Electrophilic Substitution Reaction of Pyrrole

• Substitution is preferred at 2-position

• Presence of bulky group at 1-position, directs the electrophile at 3-position

• Presence of electron-releasing group directs the electrophile at 5-position

• Present of electron-withdrawing group at 2-position directs the electrophile at 4 ang 5 positions.

• Reagents:

• Nitration: HNO3/acetic anhydride

• Halogenation (polychclorination): Cl2/SO2Cl2

• Acylation: acetic anhydride

• Alkylation (polyalkylation): CH3I

Electrophilic Substitution of Furans

• Substitution at 2 and 5 positions

• If 2 and 5 are occupied substitution occurs at 3 and 4 positions

Reagents:

Nitration: HNO3/acetic anhydride

Sulfonation: SO3/pyridine

Halogenation: dioxane/Br2

Alkylation: RCH=CH2/H3PO4

Acylation: aceticanhydride/H3PO4 or BF3

Electrophilic Substitution of Benzothiophene

• Substitution at 2-position is preferred

• Reagents:

• Nitration: aceticanhydride/HNO3

• Sulfonation: H2SO4/30oC

• Halogenation (mixture); Cl2/-30oC

• Bromination: NBS

• Alkylation: CH3CH=CH2/H3PO4

• Acylation: CH3COCl/SnCl4

Polymerization Reaction under acidic condition

Reactions of Pyrrole

Reactions of Pyrrole

1 Nitration-HNO3/H2SO4 – not suitable, extensive decomposition

Reagent: HNO3/acetic anhydride: product, 2 (major), 3(minor)- substituted

2. chlorination: Cl2/SO2Cl2 = polychlorination

3. Acylation: Acetic anhydride (100-150oC)- 2- (major), 2,5 (minor)- substituted

Acyhalide (no friedel craft reagent, promote polymerization

4. Hydroxymethylation: Mannic Reaction

N

CH2=O

(CH3)2NH/dil H+ N

N

CH3I

N

N+ I

KCN

N

CN

N

COOH

mannich base

N

R'

R

O

H+

N

OH

H

+-H2O

N

R'

R

H

+

N

NH

R'R

N

H

H+

N

R'R

N

NH

NH

HN

HN

R'

R

R'R

RR' R

R'

Cyclic- if R, R' = CH3Cyclic if R=H, R'=benzeneLinear if R', R= H

airPorphyrin

Reactions with Electrophiles

Indole

- Presence of benzene deactivates the pyrrole moiety

- Substitution at 3-position preferred over 2-position(benzoid structure disrupt the aromatic ring

- The presence of electron-withdrawing substituents at the position-1,2 or -3 of the pyrrole ring deactivates the pyrrole ring of indole towards electropilic attack and the substitution occurs in the benzene ring in the positional reactivity: 6>4>5>7. The electron-releasing substituents on the benzene ring exert normal directional influence on the electrophilic substitution (ortho to the substituent)

• Electrophilic Substitution of Benzofuran

• Substitution is expected to be at the beta position as in indole, but instead electrophilic substitution occurrs at the alpha position because of the most powerful alpha-directing effect of the oxygen ring atom. The transition state (3H-cation) resulting from the electrophilic attack at the beta position is less stable than that resulting from the attack at the alpha position because the ring oxygen being highly electronegative accomodates positive charge less readily than the ring carbon, thus providing insufficient stabilization to the 3H-cation.

• -the presence of electron-releasing group at the 2-position, directs the electrophile to the 3-position• -the presence of electron-releasing group at the 3-position, directs the electrophile at the 2- posiition• -the presence of electron-withdrawing group deactivates the furan moiety, and substitution occurs at

the 5 and in some cases at the 7-position.• The presence of electron-releasing group in the benzene ring directs the electrophile at the ortho- or

para to the substituent.• -the presence of electron-withdrawing group in the benzene ring directs the electrophile at the 2-

position of the furan moiety.

• Electrophilic Substitution of Benzothophene• -presence of benzene deactivates the reactivity of thiophene moiety• -substitution occurs preferentially at the beta position like indole, but alpha position is also obtained.• -if the thiophene is substituted with electron-withdrawing group or if the benzene is substituted with

electron-releasing group, substitution occurs at the benzene moiety.• -the presence of electron-releasing group at 2-position directs the electrophile at 3-position.• -the presence of electron-releasing group at 3- position directs the electrophile at 2-position• -the presence of elecron-releasing group in the benzene ring directs the electrophile ortho-or –para to

the substituent