Organic Chemistry

900 CHAPTER 21 More About Amines • Heterocyclic Compounds

The relative reactivities of the five-membered-ring heterocycles are reflected in the

Lewis acid required to catalyze a Friedel–Crafts acylation reaction (Section 15.13).

Benzene requires a relatively strong Lewis acid. Thiophene is more reactive

than benzene, so it can undergo a Friedel–Crafts reaction using a weaker Lewis

acid. An even weaker Lewis acid, can be used when the substrate is furan. Pyr-

role is so reactive that an anhydride is used instead of a more reactive acyl chloride,

and no catalyst is necessary.

The resonance hybrid of pyrrole indicates that there is a partial positive charge on

the nitrogen. Therefore, pyrrole is protonated on C-2 rather than on nitrogen. Remem-

ber, a proton is an electrophile and, like other electrophiles, attaches to the C-2 posi-

tion of pyrrole.

Pyrrole is unstable in strongly acidic solutions because once protonated, it can readily

polymerize.

Pyrrole is more acidic than the analogous saturated amine

because the nitrogen in pyrrole is hybridized and is, therefore,

more electronegative than the nitrogen of a saturated amine (Table 21.1). Pyrrole’s

acidity also is increased as a result of its conjugate base being stabilized by electron

sp^3

1 pKa= ' 362 , sp^2

1 pKa = ' 172

N

H

N

H

N

H

N

H H

H

H

H polymer

+

H

+

N

H

N

H

+ H+

+

pKa = −3.8

H

H

CCH 3

O

CCH 3

O

N

H

N

H

CH 3 COCCH 3

O

+ + CH 3 COH

O O

O

CH 3 CCl

O

+

O

+ HCl

2-acetylpyrrole

2-acetylfuran

1. BF 3


2. H 2 O
   
   
   1. SnCl 4
   
   
   2. H 2 O CCH 3
   
   
   
   

O

S

CH 3 CCl

O

+

S

+ HCl

1. AlCl 3


2. H 2 O

O

+ CH 3 CCl + HCl

O

CCH 3

2-acetylthiophene

phenylethanone

BF 3 ,

SnCl 4 ,

AlCl 3 ,