Chapter 43 — Aromatic heterocycles: structures and
reactions
-  Introduction to heterocycles
-  Pyridine basicity and reactivity, and DMAP catalysis of
acylations (1147–53)
- Pyrrole and furan: where’s the lone pair? (1157–61)
- Imidazoles, pyrazoles, triazoles, tetrazoles (1165–69)
- Benzo-fused heterocycles: indoles (1169–71), quinolines
(1174–75)
- FOOD: coffee skullduggery and decaffeination processes
Heterocyclic drugs
Celebrex (Pfizer)
Lornoxicam (Pozen)
Gleevec (Novartis)
O
N
H
O
O
O
N
NH
N N
Pranlukast (Ono Japan)
Viagra (Pfizer)
Levitra (GSK/Bayer)
Reminder on orbitals
Atoms in small aromatic rings are almost always sp2 hybridized
1s
3p
3 sp2
1p
Pyridine’s nitrogen is an imine-type functional group
- Bad at stabilizing positive charges by resonance donation
Br2
Br
+ Br–
N
N
- Good at stabilizing negative charges by resonance accepting
Nu
+ Cl–
N
Cl
N
Nu
Pyrrole’s nitrogen is an enamine-type functional group
- Good at stabilizing positive charges by resonance donation
H
N
Br2
Br
Br
H
N
Br
Br
- Bad at stabilizing negative charges by resonance accepting
Cl
H
N
Nu
Nu
H
N
Furans are electron-rich, and are good nucleophiles
like pyrroles
O
Br2
Br
O
Br
O
Ac2O, ZnCl2
O
Br
Br
O
HNO3
O2N
O
O
Azoles: 5-membered nitrogen rings with 2, 3, 4, or 5
heteroatoms
H
N
N
H
N
H
N
N
N
N
imidazole
pyrazole
O
N
oxazole
1,2,3-triazole
S
N
thiazole
H
N
N
N N
tetrazole
Benzo-fused heterocycles
H
N
N
N
N
N
H
Indole
Benzimidazole
N
H
N
Benzotriazole
Quinoline
O
Et2N
N
H
N
H
Quinine
Lysergic acid diethylamide