O

[H]

Reactions of Benzene Substituents• Already seen in this chapter:

1. ─NO2 → ─NH2

2. ─SO3H → ─OH

3. ─C(O)R → ─CH2R

• Additional reactions:4. Oxidation with KMnO4 or H2CrO4

• Additional reactions:5. Halogenation

• Forms alkyl halide, which can undergo further substitution or elimination• Reaction occurs at benzylic position

• Most stable radical intermediate

Reactions of Benzene Substituents

Br

NBS or Br2

h or peroxides

Summary of Reactions

7

8

2 6

1

X

R NO2 NH2

R

O

9

R

5SO3H OH

4

3

CO2H

Propose a synthesis for the following compound, using benzene as the starting material.

CH2 C N

Is it possible to synthesize propylbenzene using a Friedel-Crafts alkylation? Explain.

Propose an alternate synthesis for propylbenzene from benzene.

The following conversion requires more than one step. Show reagents and experimental conditions necessary to bring about this conversion.

OH