The document summarizes electrophilic substitution reactions of various aromatic heterocyclic compounds. For pyrrole, substitution prefers the 2-position and reagents include nitric acid, chlorine, and acetic anhydride. For furan, substitution occurs at the 2 and 5-positions. For benzothiophene, substitution prefers the 2-position with reagents like nitric acid and chlorine. Polymerization can occur under acidic conditions for pyrrole. Indole substitution prefers the 3-position and is deactivated by electron-withdrawing groups. For benzofuran, substitution occurs at the alpha position rather than beta due to oxygen's directing effect.

51. 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

52. 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

53. 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

55. Polymerization Reaction under acidic condition

56. 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

88. 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)

89. 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