1. HETEROCYCLES
• Monocyclic or fused rings
• Cont. one ore more ring atom ≠ C
(normally O; N; S)
• Aromatic and non-aromatic

2. Heterocyclic Aromatic Compounds
 Example of aromatic heterocyclic compounds are
shown below
 Numbering always starts at the heteroatom
2

3.  6-Membered rings (Heteroatom N)
N
PyridineOther examples
N
Quinoline
N
N
Pyrimidine
N
N
Pyridazine
Rare in nature
N
N
Pyrazine
N
N
H
NH2
O
Cytosine
N
Quinine
H3CO
HO
N
N
Ant pheremone
N
N
Hydralazine
Antihypertensive drug
H2NHN

4. Pyridine has an sp2
hybridized nitrogen
 The p orbital on nitrogen is part of the aromatic
system of the ring
 The nitrogen lone pair is in an sp2 orbital
orthogonal to the p orbital of the ring; these
electrons are not part of the aromatic system
 The lone pair on nitrogen is available to react with
protons and so pyridine is basic

5. Pyridine as a base
N N
H
+ H
kebasaan piridin (pKb=8,75) < kebasaan amina
alifatik (pKb=+4)
karena
elektron menyendiri berada dalam orbital sp2
bukan orbital sp3
N
HCl
CH3I
NH Cl
+ _
NCH3 I
+ _
menjalani reaksi khas
amina

6. ELECTROPHILIC SUBSTITUTION
6-membered rings
- N more electronegative than C
- electron deficient in ring
(atom C mengemban muatan positif parsial)
- reactivity in electrophilic substitution
(dibandingkan dengan benzena)
N N N N N

7. N
N
E
N
H
E
N
E
+ E
+ res. forms
•Both C and N may react
•3/5 pos. most reactive C
•Not Friedel-Crafts reaction
•Not coupling wit diazonium
•Sulfonation, Nitration, Halogenation
(brominasi berlangsung hanya pada
temperatur tinggi dalam fase uap,
melalui mekanisme radikal bebas)
N N
H
N
H
H NO2
N
NO2
H / NO2 H / NO2
+ res. forms
Benzo ring most reactive
Much slower react. than naphthalene

8. OKSIDASI
CH3
CO2H
KMnO4
kalor
N
N
CH3
CO2H
KMnO4
kalor

9. 6-membered rings (N menarik rapatan elektron dari cincin)
N Cl
OMe
N
OMe
Cl
+ res. form
N OMe
2 / 4 Pos. reactive; electron def. C, neg. charge partly on N in interm
3 / 5-Pos. much less reactive (benzenoid pos.)
Nucleophilic Substitution
X Nu X
Nu
X
Nu
X
Nu
Nu

10. + NH2
_
100o
C
N
+ NH2
_
100o
C
-H2O
N NH
_
N NH2
H2O

11. N
N
HNO3
H2SO4
0o
C
HNO3
H2SO4
0o
C
kuinolina
isokuinolina
N N
+
NO2
NO2
N N
+
NO2
NO2
•merupakan basa lemah
•menjalani substitusi elektrofilik lebih mudah daripada piridin
•substituen masuk pada posisi 5 dan 8

12. N
N
kuinolina
isokuinolina
N
N
NH2
CH3
NH2
_
H2O
CH3Li
H2O
Substitusi nukleofilik
terjadi pada posisi 2 terhadap nitrogen

13.  5-Membered rings (Heteroatom N, O, S)
S
Thiophene
N
H
Pyrrole
O
Thiophene
Other examples
N
N
H
Imidazole
N
S
Thiazole
N
H
Indole
N
H
R'' NHR
R'
R=H
R'=CO2H
R'''=H
Tryptophane
R=H
R'=H
R'''=OH
Serotonin
R=Ac
R'=H
R'''=OCH3
Melatonin
N
N
H
N
N
NH2
Adenine
(purine der.)
N
N
H
H2N
R
R=CO2H: Histidine
R=H: Histamine
N
S
N
N
H3C
HO
H2N
CH3
Thiamin
(Vit B1)

14. The nitrogen in pyrrole is sp2 hybridized
and the lone pair resides in the p orbital
This p orbital contains two electrons and
participates in the aromatic system
The lone pair of pyrrole is part of the
aromatic system and not available for
protonation; pyrrole is therefore not basic
Chapter 14 14

15.  In furan and thiophene an electron
pair on the heteroatom is also in a
p orbital which is part of the
aromatic system

16. 5-membered rings - electron rich
X
+ E
X
E
H X
E
H X
E
H X E
X
+ E
X
E
H
X
E
H
X E
React. in -position generally preferred, more
resonance structures
React.: Pyrrole > thiophene > furan
•karena atom N menyumbang 2 elektron ke awan
pi aromatik, atom N menjadi deficient electron,
tidak bersifat basa
•cincin kaya elektron

17. N
H
N
H
N
H
SO3H
NO2
SO3
piridin
HNO3
(CH3CO)2O
SUBSTITUSI ELEKTROFILIK
tidak menjalani reaksi substitusi nukleofilik

18. Nucleosides, Nucleotides, Nucleic acids (DNA; RNA)
DNA bases
DNA Nucleosides
2-Deoxyribosides
RNA bases
HN
N
O
O
Thymidine
N
N
NH2
O
Deoxycytosine Deoxyadenosine
N
N N
N
NH2
HN
N N
N
O
H2N
O O O O
OH OH OH OH
HO HO HO HO
Deoxyguanoosine
HN
N
H
O
O
Thymin
N
N
H
NH2
O
Cytosin Adenine
N
N N
H
N
NH2
Guanine
HN
N N
H
N
O
H2N
HN
N
H
O
O
Uracil
Cytosin Adenine Guanine
RNA Nucleosides
Ribosides
HN
N
O
O
Urinine
Cytosine
Adenosine
O
OH
HO
Guanoosine
OH

19. Nucleotides
O
O
XHO
B
P
O
O
XO
B
P
O
O
O
HO
XO
B
O
O
5'
3'
Double -helix
(DNA)
A-T and G-C Base pairs
N
N
O
O CH3
HN
N
N H
H
N
N
N
N
O
N
N
N
O
N
N
H
N
H
H
H
H

20. PORFIRIN
A : cincin pirol
B : cincin porfirin
C : protoporfirin IX

22. ALKALOID :
senyawa yang diambil dari jaringan
tumbuhan yang mengandung nitrogen dalam
strukturnya dan larut dalam air
 nikotina
 morfina
 kodeina
 heroin
 dekstrometorfa
n
 atropina
 skopolamina
 kokaina