+ + + + X

14. HETEROCYCLIC COMPOUNDS
Homocyclic -Contains only carbon atoms in the cyclic
Heterocyclic -Contains carbon atoms and atoms other than
carbon
Properties -Similar to the open chain analogs, except for the
small ring systems
Heterocyclic compounds in nature

14.1 THREE-MEMBERED RING HETEROCYCLES
-Structures and Properties
H
N
O
S
H
N
O
NH
NH
Aziridine Oxirane Thiirane Diaziridine Oxaziridine
H
N
N
O
S
N
O
N N
2-Azirine 1-Azirine Oxirene Thiirene Diazirine Oxazirene

-Nomenclature
The heteroatom will be set at the lowest position.
Priority is : O, S, N
-Chemical Properties
Follow the open chain analogs, except for the ring strain which
causing ring cleavage.
-Preparation
From ethanolamine and derivatives
Addition of carbene to double bond
Peracid oxidation to double bond
Darzens reaction of carbonyl and α-chloroesters
Thiocyanates and oxirane etc.

-Some Natural Occuring and Interesting Compounds
O
O
(Anti certain cancer
tumers in rats)
O
O
(Antibiotic)
O
O
MeO
Auraptin
O
O
O
MeO
O
CH 2 OCONH 2
OMe
Me
N NH
O
Mitomycin A (Antibiotic and
posseses anticancer activity)
O Me
Me
O
OCO(CH=CH) 4 COOH
Fumagillin (Antibiotic)
Me

14.2 FOUR-MEMBERED RING HETEROCYCLES
-Structures and Properties
NH O S NH
NH
O
O
Azetidine Oxetane Thietane 1,2-Diazetidine 1,2-Dioxetane
S
NH
NH
NH
S
O
S
1,2-Dithietane Oxazetidine Thiazetidine
HN
1,3-Diazetidine
S
O S S
S
S
1,3-Dithietane Oxetene Thietene Dithietene

-Chemical Properties
Follow the open chain analogs, except for the ring
-Preparation
Halocompounds of N, O, S
Cycloaddition of carbonyl and double bond etc.
-Some Natural Occuring and Interesting Compounds
H H
RHN
N
O
HOOC
S
Me
Me
H
RHN
COOH
R = PhCH 2
CO- (Penicillin G) R = HOOCCH(NH 2
)CH 2
CH 2
CO-
R = PhOCH 2
CO- (Penicillin V) (Cephalosporin C)
O
N
S
CH 2 OAc

14.3 FIVE-MEMBERED RING HETEROCYCLES
-Structures and Properties
X • •
5
4
X 1 X = NH, Pyrrole
2 X = O, Furan
X = S, Thiophene
3
+ + + +
X X X
-
-
X
-
-
5
6
4
7
3
X
1
2
X = NH,
X = O,
X = S,
Indole
Benzofuran
Benzo[b]thiophene

5
4
X 1 2
3
X = NH, 2,3-Dihydropyrrole (Δ 2 -pyrroline)
X = O, 2,3-Dihydrofuran
X = S, 2,3-Dihydrothiophene
5
4
X 1 2
3
X = NH, Tetrahydropyrrole (pyrrolidine)
X = O, Tetrahydrofuran
X = S, Tetrahydrothiophene
-Chemical Properties
Follow the monosubstituted benzenoid compounds
E
H
+
X
E +
X • •
X • •
E +
+
X
H
E

-Preparation
-From coal tar, from plants e.g. Oat
-Synthesis via Knorr, Hantzsch, Feist’s, Fischer,
-Medelung, Bischler’s, and Nenitzsecu syntheses, etc.
-Some Natural Occuring and Interesting Compounds
For examples Cyanocobalamin (Vitamin B 12
)
Chlorophyll (Green plant pigment)
Heme (Oxygen carrier)
Copper phthalocyanine (A blue pigment)
Reserpine (A transquilizing drug)
Biotin (A growth factor for yeast)
Thiamine (Vitamin B 1
)

Me
ROOC
Me
COOMe
N
Me
An ant trail marker
Me N
H
The Colombian arrow poison
N
Nicotine
O
N
Me
H
N
HN
CONEt 2
N
Me
Lysergic diethylamine
(LSD, An hallucinogen)
N
H
O
Indigo (A dye)

O
S
HO
O
O
Thioindigo (A dye)
Me
O
S
N
N
Ph
Antipyrine (An
antipyretic drug)
Ph
Me
Me
O
A flavor component of pineapple
S
NHSO 2
NH 2
N
Sulphathiazole
H 2 NCH 2 CH 2
N
N
Histamine
H

14.4 SIX-MEMBERED RING HETEROCYCLES
-Structures and Properties
6
5
X 1 2
4
3
X = N, Pyridine
X = O + , Pyrylium cation
X = S + , Thiapyrylium cation
-Chemical Properties
Follow the monosubstituted benzenoid compounds
-Preparation
From coal tar and plants

-Some Natural Occuring and Interesting Compounds
For examples
Quinine (An antimalarial agent)
D-γ-Tocopherol (Vitamin E)
Thiamine (Vitamin B 1
)
Riboflavin (Vitamin B 2
)
Sulphadiazine (An antibacterial agent)
Coenzyme A (A cofactor)

COOH
CONH 2
HO
CH 2 OH
CH 2 OH
N
N
Me N
Niacin Nicotinamide Pyridoxine (Vitamin B 6
)
N
Coramine
CONEt 2
HO
O
NMe
NH 2
N
NHSO 2
Sulphapyridine
HO
Morphine