Contents includes at least three strategies of synthesis for each of three, four, five and six membered heterocylic ring with one or two heteroatoms. One mechanism described out of the three strategies. Few name reactions are described and the other are simple synthetic methods. This presentation was prepared for the partial fulfillment of Master of Pharmacy. The content was taken from the various books, mentioned in slide with the title of references.
Unit iii heterocyclic compounds as per PCI Syllabus of POC-IIIGanesh Mote
Nomenclature of hetero cyclic compounds, classification of heterocyclic compounds, Reactivity, aromaticity, orbital picture, stability, resonance energy, resonance structure, basicity, method of preparation, reaction and medicinal uses of Pyrrole, furan and thiophene
Contents includes at least three strategies of synthesis for each of three, four, five and six membered heterocylic ring with one or two heteroatoms. One mechanism described out of the three strategies. Few name reactions are described and the other are simple synthetic methods. This presentation was prepared for the partial fulfillment of Master of Pharmacy. The content was taken from the various books, mentioned in slide with the title of references.
Unit iii heterocyclic compounds as per PCI Syllabus of POC-IIIGanesh Mote
Nomenclature of hetero cyclic compounds, classification of heterocyclic compounds, Reactivity, aromaticity, orbital picture, stability, resonance energy, resonance structure, basicity, method of preparation, reaction and medicinal uses of Pyrrole, furan and thiophene
Heterocyclic chemistry - Fused ring systemsNaresh Babu
Fused hetero cyclic ring systems like Quinoline, Isoquinoline, Indole, Acridine, Benzimidzole & Phenothiazine - Structure, Aromaticity, Preparations, Acidity-Basicity and characteristic chemical reactions
Introduction of poly-cyclic compounds, resonance, molecular orbital structure, physical properties, preparation, reaction and uses of napthalene, anthracene, phenanthrene, napthaquinone, napthol, napthylamine, 9,10 anthraquinone and phenanthrequinone.
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
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
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
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
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