Isoquinoline is a heterocyclic aromatic organic compound and structural isomer of quinoline, first isolated from coal tar in 1885. It possesses unique physical properties, including being a colorless hygroscopic liquid with a low solubility in water, and serves as a structural backbone in naturally occurring alkaloids. Isoquinoline has various medicinal uses, including applications in treating high blood pressure and as an anesthetic.

1. Fused Heterocyclic compound
ISOQUINOLINE
Lecture by
S.Mathivanan., M.pharm
Asst Professor
Pharmacy

2. Isoquinoline is a heterocyclic aromatic organic
compound. It is a structural isomer of quinoline.
Isoquinoline and quinoline are benzopyridines,
which are composed of a benzene ring fused to
a pyridine ring.
Other names
Benzo[c]pyridine
2-benzazine

3. Production
• Isoquinoline was first isolated from coal tar in
1885 by Hoogewerf and van Dorp.
• They isolated it by fractional crystallization of the
acid sulfate.
• Weissgerber developed a more rapid route in
1914 by selective extraction of coal tar, exploiting
the fact that isoquinoline is more basic than
quinoline.
• Isoquinoline can then be isolated from the
mixture by fractional crystallization of the acid
sulfate.

4. The structural backbone in naturally
occurring alkaloids including papaverine.

5. Physical properties
• Isoquinoline is a colorless hygroscopic liquid
• Unpleasant odour
• Impure samples can appear brownish,
• It crystallizes in platelets that have a low solubility in water but
dissolve well in ethanol, acetone, diethyl ether, carbon
disulfide, and other common organic solvents.
• It is also soluble in dilute acids as the protonated derivative.
• Density1.099 g/cm3
• Melting point26–28 °C
• Boiling point242 °C

6. Properties
1. Aromatic
Being an analog of pyridine, isoquinoline is a weak base, with a pKa of
5.14. It protonates to form salts upon treatment with strong acids, such
as HCl

7. • In isoquinoline all ring atoms (9 carbons and 1
nitrogen) are SP2 hybridized.
• Two SP2 orbitals on each atom overlap with each
other to form the C-C and C-N σ bonds. The third
SP2 orbital on each carbon atom overlaps with an
S orbital of hydrogen and forms C-H σ bonds.
• The third SP2 orbital of nitrogen is occupied by
the nitrogen lone pair of electrons.
• Each ring atom possess one un hybridized p –
orbital containing one electron and those are
perpendicular to the plane containing the σ
bonds.

8. • Overlap of these p – orbitals produces delocalized π –
molecular orbital containing 10 electrons.
• Isoquinoline shows aromatic properties because the resulting
molecular orbital satisfies the Huckle’s rule (4n+2 rule).
• The nitrogen lone pair is not released into the aromatic
system because it is perpendicular to the π system.
• The nitrogen withdraws electrons by resonance, resulting in
an electron-deficient ring system.

9. Synthesis
1. Bischler-Napieralski Isoquinoline synthesis

10. Bischler Napieralski reaction Mechanism

11. Synthesis
2. The Pictet – Gams synthesis

12. Synthesis
3. Pomeranz–Fritsch synthesis

14. Reactions
1. Electrophilic addition to N

15. Reactions
2. Electrophilic aromatic substitution

16. Reactions
3. Reduction reactions

17. Reactions
4. Oxidation

18. Reactions
5. Nucleophilic substitution

19. Medicinal uses

20. • Quinapril : used to treat high blood
pressure, heart failure, and diabetic kidney
disease

21. Medicinal uses

22. • Dimethisoquin : Anaesthetic

23. Thank you students..!!!
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